A Phase 1/2 Study of CPI-0610 With and Without Ruxolitini... | NCT02158858

ID	Type	Description	Link
2018-000579-34	EudraCT Number
CDAK539A12201	Other Identifier	Novartis

Name	Class
The Leukemia and Lymphoma Society	OTHER

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase 1	Experimental	Patients were enrolled in sequential cohorts (acute leukemia, including acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and acute undifferentiated or biphenotypic leukemia; chronic myelogenous leukemia (CML) in blast crisis; myelodysplastic syndrome (MDS); myelodysplastic/myeloproliferative neoplasms (MDS/MPN); or myelofibrosis (MF)) and received escalating doses of pelabresib (CPI-0610).	Drug: Pelabresib
Phase 2 (Arm 1): Prior JAKi Monotherapy Arm (MF patients treated with pelabresib alone)	Experimental	Cohort 1A: Was open to patients with MF who were Transfusion Dependent (TD) and who had previously been treated with a JAKi and were intolerant, resistant, refractory, or had lost response to the JAKi, or were ineligible to be treated with a JAKi (pelabresib (CPI-0610) alone). Cohort 1B: Was open to patients with MF who were not TD and who had previously been treated with a JAKi and were intolerant, resistant, refractory, or had lost response to the JAKi, or were ineligible to be treated with a JAKi (pelabresib (CPI-0610) alone).	Drug: Pelabresib
Phase 2 (Arm 2): Prior JAKi Combination Arm	Experimental	Cohort 2A: Was open to patients with MF who were Transfusion Dependent (TD) and were taking ruxolitinib but had disease that was not adequately controlled by ruxolitinib (pelabresib (CPI-0610) + Ruxolitinib). Cohort 2B: Was open to patients with MF who were not TD and were taking ruxolitinib but had disease that was not adequately controlled by ruxolitinib (pelabresib (CPI-0610) + Ruxolitinib).	Drug: Pelabresib Drug: Ruxolitinib
Phase 2 (Arm 3): JAKi Naïve Combination Arm

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pelabresib	Drug	CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)	Phase 1 Phase 2 (Arm 1): Prior JAKi Monotherapy Arm (MF patients treated with pelabresib alone)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase 1: Frequency of Dose-limiting Toxicities (DLTs)	A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed by the Investigator as unrelated to disease progression, intercurrent illness, or concomitant medications that occurred within the first cycle of treatment (21-day cycle) with pelabresib (CPI-0610), and that met any of the criteria specified in the protocol.	Up to 21 days
Phase 2 (Cohorts 1B, 2B, and Arm 3): Number of Participants With Splenic Response Rate (SVR35) at Week 24	Splenic Response Rate (SVR35) at Week 24 was defined as the proportion of participants who demonstrated a reduction of at least 35% in spleen size from baseline, as measured by imaging techniques (MRI or CT), following 24 weeks of treatment.	Week 24 (Cycle 9 Day 1)
Phase 2 (Cohorts 1A and 2A): Number of Participants Enrolled as Transfusion Dependent (TD) With Conversion Rate From Red Blood Cell (RBC) Transfusion Dependence (TD) to Transfusion Independence (TI)	Conversion rate was defined as the proportion of participants who converted from transfusion dependence (TD) to transfusion independence (TI). TD was characterized by receiving an average of at least 2 units of red blood cell (RBC) transfusions per month-amounting to a minimum of 6 units over the 12 weeks prior to enrollment-while TI was defined as the absence of RBC transfusions during any consecutive 12-week period.	Any 12 consecutive weeks (rolling window) during active treatment with pelabresib (CPI-0610), from first dose through treatment discontinuation (up to approximately 8 years for Phase II)
Phase 2 (Arm 4): Number of Participants With Complete Hematological Response (CHR) Rate	Complete Hematological Response (CHR) Rate was defined as the proportion of participants who fulfilled the criteria for CHR, based on the modified European LeukemiaNet (ELN) guidelines (Barosi et al 2009): platelet count ≤400 × 10⁹/L, white blood cell (WBC) count ≤10 × 10⁹/L, confirmation of laboratory values after one treatment cycle, and normal spleen size determined by palpation or imaging.

Secondary Outcomes

Measure	Description	Time Frame
Phase 1: Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria	The distribution of adverse events was performed through the analysis of frequencies for treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs), based on the monitoring of relevant clinical and laboratory safety parameters. Treatment-emergent adverse events (TEAEs) in this study were defined as events that began after the first dose of study treatment and continued until 30 days after the last dose, or events that were present prior to the first dose and increased in severity based on preferred term within 30 days following the last dose of pelabresib (CPI-0610).

Eligibility Module

Eligibility Criteria

Phase I (Dose Escalation) - Inclusion and Exclusion Criteria:

Inclusion Criteria (Phase I):
- Age: Adults ≥18 years.
- Diagnosis: Histologically or cytologically confirmed diagnosis of one of the following hematologic malignancies:
  - Acute myelogenous leukemia (AML)
  - Acute lymphocytic leukemia (ALL)
  - Acute undifferentiated or biphenotypic leukemia
  - Chronic myeloid leukemia (CML) in blast crisis
  - Myelodysplastic syndrome (MDS)
  - Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
  - Myelofibrosis (MF)
- Performance Status: ECOG ≤2.
- Organ Function:
  - Serum total bilirubin ≤1.5 × ULN
  - AST/ALT ≤2.5 × ULN (up to 5 × ULN if due to leukemic infiltration)
  - Serum creatinine ≤2.0 × ULN or CrCl ≥30 mL/min
- Hematology (MF only):
  - Platelet count ≥50 × 10⁹/L and ANC ≥1 × 10⁹/L (MF not on ruxolitinib)
  - Platelet count ≥75 × 10⁹/L and ANC ≥1 × 10⁹/L (MF on ruxolitinib)
- Other:
  - DIPSS-plus risk category of intermediate-2 or high (MF only)
  - Serum glucose ≤160 mg/dL (or HbA1C ≤7%)
  - Fully recovered from major surgery and acute toxic effects of prior therapy
  - Negative pregnancy test for women of childbearing potential
  - Agreement to use appropriate contraception
  - Written informed consent
Exclusion Criteria (Phase I):
- Untreated newly diagnosed acute leukemia (unless AML with myelodysplasia-related changes and 20-30% blasts)
- Relapsed/refractory acute leukemia where further induction chemotherapy is beneficial
- Acute leukemia relapse <6 months after allogeneic SCT
- CML in blast crisis treated with only one TKI
- Very low/low risk MDS without prior treatment
- CNS involvement by leukemia (unless resolved)
- Active HIV, Hepatitis B or C infection
- GI impairment affecting absorption (unresolved nausea, vomiting, diarrhea >CTCAE grade 1)
- Significant cardiac disease (recent MI/angina, high cTn, QTcF >470 ms, LVEF <50%, uncontrolled arrhythmia, etc.)
- Severe/uncontrolled comorbidities
- Recent systemic anti-cancer therapy (other than hydroxyurea/radiotherapy) <2 weeks prior
- Ongoing or recent JAK inhibitor use (<2 weeks prior, MF only)
- Recent therapeutic antibody (<4 weeks) or investigational agent (<2 weeks or <5 half-lives)
- Use of strong CYP450 inhibitors/inducers or drugs with Torsades de Pointes risk
- Immunosuppressive treatment that cannot be discontinued
- Pregnant/lactating women
- Inadequate contraception
- Inability/unwillingness to comply with protocol

