To Evaluate Efficacy and Safety of Parsaclisib and Ruxoli... | NCT04551053

NCT04551053

ID	Type	Description	Link
2020-003415-98	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group A : ruxolitinib +parsaclisib	Experimental	Participants will receive parsaclisib starting from Day 1 for the duration of study, while continuing to receive the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1.	Drug: parsaclisib Drug: ruxolitinib
Group B : ruxolitinib + placebo	Placebo Comparator	Participants will receive placebo starting from Day 1 for the duration of study, while continuing to receive the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1.	Drug: ruxolitinib Drug: placebo

Name	Type	Description	Arm Group Labels	Other Names
parsaclisib	Drug	parsaclisib will be administered QD orally	Group A : ruxolitinib +parsaclisib

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants Achieving ≥25% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging (MRI) (or Computed Tomography [CT] Scan in Applicable Participants)	Participants had an MRI of the upper and lower abdomen and pelvis to determine the spleen volume. A CT scan was substituted for participants who were not candidates for MRI or when MRI was not readily available.	Baseline; Week 24

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Have a ≥50% Reduction in Total Symptom Score (TSS) From Baseline to Week 24 as Measured by the Myelofibrosis Symptom Assessment Form v.4.0 (MFSAF v4.0) Diary	Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected in a day. A higher TSS corresponds to more severe symptoms. The TSS was marked as missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total score was marked as missing if there were ≥4 out of the 7 daily TSSs missing.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis of PMF, PPV-MF, or PET-MF.
DIPSS risk category of intermediate-1, intermediate-2, or high.
Treated with ruxolitinib for ≥ 3 months with a stable dose for at least the last 8 weeks prior to Day 1
Palpable spleen of ≥ 5 cm below the left costal margin on physical examination at the screening visit.
Active symptoms of MF at the screening visit, as demonstrated by the presence of a TSS of ≥ 10 using the Screening Symptom Form.
Participants with an ECOG performance status score of 0, 1, or 2.
Screening bone marrow biopsy specimen and pathology report(s) available that was obtained within the prior 2 months or willingness to undergo a bone marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at Week 24 and every 24 weeks there after. Screening/baseline biopsy specimen must show diagnosis of MF.
Life expectancy of at least 24 weeks.
Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

Prior therapy with any drug that inhibits PI3K (examples of drugs targeting this pathway include but are not limited to INCB040093, idelalisib, duvelisib, buparlisib, copanlisib, and umbralisib).
Use of experimental drug therapy for MF or any other standard drug used for MF (whether for treatment of MF or another indication) with the exception of ruxolitinib, within 3 months of starting study drug, and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better.
Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
Recent history of inadequate bone marrow reserve.
Inadequate liver and renal function at screening.
Active bacterial, fungal, parasitic, or viral infection that requires therapy.
Active HBV or HCV infection that requires treatment or at risk for HBV reactivation.
Known HIV infection.
Uncontrolled, severe, or unstable cardiac disease that in the investigator's opinion may jeopardize the safety of the participant or compliance with the Protocol.
Active invasive malignancy over the previous 2 years.
Splenic irradiation within 6 months before receiving the first dose of study drug.
Concurrent use of any prohibited medications.
Active alcohol or drug addiction that would interfere with the ability to comply with the study requirements.
Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives(whichever is longer) before the first dose of study drug or anticipated during the study.
Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
Currently breastfeeding or pregnant.
Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
History of Grade 3 or 4 irAEs from prior immunotherapy.
Receipt of any live vaccine within 30 days of the first dose of study drug
Unwillingness to receive RBC transfusions to treat low hemoglobin levels.
Known hypersensitivity or severe reaction to parsaclisib or ruxolitinib or excipients of parsaclisib/matching placebo or ruxolitinib formulations.

Name	Affiliation	Role
Albert Assad, M.D.	Incyte Corporation	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Sutter Health Alta Bates Summit Medical Center Absmc Alta Bates Summit Comprehensive Cancer Center		Berkeley	California	94704	United States

Label	URL
Related Info	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Parsaclisib Plus Ruxolitinib	Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1. Participants received parsaclisib at a dose of 5 milligrams (mg) once daily (QD). Participants also received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. Treatment with parsaclisib plus ruxolitinib continued for as long as the participant tolerated the regimen and did not meet any discontinuation criteria.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 20, 2022	Jul 15, 2024

Arm/Group Information

ID	Title	Description
BG000	Parsaclisib Plus Ruxolitinib	Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1. Participants received parsaclisib at a dose of 5 milligrams (mg) once daily (QD). Participants also received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. Treatment with parsaclisib plus ruxolitinib continued for as long as the participant tolerated the regimen and did not meet any discontinuation criteria.
BG001	Placebo Plus Ruxolitinib	Participants were randomized to receive placebo plus ruxolitinib beginning on Day 1 and continuing until Week 24. Participants received matching placebo at a dose of 5 mg QD and received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. After 24 weeks, participants randomized to receive placebo plus ruxolitinib had to switch to treatment with parsaclisib plus ruxolitinib or discontinue treatment. Treatment continued for as long as the regimen was tolerated and the participant did not meet any discontinuation criteria. Participants who demonstrated worsening symptomatic splenomegaly could have switched to treatment with parsaclisib plus ruxolitinib early.
BG002	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

Percentage of Participants Achieving ≥25% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging (MRI) (or Computed Tomography [CT] Scan in Applicable Participants)

Participants had an MRI of the upper and lower abdomen and pelvis to determine the spleen volume. A CT scan was substituted for participants who were not candidates for MRI or when MRI was not readily available.

Intent-to-Treat (ITT) Population: all randomized participants. Participants were analyzed if they had both Baseline and Week 24 measurements, or discontinued treatment before 03MAR2023 or switched treatment before Week 24, or reached Week 24 before 03MAR2023 but were missing Week 24 assessments. For participants who switched to parsaclisib plus ruxolitinib treatment early, data was truncated at the time of switch.

Posted

Number

percentage of participants

Baseline; Week 24

ID	Title	Description
OG000	Parsaclisib Plus Ruxolitinib	Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1. Participants received parsaclisib at a dose of 5 milligrams (mg) once daily (QD). Participants also received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. Treatment with parsaclisib plus ruxolitinib continued for as long as the participant tolerated the regimen and did not meet any discontinuation criteria.
OG001	Placebo Plus Ruxolitinib	Participants were randomized to receive placebo plus ruxolitinib beginning on Day 1 and continuing until Week 24. Participants received matching placebo at a dose of 5 mg QD and received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. After 24 weeks, participants randomized to receive placebo plus ruxolitinib had to switch to treatment with parsaclisib plus ruxolitinib or discontinue treatment. Treatment continued for as long as the regimen was tolerated and the participant did not meet any discontinuation criteria. Participants who demonstrated worsening symptomatic splenomegaly could have switched to treatment with parsaclisib plus ruxolitinib early.

Units	Counts
Participants	OG00072 OG00172

Title

Denominators

Categories

Title	Measurements
	OG00016.7 OG0019.7

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cochran-Mantel-Haenszel		0.2567	CMH test for un-equality stratified by Dynamic International Prognostic Scoring System (DIPSS) category (intermediate 1 versus intermediate 2 and high) and Baseline platelet count (≥100 × 10^9/Liters [L] versus 50 to <100 × 10^9/L inclusive)	Odds Ratio (OR)	1.80			2-Sided	95	0.65	5.02					Superiority	p-value for superiority is half of the CMH p-value.

Secondary

Percentage of Participants Who Have a ≥50% Reduction in Total Symptom Score (TSS) From Baseline to Week 24 as Measured by the Myelofibrosis Symptom Assessment Form v.4.0 (MFSAF v4.0) Diary

Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected in a day. A higher TSS corresponds to more severe symptoms. The TSS was marked as missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total score was marked as missing if there were ≥4 out of the 7 daily TSSs missing.