Phase II (Expansion) - Inclusion & Exclusion Criteria:

Inclusion Criteria (Phase II):
1. MF Arms (Prior JAKi, Add-on JAKi, JAKi Naïve)
  - Age: Adults ≥18 years
  - Diagnosis: Confirmed primary MF or MF evolved from ET or PV
  - Risk: DIPSS intermediate-2 or higher
  - Platelets:
    - ≥75 × 10⁹/L (Arms 1 & 2)
    - ≥100 × 10⁹/L (Arm 3, JAKi naïve)
  - ANC: ≥1 × 10⁹/L
  - Spleen Volume: ≥450 cm³ by MRI/CT (non-TD cohorts) OR
  - Transfusion Dependence: Average ≥2 RBC transfusions/month (total ≥6 in prior 12 weeks) for TD cohorts
  - Peripheral Blood Blasts: <10%
  - Symptoms: At least 2 symptoms measurable (score ≥1 for Arms 1 & 2; score ≥3 or total ≥10 for Arm 3) using MFSAF v4.0
  - Treatment History:
    - Arm 1 (Prior JAKi): Previously treated with JAKi and intolerant, resistant, refractory, or lost response, or ineligible for JAKi
    - Arm 2 (Add-on JAKi): On ruxolitinib ≥6 months, stable dose ≥8 weeks, not adequately controlled
    - Arm 3 (JAKi Naïve): No prior JAKi, eligible for ruxolitinib
  - Performance Status: ECOG ≤2
  - Organ Function: Serum direct bilirubin <2 × ULN, AST/ALT ≤2.5 × ULN (up to 5 × ULN if due to liver involvement), CrCl ≥45 mL/min
  - Other: Fully recovered from major surgery/acute toxic effects, effective contraception, written informed consent
2. ET Arm (High-Risk ET)
  - Age: Adults ≥18 years
  - Diagnosis: Confirmed ET (WHO 2016 criteria)
  - High-Risk: At least one of:
    - Age >60 years
    - Platelets >1500 × 10⁹/L
    - Prior thrombosis, erythromelalgia, or migraine (disease-related)
    - Prior hemorrhage related to ET
    - Diabetes/hypertension requiring therapy >6 months
  - Symptoms: ≥2 symptoms with average score ≥3 or total score ≥15 (MPN-SAF)
  - Platelets: >600 × 10⁹/L
  - Resistant/Intolerant to HU: As defined by ELN
  - Performance Status: ECOG ≤2
  - Life Expectancy: >24 weeks
  - ANC: ≥1 × 10⁹/L
  - Organ Function: Serum direct bilirubin <2 × ULN, AST/ALT ≤2.5 × ULN, CrCl ≥45 mL/min
  - Other: Fully recovered from major surgery/acute toxic effects, effective contraception, written informed consent
Exclusion Criteria (Phase II)
- Prior splenectomy (MF non-TD cohorts)
- Splenic irradiation within 3 months
- Active or chronic HIV, Hepatitis B/C infection
- Active clinically significant infection (until recovery ≥2 weeks)
- Anemia deemed clinically significant (iron/B12/folate deficiency, hemolytic anemia)
- Major bleeding event (≥2 g/dL Hgb drop or ≥2 units transfused in last 6 months)
- Liver cirrhosis Child-Pugh B or C
- GI impairment affecting absorption (unresolved nausea, vomiting, diarrhea >CTCAE grade 1)
- Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (Arm 3)
- Hypersensitivity to ruxolitinib formulation (Arm 3)
- History of PML (Arm 3)
- Significant cardiac disease (recent MI/angina, QTcF >500 ms [>450 ms in France/Germany], uncontrolled arrhythmia, etc.)
- Ongoing uncontrolled hypertension
- Severe/uncontrolled comorbidities
- Systemic anticancer treatment (other than ruxolitinib for Arm 2, HU/ANA up to 24h prior) <2 weeks or <5 half-lives prior
- Prior treatment with any BET inhibitor
- Hematopoietic growth factor or androgenic steroids <4 weeks prior
- Systemic corticosteroids ≥10 mg prednisone equivalent within 4 weeks (exceptions for short courses)
- Concurrent/second malignancy (except certain adequately treated cancers)
- Pregnant/lactating women, or planning pregnancy within protocol-defined window
- Inability/unwillingness to comply with protocol

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic Arizona		Phoenix	Arizona	85054	United States
UCLA Medical Center

PubMed Identifier	Type	Citation	Retractions
38259250	Derived	Stein EM, Fathi AT, Harb WA, Colak G, Fusco A, Mangan JK. Results from phase 1 of the MANIFEST clinical trial to evaluate the safety and tolerability of pelabresib in patients with myeloid malignancies. Leuk Lymphoma. 2024 Apr;65(4):503-510. doi: 10.1080/10428194.2023.2300710. Epub 2024 Jan 23.
37530627	Derived

ID	Title	Description
FG000	Phase 1 (24 mg Capsule PO Daily)	Phase 1 (24 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol: Study Protocol for Phase I of the 0610-02 trial	Jan 4, 2018