ITT Population. Participants were analyzed if they had both Baseline and Week 24 measurements, or discontinued treatment before 03MAR2023 or switched treatment before Week 24, or reached Week 24 before 03MAR2023 but were missing Week 24 assessments. For participants who switched to parsaclisib plus ruxolitinib treatment early, data was truncated at the time of switch.

Posted

Number

percentage of participants

Baseline; Week 24

ID	Title	Description
OG000	Parsaclisib Plus Ruxolitinib	Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1. Participants received parsaclisib at a dose of 5 milligrams (mg) once daily (QD). Participants also received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. Treatment with parsaclisib plus ruxolitinib continued for as long as the participant tolerated the regimen and did not meet any discontinuation criteria.

Secondary

Change in TSS From Baseline to Week 24 as Measured by the MFSAF v4.0 Diary

ITT Population. Only participants with data available were analyzed.

Posted

Mean

Standard Deviation

scores on a scale

Baseline; Week 24

ID	Title	Description
OG000	Parsaclisib Plus Ruxolitinib	Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1. Participants received parsaclisib at a dose of 5 milligrams (mg) once daily (QD). Participants also received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. Treatment with parsaclisib plus ruxolitinib continued for as long as the participant tolerated the regimen and did not meet any discontinuation criteria.

Secondary

Time to the First ≥50% Reduction in TSS as Measured by the MFSAF v4.0 Diary

Symptoms were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected in a day. A higher TSS corresponds to more severe symptoms. The TSS was marked as missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total scores was marked as missing if there were ≥4 out of the 7 daily TSSs missing. The 95% confidence interval was calculated using the Brookmeyer and Crowley's method with log-log transformation.

ITT Population. For participants who switched to parsaclisib plus ruxolitinib treatment early, data was truncated at the time of switch. Participants with valid, calculated Baseline TSS and at least 1 postbaseline TSS who did not have a ≥50% reduction in TSS at the time of analysis were censored at the time of the last valid calculated TSS. If the participants had no valid, calculated Baseline or postbaseline TSS, they were censored at the date of randomization.

Posted

Median

95% Confidence Interval

days

Baseline; up to Week 24

ID	Title	Description
OG000	Parsaclisib Plus Ruxolitinib	Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1. Participants received parsaclisib at a dose of 5 milligrams (mg) once daily (QD). Participants also received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. Treatment with parsaclisib plus ruxolitinib continued for as long as the participant tolerated the regimen and did not meet any discontinuation criteria.

Secondary

Overall Survival

Overall survival was defined as the interval between the randomization date and the date of death due to any cause.

ITT Population

Posted

Median

95% Confidence Interval

days

up to 917 days

ID	Title	Description
OG000	Parsaclisib Plus Ruxolitinib	Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1. Participants received parsaclisib at a dose of 5 milligrams (mg) once daily (QD). Participants also received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. Treatment with parsaclisib plus ruxolitinib continued for as long as the participant tolerated the regimen and did not meet any discontinuation criteria.
OG001	Placebo Plus Ruxolitinib	Participants were randomized to receive placebo plus ruxolitinib beginning on Day 1 and continuing until Week 24. Participants received matching placebo at a dose of 5 mg QD and received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. After 24 weeks, participants randomized to receive placebo plus ruxolitinib had to switch to treatment with parsaclisib plus ruxolitinib or discontinue treatment. Treatment continued for as long as the regimen was tolerated and the participant did not meet any discontinuation criteria. Participants who demonstrated worsening symptomatic splenomegaly could have switched to treatment with parsaclisib plus ruxolitinib early.

Secondary

Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE is defined as an AE reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.

Safety Population: all randomized participants who received at least 1 dose of parsaclisib, placebo, or ruxolitinib. Treatment groups for this population were determined according to the actual treatment the participant received regardless of assigned study drug treatment.