Arm/Group Information

ID	Title	Description
BG000	Phase 1 (24 mg Capsule PO Daily)	Phase 1 (24 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
BG001	Phase 1 (48 mg Capsule PO Daily)	Phase 1 (48 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
BG002	Phase 1 (120 mg Capsule PO Daily)	Phase 1 (120 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
BG003	Phase 1 (170 mg Capsule PO Daily)	Phase 1 (170 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
BG004	Phase 1 (230 mg Capsule PO Daily)	Phase 1 (230 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
BG005	Phase 1 (300 mg Capsule PO Daily)	Phase 1 (300 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
BG006	Phase 1 (400 mg Capsule PO Daily)	Phase 1 (400 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
BG007	Phase 1 (225 mg Tablet PO Daily)	Phase 1 (225 mg tablet PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
BG008	Phase 1 (275 mg Tablet PO Daily)	Phase 1 (275 mg tablet PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
BG009	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
BG010	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
BG011	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2A	In Phase 2 (Arm 2) - Cohort 2A, eligible transfusion-dependent (TD) participants already on ruxolitinib received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), alongside their stable dose of ruxolitinib. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.
BG012	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2B	In Phase 2 (Arm 2) - Cohort 2B, eligible non-transfusion-dependent (non-TD) participants already receiving ruxolitinib were treated with Pelabresib 125 mg once daily for 14 days, followed by a 7-day break (21-day cycle), alongside their stable ruxolitinib dose. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.
BG013	Phase 2 - Arm 3 (Combination Treatment Arm for JAKi-Naïve MF Participants)	Eligible participants in Phase 2 (Arm 3) received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), combined with Ruxolitinib, initiated at one dose level below the recommended amount based on baseline platelet count. Dose escalation: a) Ruxolitinib: Required increase of 5 mg twice daily at Cycle 3 Day 1 if criteria were met, up to 25 mg twice daily; b) Pelabresib: Optional increase from Cycle 5 Day 1 in 25 mg steps, no more than once every two cycles, up to 175 mg once daily. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.
BG014	Phase 2 - Arm 4 (Monotherapy Arm for Essential Thrombocythemia (ET))	Eligible participants in Phase 2 (Arm 4) received Pelabresib 225 mg once daily (tablet) was administered for 14 days followed by a 7-day break (21-day cycle). No dose increases beyond 225 mg once daily were permitted. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.
BG015	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase 1: Frequency of Dose-limiting Toxicities (DLTs)

A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed by the Investigator as unrelated to disease progression, intercurrent illness, or concomitant medications that occurred within the first cycle of treatment (21-day cycle) with pelabresib (CPI-0610), and that met any of the criteria specified in the protocol.

Dose-limiting toxicity (DLT) population included all participants who received at least 85% of their planned dose of pelabresib (CPI-0610) in Cycle 1, unless interrupted by a DLT, and who had sufficient follow-up data to allow the investigators and sponsor to determine whether DLT occurred.

Posted

Count of Participants

Participants

Up to 21 days

ID	Title	Description
OG000	Phase 1 (24 mg Capsule PO Daily)	Phase 1 (24 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 1 (48 mg Capsule PO Daily)	Phase 1 (48 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG002	Phase 1 (120 mg Capsule PO Daily)	Phase 1 (120 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG003	Phase 1 (170 mg Capsule PO Daily)	Phase 1 (170 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG004	Phase 1 (230 mg Capsule PO Daily)	Phase 1 (230 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG005	Phase 1 (300 mg Capsule PO Daily)	Phase 1 (300 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG006	Phase 1 (400 mg Capsule PO Daily)	Phase 1 (400 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG007	Phase 1 (225 mg Tablet PO Daily)	Phase 1 (225 mg tablet PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG008	Phase 1 (275 mg Tablet PO Daily)	Phase 1 (275 mg tablet PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants	OG0003 OG0014 OG0025 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Primary

Phase 2 (Cohorts 1B, 2B, and Arm 3): Number of Participants With Splenic Response Rate (SVR35) at Week 24

Splenic Response Rate (SVR35) at Week 24 was defined as the proportion of participants who demonstrated a reduction of at least 35% in spleen size from baseline, as measured by imaging techniques (MRI or CT), following 24 weeks of treatment.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Week 24 (Cycle 9 Day 1)

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2B	In Phase 2 (Arm 2) - Cohort 2B, eligible non-transfusion-dependent (non-TD) participants already receiving ruxolitinib were treated with Pelabresib 125 mg once daily for 14 days, followed by a 7-day break (21-day cycle), alongside their stable ruxolitinib dose. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Primary

Phase 2 (Cohorts 1A and 2A): Number of Participants Enrolled as Transfusion Dependent (TD) With Conversion Rate From Red Blood Cell (RBC) Transfusion Dependence (TD) to Transfusion Independence (TI)

Conversion rate was defined as the proportion of participants who converted from transfusion dependence (TD) to transfusion independence (TI). TD was characterized by receiving an average of at least 2 units of red blood cell (RBC) transfusions per month-amounting to a minimum of 6 units over the 12 weeks prior to enrollment-while TI was defined as the absence of RBC transfusions during any consecutive 12-week period.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Any 12 consecutive weeks (rolling window) during active treatment with pelabresib (CPI-0610), from first dose through treatment discontinuation (up to approximately 8 years for Phase II)

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2A

Primary

Phase 2 (Arm 4): Number of Participants With Complete Hematological Response (CHR) Rate

Complete Hematological Response (CHR) Rate was defined as the proportion of participants who fulfilled the criteria for CHR, based on the modified European LeukemiaNet (ELN) guidelines (Barosi et al 2009): platelet count ≤400 × 10⁹/L, white blood cell (WBC) count ≤10 × 10⁹/L, confirmation of laboratory values after one treatment cycle, and normal spleen size determined by palpation or imaging.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Over 2 consecutive cycles (rolling window) (1 cycle = 21 days)

ID	Title	Description
OG000	Phase 2 - Arm 4 (Monotherapy Arm for Essential Thrombocythemia (ET))	Eligible participants in Phase 2 (Arm 4) received Pelabresib 225 mg once daily (tablet) was administered for 14 days followed by a 7-day break (21-day cycle). No dose increases beyond 225 mg once daily were permitted. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants	OG000

Secondary

Phase 1: Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria

The distribution of adverse events was performed through the analysis of frequencies for treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs), based on the monitoring of relevant clinical and laboratory safety parameters. Treatment-emergent adverse events (TEAEs) in this study were defined as events that began after the first dose of study treatment and continued until 30 days after the last dose, or events that were present prior to the first dose and increased in severity based on preferred term within 30 days following the last dose of pelabresib (CPI-0610).

Safety Analysis Set (SAF) included all participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Up to approximately 6 months

ID	Title	Description
OG000	Phase 1 (24 mg Capsule PO Daily)	Phase 1 (24 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 1 (48 mg Capsule PO Daily)	Phase 1 (48 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (All Arms): Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria

Safety Analysis Set (SAF) included all participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Up to approximately 387 weeks

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (All Arms): Symptom Improvement From the Patient Global Impression of Change (PGIC) at 12 and 24 Weeks

The Patient Global Impression of Change (PGIC) was a single-question, patient-reported assessment that asked individuals to rate their overall change in myeloproliferative neoplasm (MPN) symptoms since starting study treatment. The participants selected one of seven options, ranging from 'Very much improved' to 'Very much worse'. 'No Change from Baseline' indicated stable symptoms (no improvement or worsening), negative change from Baseline indicated a reduction in symptom severity (improvement), and positive change from Baseline indicated an increase in symptom severity (worsening).

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component. Only those participants contributing data at the indicated time point were analyzed.

Posted

Count of Participants

Participants

Week 12 (Cycle 5 Day 1), Week 24 weeks (Cycle 9 Day 1)

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B

Secondary

Phase 2 (Arms 1, 2 and 3): Percent Change From Baseline in Total Symptom Score (TSS) From the Myelofibrosis Symptom Assessment Form (MFSAF v4.0) at 12 and 24 Weeks

The MFSAF (Myelofibrosis Symptom Assessment Form) was completed by participants every day for 7 days before Day 1 of each treatment cycle, including the 7 days before starting Cycle 1. It used a 24-hour recall format, asking participants to rate the worst severity of seven symptoms (fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety, and bone pain) during the past 24 hours. Each symptom was rated on a scale from 0 (Absent) to 10 (Worst Imaginable). The Total Symptom Score (TSS) was the sum of 7 symptoms (range: 0-70). 'No Change from Baseline' indicated stable symptoms (no improvement or worsening), negative change from Baseline indicated a reduction in symptom severity (improvement), and positive change from Baseline indicated an increase in symptom severity (worsening).

Posted

Mean

Standard Deviation

Score on a scale

Baseline, Week 12 (Cycle 5 Day 1), Week 24 (Cycle 9 Day 1)

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (Arms 1, 2 and 3): Number of Participants Who Achieved a ≥ 50% Reduction in Total Symptom Score (TSS) at 12 and 24 Weeks

The proportion of study participants who experienced a reduction of at least 50% in their Total Symptom Score (TSS), as assessed using the Myelofibrosis Symptom Assessment Form (MFSAF v4.0), was evaluated at both 12 and 24 weeks relative to their baseline score.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Week 12 (Cycle 5 Day 1), Week 24 (Cycle 9 Day 1)

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (Arms 1, 2 and 3): Number of Participants With Overall Splenic Response Rate (Overall SVR35)

Overall Splenic Response Rate (SVR35) was defined as the proportion of participants who achieved a reduction of at least 35% in spleen size from baseline, as measured by imaging (MRI or CT), at any point between Cycle 1 Day 1 and the End of Study Visit, whichever occurred first.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through Phase II completion, an average of 6 years

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (Arms 1, 2 and 3): Duration of Overall Splenic Response (Overall SVR35)

Duration of Overall Splenic Response (overall SVR35) was defined as the time from the first occurrence of a at least 35% reduction in spleen volume from baseline until the earliest of the following: a reduction of less than 35% from baseline combined with an increase of more than 25% from the nadir in spleen volume (as measured by MRI or CT), or death. The nadir was defined as the lowest spleen volume recorded after baseline and up to the evaluation point at which the initial splenic response was achieved.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Median

95% Confidence Interval

Weeks

From first onset of splenic response until loss of response, assessed up to approximately 6 years

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (Cohorts 1A and 2A): Number of Participants With Splenic Response Rate (SVR35) at 12 and 24 Weeks

Splenic Response Rate (SVR35) at 12 and 24 weeks was defined as the proportion of participants who achieved a reduction of at least 35% in spleen size from baseline, as determined by imaging (MRI or CT), following 12 and 24 weeks of treatment, respectively.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Week 12 (Cycle 5 Day 1), Week 24 weeks (Cycle 9 Day 1)

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2A	In Phase 2 (Arm 2) - Cohort 2A, eligible transfusion-dependent (TD) participants already on ruxolitinib received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), alongside their stable dose of ruxolitinib. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (Cohorts 1A and 2A): Duration of Red Blood Cell (RBC) Transfusion Independence (TI) in Participants Who Enroll as Transfusion Dependent (TD)

Duration of Red Blood Cell (RBC) Transfusion Independence (TI) was defined as the longest continuous period during which participants, having achieved at least 12 weeks of transfusion independence, remained free from RBC transfusions.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Median

Full Range

Weeks

From first onset of TI to earliest onset of loss of TI, assessed up to approximately 6 years

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2A	In Phase 2 (Arm 2) - Cohort 2A, eligible transfusion-dependent (TD) participants already on ruxolitinib received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), alongside their stable dose of ruxolitinib. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (Cohorts 1A and 2A): Early Anemic Response Rate in Participants Who Enroll as Transfusion Dependent (TD)

Early anemic response rate was defined as the proportion of participants who achieved an average increase of at least 1 g/dL in hemoglobin concentration over any rolling 8-week (56-day) period following baseline. This calculation was performed after applying the 14/3 day rule, which stipulates that hemoglobin measurements must be spaced at least 14 days apart, and that at least 3 such measurements are required within the 8-week window to ensure a reliable average. Importantly, this increase had to occur without any red blood cell (RBC) transfusions during the treatment period and up to the time of the latest hemoglobin assessment for each patient.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through Phase II completion, an average of 6 years

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2A

Secondary

Phase 2 (Cohorts 1B, 2B, and Arm 3): Number of Participants With Splenic Response Rate (SVR35) at 12 Weeks

Splenic Response Rate (SVR35) at Week 12 was defined as the proportion of participants who achieved a reduction of at least 35% in spleen size from baseline, as measured by imaging (MRI or CT), following 12 weeks of treatment.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Week 12 (Cycle 5 Day 1)

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2B	In Phase 2 (Arm 2) - Cohort 2B, eligible non-transfusion-dependent (non-TD) participants already receiving ruxolitinib were treated with Pelabresib 125 mg once daily for 14 days, followed by a 7-day break (21-day cycle), alongside their stable ruxolitinib dose. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (Cohorts 1B, 2B, and Arm 3): Anemic Response Rate in Participants Who Enroll as Non-transfusion-dependent (Non-TD)

Anemic response was defined as a sustained average increase in hemoglobin concentration of at least 1.5 g/dL over any rolling 12-week (84-day) period following baseline. This calculation excluded periods involving red blood cell (RBC) transfusions and was performed after applying the 14/3-day rule for valid hemoglobin assessments. The response had to be maintained through to the most recent available hemoglobin measurement for each patient.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through Phase II completion, an average of 6 years