Posted

Count of Participants

Participants

up to 917 days

ID	Title	Description
OG000	Parsaclisib Plus Ruxolitinib	Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1. Participants received parsaclisib at a dose of 5 milligrams (mg) once daily (QD). Participants also received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. Treatment with parsaclisib plus ruxolitinib continued for as long as the participant tolerated the regimen and did not meet any discontinuation criteria.
OG001	Placebo Plus Ruxolitinib	Participants were randomized to receive placebo plus ruxolitinib beginning on Day 1 and continuing until Week 24. Participants received matching placebo at a dose of 5 mg QD and received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. After 24 weeks, participants randomized to receive placebo plus ruxolitinib had to switch to treatment with parsaclisib plus ruxolitinib or discontinue treatment. Treatment continued for as long as the regimen was tolerated and the participant did not meet any discontinuation criteria. Participants who demonstrated worsening symptomatic splenomegaly could have switched to treatment with parsaclisib plus ruxolitinib early.

Secondary

Number of Participants With Any Grade 3 or Higher TEAE

An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. A TEAE is defined as an AE reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local or noninvasive intervention indicated; limiting instrumental activities of daily living (ADL). Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: life-threatening urgent intervention indicated. Grade 5: death related to AE.

Safety Population

Posted

Count of Participants

Participants

up to 917 days

ID	Title	Description
OG000	Parsaclisib Plus Ruxolitinib	Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1. Participants received parsaclisib at a dose of 5 milligrams (mg) once daily (QD). Participants also received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. Treatment with parsaclisib plus ruxolitinib continued for as long as the participant tolerated the regimen and did not meet any discontinuation criteria.
OG001	Placebo Plus Ruxolitinib

Secondary

Time to the First ≥25% Reduction in Spleen Volume

The time to the first ≥25% reduction in spleen volume is defined as the time from randomization to the first time participants had ≥25% reduction in spleen volume. Participants with a Baseline and post-Baseline MRI or CT scan who did not have ≥25% reduction in spleen volume at the time of analysis were censored at the time of the last MRI or CT scan. If the participants had no Baseline or post-Baseline MRI or CT scan, they were censored at the date of randomization.

ITT Population

Posted

Median

95% Confidence Interval

days

up to 898 days

ID	Title	Description
OG000	Parsaclisib Plus Ruxolitinib	Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1. Participants received parsaclisib at a dose of 5 milligrams (mg) once daily (QD). Participants also received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. Treatment with parsaclisib plus ruxolitinib continued for as long as the participant tolerated the regimen and did not meet any discontinuation criteria.
OG001	Placebo Plus Ruxolitinib	Participants were randomized to receive placebo plus ruxolitinib beginning on Day 1 and continuing until Week 24. Participants received matching placebo at a dose of 5 mg QD and received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. After 24 weeks, participants randomized to receive placebo plus ruxolitinib had to switch to treatment with parsaclisib plus ruxolitinib or discontinue treatment. Treatment continued for as long as the regimen was tolerated and the participant did not meet any discontinuation criteria. Participants who demonstrated worsening symptomatic splenomegaly could have switched to treatment with parsaclisib plus ruxolitinib early.

Secondary

Duration of Maintenance of a ≥25% Reduction in Spleen Volume

The duration of ≥25% reduction from Baseline in spleen volume was defined as the interval between the first spleen volume measurement that was a ≥25% reduction from Baseline and the date of the first measurement that was no longer a ≥25% reduction from Baseline. If the end date was not observed before the database cutoff, the duration was censored at the last assessment.

ITT Population. Only those participants who had at least 1 measurement of ≥25% reduction from Baseline were to be analyzed. At the time of study termination, only a limited number of ≥25% reduction in spleen volume responses were observed; therefore, as specified in the Statistical Analysis Plan, analysis of duration of a 25% reduction in spleen volume was not performed.