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2B	In Phase 2 (Arm 2) - Cohort 2B, eligible non-transfusion-dependent (non-TD) participants already receiving ruxolitinib were treated with Pelabresib 125 mg once daily for 14 days, followed by a 7-day break (21-day cycle), alongside their stable ruxolitinib dose. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (Arm 4): Percentage of Participants Who Achieve a ≥50% Reduction From Baseline in the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Score

The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) is a patient-reported questionnaire designed to measure symptom burden in participants with myeloproliferative neoplasms (MPNs). Participants rate the severity of several symptoms (such as fatigue, night sweats, itching, abdominal discomfort, bone pain, early satiety, and others) over the past 24 hours. Each symptom is scored on a scale from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be). The total score is the sum of all individual symptom scores, providing an overall measure of symptom burden. A 50% reduction in the MPN-SAF total score at 12 or 24 weeks means the patient's overall symptom burden has improved by half compared to their baseline (pre-treatment) score.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Baseline, 12 weeks (Cycle 5, Day 1), 24 weeks (Cycle 9, Day 1)

ID	Title	Description
OG000	Phase 2 - Arm 4 (Monotherapy Arm for Essential Thrombocythemia (ET))	Eligible participants in Phase 2 (Arm 4) received Pelabresib 225 mg once daily (tablet) was administered for 14 days followed by a 7-day break (21-day cycle). No dose increases beyond 225 mg once daily were permitted. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (Arm 4): Partial Hematological Response Rate (PHR)

Partial Hematological Response Rate (PHR) was defined as the proportion of participants who met the following criteria over two consecutive cycles up to the last administration of study treatment:

Platelet count > 400-600 x 10^9/L
WBC count within normal range (i.e., ≤ 10 x 10^9/L)
Laboratory results confirmed after 1 cycle (after 3weeks)

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Over 2 consecutive cycles (rolling window) (1 cycle = 21 days)

ID	Title	Description
OG000	Phase 2 - Arm 4 (Monotherapy Arm for Essential Thrombocythemia (ET))	Eligible participants in Phase 2 (Arm 4) received Pelabresib 225 mg once daily (tablet) was administered for 14 days followed by a 7-day break (21-day cycle). No dose increases beyond 225 mg once daily were permitted. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants	OG000

Secondary

Phase 2 (Arm 4): Overall Hematological Response Rate (OHR)

Confirmed Overall Hematological Response (OHR) Rate was defined as the proportion of participants with either a confirmed complete or a partial hematological response at any time.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through Phase II completion, an average of 6 years

ID	Title	Description
OG000	Phase 2 - Arm 4 (Monotherapy Arm for Essential Thrombocythemia (ET))	Eligible participants in Phase 2 (Arm 4) received Pelabresib 225 mg once daily (tablet) was administered for 14 days followed by a 7-day break (21-day cycle). No dose increases beyond 225 mg once daily were permitted. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants	OG000

Secondary

Phase 2 (Arm 4): Duration of Overall Hematological Response Rate (OHR)

Duration of Overall Hematological Response (OHR) Rate was defined as the time from when the overall hematological response was first met until the time at which the overall hematological response was lost, i.e., the criteria for an overall hematological response (CHR or PHR) were not observed or death occurred, whichever came first.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Median

95% Confidence Interval

Weeks

Through Phase II completion, an average of 6 years

ID	Title	Description
OG000	Phase 2 - Arm 4 (Monotherapy Arm for Essential Thrombocythemia (ET))	Eligible participants in Phase 2 (Arm 4) received Pelabresib 225 mg once daily (tablet) was administered for 14 days followed by a 7-day break (21-day cycle). No dose increases beyond 225 mg once daily were permitted. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants	OG000

Secondary

Phase 2 (Arm 4): Rate of Hemorrhagic and Thromboembolic (TE) Events

Rate of hemorrhagic and thromboembolic (TE) events was defined as the proportion of participants with hemorrhagic or thromboembolic events throughout the study.

Intent-to-Treat (ITT) set: all screened participants who have received at least 1 dose of any study treatment component.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through Phase II completion, an average of 6 years

ID	Title	Description
OG000	Phase 2 - Arm 4 (Monotherapy Arm for Essential Thrombocythemia (ET))	Eligible participants in Phase 2 (Arm 4) received Pelabresib 225 mg once daily (tablet) was administered for 14 days followed by a 7-day break (21-day cycle). No dose increases beyond 225 mg once daily were permitted. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants	OG000

Secondary

Phase 2 (All Arms): Maximum Observed Plasma Concentration (Cmax) of Pelabresib

Pharmacokinetic (PK) parameters were calculated based on Pelabresib plasma concentrations and actual sampling time points.

Cmax was listed and summarized using descriptive statistics.

PK analysis set (PKAS): all participants in the ITT set who have received any amount of study drug and have at least one measurable study drug concentration. Only those participants contributing data at the indicated time point were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (All Arms): Time to Reach Maximum Concentration (Tmax) of Pelabresib

Pharmacokinetic (PK) parameters were calculated based on Pelabresib plasma concentrations and actual sampling time points.

Tmax was listed and summarized using descriptive statistics.

Posted

Median

Full Range

Hour

Cycle 1 Day 14 (predose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (All Arms): Predose (Trough) Concentration at the End of a Dosing Interval (Ctrough) of Pelabresib

Pharmacokinetic (PK) parameters were calculated based on Pelabresib plasma concentrations and actual sampling time points.

Ctrough was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 14 (predose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (All Arms): Area Under the Concentration-Time Curve From Time Zero to the Last Observed Concentration (AUClast) of Pelabresib

Pharmacokinetic (PK) parameters were calculated based on Pelabresib plasma concentrations and actual sampling time points.

AUClast was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (All Arms): Area Under the Concentration-Time Curve From Time Zero to 8 Hours Post-dose at Steady State (AUC0-8,ss) of Pelabresib

Pharmacokinetic (PK) parameters were calculated based on Pelabresib plasma concentrations and actual sampling time points.

AUC0-8,ss was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (All Arms): Time of Last Measurable Concentration (Tlast) of Pelabresib

Pharmacokinetic (PK) parameters were calculated based on Pelabresib plasma concentrations and actual sampling time points.

Tlast was listed and summarized using descriptive statistics.

Posted

Median

Full Range

Hour

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.
OG001	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.

Secondary

Phase 2 (Arm 2 - Cohort 2A): Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Cmax was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2A	In Phase 2 (Arm 2) - Cohort 2A, eligible transfusion-dependent (TD) participants already on ruxolitinib received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), alongside their stable dose of ruxolitinib. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants

Secondary

Phase 2 (Arm 2 - Cohort 2A): Time to Reach Maximum Concentration (Tmax) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Tmax was listed and summarized using descriptive statistics.

Posted

Median

Full Range

Hour

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2A	In Phase 2 (Arm 2) - Cohort 2A, eligible transfusion-dependent (TD) participants already on ruxolitinib received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), alongside their stable dose of ruxolitinib. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants

Secondary

Phase 2 (Arm 2 - Cohort 2A): Predose (Trough) Concentration at the End of a Dosing Interval (Ctrough) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Ctrough was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 14 (predose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2A	In Phase 2 (Arm 2) - Cohort 2A, eligible transfusion-dependent (TD) participants already on ruxolitinib received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), alongside their stable dose of ruxolitinib. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants

Secondary

Phase 2 (Arm 2 - Cohort 2A): Area Under the Concentration-Time Curve From Time Zero to the Last Observed Concentration (AUClast) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

AUClast was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2A	In Phase 2 (Arm 2) - Cohort 2A, eligible transfusion-dependent (TD) participants already on ruxolitinib received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), alongside their stable dose of ruxolitinib. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants

Secondary

Phase 2 (Arm 2 - Cohort 2A): Area Under the Concentration-Time Curve From Time Zero to 8 Hours Post-dose at Steady State (AUC0-8,ss) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

AUC0-8,ss was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2A	In Phase 2 (Arm 2) - Cohort 2A, eligible transfusion-dependent (TD) participants already on ruxolitinib received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), alongside their stable dose of ruxolitinib. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants

Secondary

Phase 2 (Arm 2 - Cohort 2B): Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Cmax was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2B	In Phase 2 (Arm 2) - Cohort 2B, eligible non-transfusion-dependent (non-TD) participants already receiving ruxolitinib were treated with Pelabresib 125 mg once daily for 14 days, followed by a 7-day break (21-day cycle), alongside their stable ruxolitinib dose. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants

Secondary

Phase 2 (Arm 2 - Cohort 2B): Time to Reach Maximum Concentration (Tmax) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Tmax was listed and summarized using descriptive statistics.

Posted

Median

Full Range

Hour

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2B	In Phase 2 (Arm 2) - Cohort 2B, eligible non-transfusion-dependent (non-TD) participants already receiving ruxolitinib were treated with Pelabresib 125 mg once daily for 14 days, followed by a 7-day break (21-day cycle), alongside their stable ruxolitinib dose. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants

Secondary

Phase 2 (Arm 2 - Cohort 2B): Predose (Trough) Concentration at the End of a Dosing Interval (Ctrough) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Ctrough was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2B	In Phase 2 (Arm 2) - Cohort 2B, eligible non-transfusion-dependent (non-TD) participants already receiving ruxolitinib were treated with Pelabresib 125 mg once daily for 14 days, followed by a 7-day break (21-day cycle), alongside their stable ruxolitinib dose. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants

Secondary

Phase 2 (Arm 2 - Cohort 2B): Area Under the Concentration-Time Curve From Time Zero to the Last Observed Concentration (AUClast) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

AUClast was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2B	In Phase 2 (Arm 2) - Cohort 2B, eligible non-transfusion-dependent (non-TD) participants already receiving ruxolitinib were treated with Pelabresib 125 mg once daily for 14 days, followed by a 7-day break (21-day cycle), alongside their stable ruxolitinib dose. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants

Secondary

Phase 2 (Arm 2 - Cohort 2B): Area Under the Concentration-Time Curve From Time Zero to 8 Hours Post-dose at Steady State (AUC0-8,ss) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

AUC0-8,ss was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2B	In Phase 2 (Arm 2) - Cohort 2B, eligible non-transfusion-dependent (non-TD) participants already receiving ruxolitinib were treated with Pelabresib 125 mg once daily for 14 days, followed by a 7-day break (21-day cycle), alongside their stable ruxolitinib dose. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants

Secondary

Phase 2 (Arm 3): Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Cmax was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 3 (Combination Treatment Arm for JAKi-Naïve MF Participants)	Eligible participants in Phase 2 (Arm 3) received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), combined with Ruxolitinib, initiated at one dose level below the recommended amount based on baseline platelet count. Dose escalation: a) Ruxolitinib: Required increase of 5 mg twice daily at Cycle 3 Day 1 if criteria were met, up to 25 mg twice daily; b) Pelabresib: Optional increase from Cycle 5 Day 1 in 25 mg steps, no more than once every two cycles, up to 175 mg once daily. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.

Units	Counts

Secondary

Phase 2 (Arm 3): Time to Reach Maximum Concentration (Tmax) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Tmax was listed and summarized using descriptive statistics.

Posted

Median

Full Range

Hour

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 3 (Combination Treatment Arm for JAKi-Naïve MF Participants)	Eligible participants in Phase 2 (Arm 3) received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), combined with Ruxolitinib, initiated at one dose level below the recommended amount based on baseline platelet count. Dose escalation: a) Ruxolitinib: Required increase of 5 mg twice daily at Cycle 3 Day 1 if criteria were met, up to 25 mg twice daily; b) Pelabresib: Optional increase from Cycle 5 Day 1 in 25 mg steps, no more than once every two cycles, up to 175 mg once daily. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.

Units	Counts
Participants

Secondary

Phase 2 (Arm 3): Predose (Trough) Concentration at the End of a Dosing Interval (Ctrough) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Ctrough was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1 Day 14 (predose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 3 (Combination Treatment Arm for JAKi-Naïve MF Participants)	Eligible participants in Phase 2 (Arm 3) received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), combined with Ruxolitinib, initiated at one dose level below the recommended amount based on baseline platelet count. Dose escalation: a) Ruxolitinib: Required increase of 5 mg twice daily at Cycle 3 Day 1 if criteria were met, up to 25 mg twice daily; b) Pelabresib: Optional increase from Cycle 5 Day 1 in 25 mg steps, no more than once every two cycles, up to 175 mg once daily. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.

Units

Secondary

Phase 2 (Arm 3): Area Under the Concentration-Time Curve From Time Zero to the Last Observed Concentration (AUClast) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

AUClast was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 3 (Combination Treatment Arm for JAKi-Naïve MF Participants)	Eligible participants in Phase 2 (Arm 3) received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), combined with Ruxolitinib, initiated at one dose level below the recommended amount based on baseline platelet count. Dose escalation: a) Ruxolitinib: Required increase of 5 mg twice daily at Cycle 3 Day 1 if criteria were met, up to 25 mg twice daily; b) Pelabresib: Optional increase from Cycle 5 Day 1 in 25 mg steps, no more than once every two cycles, up to 175 mg once daily. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.