Posted

up to 898 days

ID	Title	Description
OG000	Parsaclisib Plus Ruxolitinib	Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1. Participants received parsaclisib at a dose of 5 milligrams (mg) once daily (QD). Participants also received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. Treatment with parsaclisib plus ruxolitinib continued for as long as the participant tolerated the regimen and did not meet any discontinuation criteria.
OG001	Placebo Plus Ruxolitinib	Participants were randomized to receive placebo plus ruxolitinib beginning on Day 1 and continuing until Week 24. Participants received matching placebo at a dose of 5 mg QD and received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. After 24 weeks, participants randomized to receive placebo plus ruxolitinib had to switch to treatment with parsaclisib plus ruxolitinib or discontinue treatment. Treatment continued for as long as the regimen was tolerated and the participant did not meet any discontinuation criteria. Participants who demonstrated worsening symptomatic splenomegaly could have switched to treatment with parsaclisib plus ruxolitinib early.

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	Parsaclisib Plus Ruxolitinib	Participants were randomized to receive parsaclisib plus ruxolitinib beginning on Day 1. Participants received parsaclisib at a dose of 5 milligrams (mg) once daily (QD). Participants also received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. Treatment with parsaclisib plus ruxolitinib continued for as long as the participant tolerated the regimen and did not meet any discontinuation criteria.	10	90	33	90	71	90
EG001	Placebo Plus Ruxolitinib	Participants were randomized to receive placebo plus ruxolitinib beginning on Day 1 and continuing until Week 24. Participants received matching placebo at a dose of 5 mg QD and received the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1. After 24 weeks, participants randomized to receive placebo plus ruxolitinib had to switch to treatment with parsaclisib plus ruxolitinib or discontinue treatment. Treatment continued for as long as the regimen was tolerated and the participant did not meet any discontinuation criteria. Participants who demonstrated worsening symptomatic splenomegaly could have switched to treatment with parsaclisib plus ruxolitinib early.	7	87	15	87	58	87
EG002	Placebo Swith to Parsaclisib	After 24 weeks, participants randomized to receive placebo plus ruxolitinib from Day 1 to Week 24 could have switched to treatment with parsaclisib plus ruxolitinib per the regimen received during the first 24 weeks of the study. Treatment continued for as long as the regimen was tolerated and the participant did not meet any discontinuation criteria. Participants who demonstrated worsening symptomatic splenomegaly could have switched to treatment with parsaclisb plus ruxolitinib early.	2	41	8	41	25	41