Units

Secondary

Phase 2 (Arm 3): Area Under the Concentration-Time Curve From Time Zero to 8 Hours Post-dose at Steady State (AUC0-8,ss) of Ruxolitinib

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

AUC0-8,ss was listed and summarized using descriptive statistics.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

ID	Title	Description
OG000	Phase 2 - Arm 3 (Combination Treatment Arm for JAKi-Naïve MF Participants)	Eligible participants in Phase 2 (Arm 3) received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), combined with Ruxolitinib, initiated at one dose level below the recommended amount based on baseline platelet count. Dose escalation: a) Ruxolitinib: Required increase of 5 mg twice daily at Cycle 3 Day 1 if criteria were met, up to 25 mg twice daily; b) Pelabresib: Optional increase from Cycle 5 Day 1 in 25 mg steps, no more than once every two cycles, up to 175 mg once daily. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1 (24 mg Capsule PO Daily)	Phase 1 (24 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.	0	3	1	3	3	3
EG001	Phase 1 (48 mg Capsule PO Daily)	Phase 1 (48 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.	1	5	4	5	5	5
EG002	Phase 1 (120 mg Capsule PO Daily)	Phase 1 (120 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.	2	5	3	5	5	5
EG003	Phase 1 (170 mg Capsule PO Daily)	Phase 1 (170 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.	0	3	1	3	3	3
EG004	Phase 1 (230 mg Capsule PO Daily)	Phase 1 (230 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.	1	3	2	3	3	3
EG005	Phase 1 (300 mg Capsule PO Daily)	Phase 1 (300 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.	1	4	4	4	4	4
EG006	Phase 1 (400 mg Capsule PO Daily)	Phase 1 (400 mg capsule PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.	1	7	6	7	7	7
EG007	Phase 1 (225 mg Tablet PO Daily)	Phase 1 (225 mg tablet PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.	1	8	6	8	8	8
EG008	Phase 1 (275 mg Tablet PO Daily)	Phase 1 (275 mg tablet PO daily): Eligible participants in Phase I were enrolled in sequential cohorts based on diagnosis and received escalating doses of pelabresib (CPI-0610) once daily for 14 days, followed by a 7-day break in each 21-day cycle. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.	1	6	6	6	6	6
EG009	Phase 1 (Overall)	Phase 1 (Overall): All treated patients in Phase 1	8	44	33	44	44	44
EG010	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1A	In Phase 2 (Arm 1) - Cohort 1A, eligible transfusion-dependent (TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.	6	48	18	48	48	48
EG011	Phase 2 - Arm 1 (MF Participants Previously Treated With JAK Inhibitor Monotherapy) - Cohort 1B	In Phase 2 (Arm 1) - Cohort 1B, eligible non-transfusion-dependent (non-TD) participants received Pelabresib 125 mg QD (tablet) for 14 days, then 7-day break (21-day cycle). Upward titration allowed up to 225 mg QD based on platelet count, hemoglobin, and safety. Treatment stopped upon disease progression, unacceptable toxicity, or pregnancy.	3	52	23	52	50	52
EG012	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2A	In Phase 2 (Arm 2) - Cohort 2A, eligible transfusion-dependent (TD) participants already on ruxolitinib received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), alongside their stable dose of ruxolitinib. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.	3	59	29	59	58	59
EG013	Phase 2 - Arm 2 (Supplement to JAK Inhibitor Combination Arm for MF Participants) - Cohort 2B	In Phase 2 (Arm 2) - Cohort 2B, eligible non-transfusion-dependent (non-TD) participants already receiving ruxolitinib were treated with Pelabresib 125 mg once daily for 14 days, followed by a 7-day break (21-day cycle), alongside their stable ruxolitinib dose. Pelabresib could be titrated up to 225 mg daily. Treatment was discontinued upon disease progression, unacceptable toxicity, or pregnancy.	3	28	18	28	28	28
EG014	Phase 2 - Arm 3 (Combination Treatment Arm for JAKi-Naïve MF Participants)	Eligible participants in Phase 2 (Arm 3) received Pelabresib 125 mg once daily for 14 days followed by a 7-day break (21-day cycle), combined with Ruxolitinib, initiated at one dose level below the recommended amount based on baseline platelet count. Dose escalation: a) Ruxolitinib: Required increase of 5 mg twice daily at Cycle 3 Day 1 if criteria were met, up to 25 mg twice daily; b) Pelabresib: Optional increase from Cycle 5 Day 1 in 25 mg steps, no more than once every two cycles, up to 175 mg once daily. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.	7	84	40	84	84	84
EG015	Phase 2 - Arm 4 (Monotherapy Arm for Essential Thrombocythemia (ET))	Eligible participants in Phase 2 (Arm 4) received Pelabresib 225 mg once daily (tablet) was administered for 14 days followed by a 7-day break (21-day cycle). No dose increases beyond 225 mg once daily were permitted. Treatment was discontinued in cases of disease progression, unacceptable toxicity, or pregnancy.	0	21	5	21	21	21
EG016	Phase 2 (Overall)	Phase 2 (Overall): All treated patients in Phase 2	22	292	133	292	289	292

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG0031 affected3 at risk EG0040 affected3 at risk EG0050 affected4 at risk EG0061 affected7 at risk EG0070 affected8 at risk EG0080 affected6 at risk EG0092 affected44 at risk EG0101 affected48 at risk EG0112 affected52 at risk EG0122 affected59 at risk EG0135 affected28 at risk EG0141 affected84 at risk EG0150 affected21 at risk EG01611 affected292 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0012 affected5 at risk EG0021 affected5 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Leukostasis syndrome	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Splenic infarction	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Splenomegaly	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Acute left ventricular failure	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Cardiac iron overload	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Chronic coronary syndrome	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Dilated cardiomyopathy	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Left ventricular dysfunction	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Left ventricular failure	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pericarditis	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Right ventricular failure	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Adrenal haematoma	Endocrine disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Abdominal wall haematoma	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Intestinal haematoma	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Asthenia	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Chest pain	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Chills	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Disease progression	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Drug withdrawal syndrome	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Fatigue	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected5 at risk EG0020 affected5 at risk EG003
Malaise	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Multiple organ dysfunction syndrome	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Oedema	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pyrexia	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Biliary dilatation	Hepatobiliary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hepatocellular injury	Hepatobiliary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Serum sickness	Immune system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Abscess limb	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Aspergillus infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Bacteraemia	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Bronchiolitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Bronchopulmonary aspergillosis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
COVID-19	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Cellulitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Dermo-hypodermitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Device related infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Device related sepsis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Diverticulitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Empyema	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Endocarditis bacterial	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Enterococcal bacteraemia	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Escherichia bacteraemia	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Escherichia infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Escherichia urinary tract infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Fournier's gangrene	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Herpes simplex reactivation	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Herpes zoster	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Influenza	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Localised infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Nocardiosis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pneumonia	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected5 at risk EG003
Pneumonia acinetobacter	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pneumonia bacterial	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pneumonia pneumococcal	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pneumonia staphylococcal	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Post procedural infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pyelonephritis acute	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Sepsis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Septic shock	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Streptococcal sepsis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Tooth infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Urosepsis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Viral infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Extradural haematoma	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Blast cell count increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Blood creatinine increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Ejection fraction decreased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Platelet count decreased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Failure to thrive	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected5 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Bowen's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Colon cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Glioblastoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Haematopoietic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Invasive breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Keratoacanthoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Metastatic squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Neuroendocrine carcinoma of the skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Oropharyngeal squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Ovarian neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Squamous cell carcinoma of head and neck	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Transformation to acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Brain stem haemorrhage	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Cerebral infarction	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Haemorrhage intracranial	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Metabolic encephalopathy	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Spinal cord compression	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Subarachnoid haemorrhage	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Superior sagittal sinus thrombosis	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Syncope	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Confusional state	Psychiatric disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Delirium	Psychiatric disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Depression	Psychiatric disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Renal cyst ruptured	Renal and urinary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Renal haemorrhage	Renal and urinary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Organising pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Cutaneous vasculitis	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Aortic dissection	Vascular disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Haematoma	Vascular disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hypertension	Vascular disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hypotension	Vascular disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Peripheral ischaemia	Vascular disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected5 at risk EG0021 affected5 at risk EG0030 affected3 at risk EG0041 affected3 at risk EG0051 affected4 at risk EG0064 affected7 at risk EG0071 affected8 at risk EG0082 affected6 at risk EG00912 affected44 at risk EG01017 affected48 at risk EG01115 affected52 at risk EG01218 affected59 at risk EG0137 affected28 at risk EG01441 affected84 at risk EG0151 affected21 at risk EG01699 affected292 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Spleen disorder	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Thrombocytosis	Blood and lymphatic system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Atrioventricular block	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hyperdynamic left ventricle	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Palpitations	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Tachycardia	Cardiac disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Ear discomfort	Ear and labyrinth disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Ear haemorrhage	Ear and labyrinth disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Eye haemorrhage	Eye disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Vision blurred	Eye disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Anal incontinence	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Eructation	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected5 at risk EG0020 affected5 at risk EG003
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Mouth haemorrhage	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0002 affected3 at risk EG0013 affected5 at risk EG0024 affected5 at risk EG003
Oral disorder	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected5 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected5 at risk EG0021 affected5 at risk EG003
Asthenia	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0022 affected5 at risk EG003
Chest pain	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Chills	General disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Early satiety	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Fatigue	General disorders	MedDRA (26.0)	Systematic Assessment	EG0002 affected3 at risk EG0013 affected5 at risk EG0024 affected5 at risk EG003
Gait disturbance	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Influenza like illness	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Malaise	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Mucosal inflammation	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Nodule	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Oedema peripheral	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0013 affected5 at risk EG0020 affected5 at risk EG003
Pain	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Peripheral swelling	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pyrexia	General disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Bronchitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
COVID-19	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Cellulitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Cystitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Eye infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Folliculitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Fungal skin infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Herpes simplex reactivation	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Herpes zoster	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hordeolum	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Influenza	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Localised infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Oral herpes	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Orchitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Otitis media	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pharyngitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pneumonia	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected5 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Rhinitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Septic shock	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Sinusitis	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Skin infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Staphylococcal infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Tooth infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Urinary tract infection bacterial	Infections and infestations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Nail injury	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Procedural site reaction	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Vascular access site complication	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Wound	Injury, poisoning and procedural complications	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Activated partial thromboplastin time prolonged	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Bilirubin conjugated increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Blast cell count increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Blood creatinine increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected5 at risk EG003
Blood phosphorus increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Blood uric acid increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Cardiac murmur	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Ejection fraction decreased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Electrocardiogram QRS complex abnormal	Investigations	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Haematocrit increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
International normalised ratio increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Platelet count decreased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0002 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Transaminases increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Troponin T increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Weight decreased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Weight increased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
White blood cell count decreased	Investigations	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0023 affected5 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Folate deficiency	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hypermagnesaemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected5 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Iron overload	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Tumour lysis syndrome	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Bone cyst	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Gouty arthritis	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected5 at risk EG0020 affected5 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Musculoskeletal disorder	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Ageusia	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Dizziness	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Dysarthria	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected5 at risk EG003
Headache	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0012 affected5 at risk EG0022 affected5 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Lethargy	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Memory impairment	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Migraine	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Myoclonus	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Presyncope	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Sciatica	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Syncope	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Taste disorder	Nervous system disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (26.0)	Systematic Assessment	EG0002 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Confusional state	Psychiatric disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Delirium	Psychiatric disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Depression	Psychiatric disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Micturition urgency	Renal and urinary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Genital lesion	Reproductive system and breast disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0002 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0021 affected5 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Sinus pain	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Petechiae	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0020 affected5 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Skin induration	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Flushing	Vascular disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Haematoma	Vascular disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hot flush	Vascular disorders	MedDRA (26.0)	Systematic Assessment	EG0001 affected3 at risk EG0010 affected5 at risk EG0020 affected5 at risk EG003
Hypertension	Vascular disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected5 at risk EG003
Hypotension	Vascular disorders	MedDRA (26.0)	Systematic Assessment	EG0000 affected3 at risk EG0011 affected5 at risk EG0021 affected5 at risk EG003

ID	Term
D055728	Primary Myelofibrosis
D015470	Leukemia, Myeloid, Acute
D054437	Myelodysplastic-Myeloproliferative Diseases
D009190	Myelodysplastic Syndromes
D011289	Preleukemia
D009196	Myeloproliferative Disorders
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D011230	Precancerous Conditions
D009369	Neoplasms
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D013920	Thrombocythemia, Essential

ID	Term
D006425	Hemic and Lymphatic Diseases
D007951	Leukemia, Myeloid
D001778	Blood Coagulation Disorders
D013922	Thrombocytosis
D001791	Blood Platelet Disorders
D006474	Hemorrhagic Disorders