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abscess	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected90 at risk EG0012 events2 affected87 at risk EG0020 events0 affected41 at risk
Anal abscess	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Arterial injury	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0021 events1 affected41 at risk
Breast neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Bronchitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Bronchopulmonary aspergillosis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0010 events0 affected87 at risk EG0021 events1 affected41 at risk
COVID-19	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0003 events3 affected90 at risk EG0010 events0 affected87 at risk EG0021 events1 affected41 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0005 events5 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Chest pain	General disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Diarrhoea infectious	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0010 events0 affected87 at risk EG0021 events1 affected41 at risk
Dizziness	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Enterocolitis bacterial	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0010 events0 affected87 at risk EG0021 events1 affected41 at risk
Enterocolitis infectious	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Faeces discoloured	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Gastroenteritis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0010 events0 affected87 at risk EG0021 events1 affected41 at risk
Herpes zoster	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Influenza	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0010 events0 affected87 at risk EG0021 events1 affected41 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Malaise	General disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Necrotising colitis	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0010 events0 affected87 at risk EG0021 events1 affected41 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Papillary renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Platelet count decreased	Investigations	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected90 at risk EG0010 events0 affected87 at risk EG0021 events1 affected41 at risk
Pneumonia	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG00011 events8 affected90 at risk EG0012 events2 affected87 at risk EG0022 events2 affected41 at risk
Pneumonia cytomegaloviral	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Pneumonia escherichia	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Pneumonia influenzal	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0010 events0 affected87 at risk EG0021 events1 affected41 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Pyoderma gangrenosum	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0010 events0 affected87 at risk EG0021 events1 affected41 at risk
Pyrexia	General disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Skin squamous cell carcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Splenic haemorrhage	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Subcapsular splenic haematoma	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0021 events1 affected41 at risk
Syncope	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk
Transformation to acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Ulcerative gastritis	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0010 events0 affected87 at risk EG0021 events1 affected41 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0011 events1 affected87 at risk EG0020 events0 affected41 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0009 events8 affected90 at risk EG0012 events2 affected87 at risk EG0020 events0 affected41 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0009 events8 affected90 at risk EG0014 events3 affected87 at risk EG0024 events4 affected41 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG00038 events26 affected90 at risk EG00136 events20 affected87 at risk EG0026 events6 affected41 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0004 events4 affected90 at risk EG0013 events3 affected87 at risk EG0023 events3 affected41 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0008 events7 affected90 at risk EG0015 events4 affected87 at risk EG0025 events4 affected41 at risk
Asthenia	General disorders	MedDRA 27.1	Systematic Assessment	EG0007 events7 affected90 at risk EG0014 events4 affected87 at risk EG0023 events3 affected41 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0004 events4 affected90 at risk EG0015 events5 affected87 at risk EG0020 events0 affected41 at risk
COVID-19	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG00016 events16 affected90 at risk EG00110 events10 affected87 at risk EG0026 events6 affected41 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0007 events6 affected90 at risk EG0010 events0 affected87 at risk EG0020 events0 affected41 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0008 events8 affected90 at risk EG0014 events4 affected87 at risk EG0022 events2 affected41 at risk
Cytomegalovirus infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG00010 events10 affected90 at risk EG0010 events0 affected87 at risk EG0022 events2 affected41 at risk
Cytomegalovirus test positive	Investigations	MedDRA 27.1	Systematic Assessment	EG0004 events4 affected90 at risk EG0010 events0 affected87 at risk EG0023 events3 affected41 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00010 events10 affected90 at risk EG00110 events9 affected87 at risk EG0024 events1 affected41 at risk
Dizziness	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0009 events7 affected90 at risk EG0012 events2 affected87 at risk EG0021 events1 affected41 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0006 events6 affected90 at risk EG0013 events3 affected87 at risk EG0020 events0 affected41 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0006 events5 affected90 at risk EG0015 events3 affected87 at risk EG0020 events0 affected41 at risk
Fatigue	General disorders	MedDRA 27.1	Systematic Assessment	EG0006 events5 affected90 at risk EG0014 events4 affected87 at risk EG0020 events0 affected41 at risk
Headache	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0008 events8 affected90 at risk EG0014 events4 affected87 at risk EG0021 events1 affected41 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0007 events7 affected90 at risk EG0014 events4 affected87 at risk EG0020 events0 affected41 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0008 events7 affected90 at risk EG0018 events7 affected87 at risk EG0022 events2 affected41 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected90 at risk EG0013 events1 affected87 at risk EG0023 events3 affected41 at risk
Neutrophil count decreased	Investigations	MedDRA 27.1	Systematic Assessment	EG0007 events5 affected90 at risk EG0013 events3 affected87 at risk EG0021 events1 affected41 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0005 events5 affected90 at risk EG0013 events3 affected87 at risk EG0021 events1 affected41 at risk
Platelet count decreased	Investigations	MedDRA 27.1	Systematic Assessment	EG00033 events20 affected90 at risk EG00123 events14 affected87 at risk EG0025 events5 affected41 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0005 events5 affected90 at risk EG00110 events6 affected87 at risk EG0020 events0 affected41 at risk
Pyrexia	General disorders	MedDRA 27.1	Systematic Assessment	EG00020 events13 affected90 at risk EG00114 events8 affected87 at risk EG0022 events1 affected41 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0008 events6 affected90 at risk EG0012 events2 affected87 at risk EG0021 events1 affected41 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG00011 events10 affected90 at risk EG00110 events8 affected87 at risk EG00214 events8 affected41 at risk
White blood cell count decreased	Investigations	MedDRA 27.1	Systematic Assessment	EG00012 events8 affected90 at risk EG00117 events7 affected87 at risk EG0020 events0 affected41 at risk

ID	Term
D055728	Primary Myelofibrosis
D009196	Myeloproliferative Disorders

ID	Term
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases