A Phase 1/2 Study to Evaluate Axatilimab in Participants... | NCT03604692

Label	Type	Description	Intervention Names
Cohorts of escalating dose levels of axatilimab	Experimental	Escalating dose levels of axatilimab to establish the optimal biologic dose (OBD) and recommended Phase 2 dose (RP2D). Intravenous (IV) infusion; axatilimab at a dose of 0.15 milligrams (mg)/kilogram (kg) to 3 mg/kg.	Drug: axatilimab
Phase 2 Dose Expansion	Experimental	Phase 2, dose expansion, is an open-label design, evaluating the 1 mg/kg dose in a larger sample size. IV infusion; axatilimab at a dose of 1 mg/kg.	Drug: axatilimab

Name	Type	Description	Arm Group Labels	Other Names
axatilimab	Drug	axatilimab is a high affinity antibody targeting the colony stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be the key regulatory pathway involved in the expansion and infiltration of donor derived macrophages that mediate the disease processes involved in cGVHD.

Measure	Description	Time Frame
Phase 1: Number of Participants With DLTs	A DLT was defined as the occurrence of any protocol-specified event within the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1) and assessed by the Investigator as not being definitely attributable to underlying disease, disease progression, inter-current illness, concomitant medications or any other alternative cause.	Day 1 through the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1)
Phase 1: Recommended Phase 2 Dose (RP2D)	The RP2D was determined in discussion with the Sponsor, Medical Monitor, and Dose Determination Phase Investigators and was based on observations from the Phase 1 of the study (clinical benefit in chronic graft versus host disease [cGVHD] and pharmacokinetic/pharmacodynamic effects).	Day 1 through the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from C1D1 to C2D1)
Phase 2: Overall Response Rate (ORR) as Assessed by the Number of Participants With Complete Response (CR) or Partial Response (PR) at Cycle 7 Day 1 (Day 168)	CR or PR was defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in cGVHD.CR was defined as resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. ORR was defined as the percentage of participants achieving a best overall response of CR or PR .ORR calculated as: (number of participants with best overall response as CR or PR)/total number of participants.	Cycle 7 Day 1 (Day 168)

Measure	Description	Time Frame
Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352	Blood samples were collected for determination of SNDX-6352 concentration.	Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15
Phase 1: Observed Maximum Plasma Concentration for SNDX-6352

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Participant must be 6 years of age or older, at the time of signing the informed consent.
Participants who are allogeneic hematopoietic stem cell transplant (HSCT) recipients with cGVHD requiring systemic immune suppression.
Participants with active cGVHD who have received at least 2 lines of therapy. Participants 18 or older with active cGVHD who have erythematous rash involving >25% body surface area or a NIH mouth score of >4 must have received prior ibrutinib therapy.

a. Active cGVHD is defined as the presence of signs and symptoms of cGVHD per 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.
Participants may have persistent active acute and cGVHD manifestations (overlap syndrome), as defined by 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.
Karnofsky Performance Scale of ≥60 with a life expectancy of at least 3 months (if aged 16 years or older); Lansky Performance Score of ≥60 (if less than 16 years).
Adequate organ and bone marrow functions.
Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Capable of giving signed informed consent which includes compliance with the study requirements and restrictions.

Key Exclusion Criteria:

Has acute GVHD without manifestations of cGVHD.
Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
History or other evidence of severe illness, uncontrolled infection or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study.
Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV).
Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of enrollment, unless previously treated with curative intent and must be approved by Sponsor medical monitor (for example, completely resected basal cell or squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection).
Female participants who are pregnant or breastfeeding.
Previous exposure to study intervention or known allergy/sensitivity to study intervention.
Taking agents other than a corticosteroid and one calcineurin inhibitor (CNI) for treatment of cGVHD (This does not include agents being prescribed expressly for the treatment of acute GVHD).
Receiving an investigational treatment within 28 days of study entry.

Name	Affiliation	Role
Vedran Radojcic, M.D.	Syndax Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35294	United States
City of Hope

PubMed Identifier	Type	Citation	Retractions
36459673	Derived	Kitko CL, Arora M, DeFilipp Z, Zaid MA, Di Stasi A, Radojcic V, Betts CB, Coussens LM, Meyers ML, Qamoos H, Ordentlich P, Kumar V, Quaranto C, Schmitt A, Gu Y, Blazar BR, Wang TP, Salhotra A, Pusic I, Jagasia M, Lee SJ. Axatilimab for Chronic Graft-Versus-Host Disease After Failure of at Least Two Prior Systemic Therapies: Results of a Phase I/II Study. J Clin Oncol. 2023 Apr 1;41(10):1864-1875. doi: 10.1200/JCO.22.00958. Epub 2022 Dec 2.

ID	Title	Description
FG000	Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg Q2W	Participants received an intravenous (IV) infusion of SNDX-6352 0.15 milligrams (mg)/kilogram (kg) every 2 weeks (Q2W).
FG001	Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg Q2W

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 12, 2022	Aug 11, 2023

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: Number of Participants With DLTs

A DLT was defined as the occurrence of any protocol-specified event within the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1) and assessed by the Investigator as not being definitely attributable to underlying disease, disease progression, inter-current illness, concomitant medications or any other alternative cause.

Participants who received at least 1 cycle of treatment and had at least one post-baseline response assessment.

Posted

Count of Participants

Participants

Day 1 through the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1)

ID	Title	Description
OG000	Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg	Participants received an IV infusion of SNDX-6352 0.15 mg/kg Q2W.
OG001	Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg	Participants received an IV infusion of SNDX-6352 0.5 mg/kg Q2W.
OG002	Phase 1 Dose Escalation: SNDX-6352 1 mg/kg	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.
OG003	Phase 1 Dose Escalation: SNDX-6352 3 mg/kg	Participants received an IV infusion of SNDX-6352 3 mg/kg Q2W.
OG004	Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W	Participants received an IV infusion of SNDX-6352 3 mg/kg Q4W.

Units	Counts
Participants	OG0001 OG0011 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Primary

Phase 1: Recommended Phase 2 Dose (RP2D)

The RP2D was determined in discussion with the Sponsor, Medical Monitor, and Dose Determination Phase Investigators and was based on observations from the Phase 1 of the study (clinical benefit in chronic graft versus host disease [cGVHD] and pharmacokinetic/pharmacodynamic effects).

Participants who received at least 1 cycle of treatment and had at least one post-baseline response assessment in Phase 1.

Posted

Number

mg/kg

Day 1 through the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from C1D1 to C2D1)

ID	Title	Description
OG000	Phase 1 Dose Determination:SNDX-6352	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.

Units	Counts
Participants	OG000

Primary

Phase 2: Overall Response Rate (ORR) as Assessed by the Number of Participants With Complete Response (CR) or Partial Response (PR) at Cycle 7 Day 1 (Day 168)

CR or PR was defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in cGVHD.CR was defined as resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. ORR was defined as the percentage of participants achieving a best overall response of CR or PR .ORR calculated as: (number of participants with best overall response as CR or PR)/total number of participants.

Safety Analysis Set: All participants who received at least 1 dose of study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

Cycle 7 Day 1 (Day 168)

ID	Title	Description
OG000	Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.

Units	Counts
Participants	OG000

Secondary

Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352

Blood samples were collected for determination of SNDX-6352 concentration.

Pharmacokinetic Analysis Set: All treated participants who had at least 1 plasma concentration measured. Number Analyzed = participants who were evaluable at specified timepoints

Posted

Mean

Full Range

µg*h/mL

Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15

ID	Title	Description
OG000	Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.15 mg/kg Q2W.
OG001	Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.5 mg/kg Q2W.
OG002	Phase 1 Dose Escalation: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.
OG003	Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q2W

Secondary

Phase 1: Observed Maximum Plasma Concentration for SNDX-6352

Blood samples were collected for determination of SNDX-6352 concentration.

Pharmacokinetic Analysis Set: All treated participants who had at least 1 plasma concentration measured. Number Analyzed = participants who were evaluable at specified timepoints

Posted

Mean

Full Range

µg/mL

Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15

ID	Title	Description
OG000	Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.15 mg/kg Q2W.
OG001	Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.5 mg/kg Q2W.
OG002	Phase 1 Dose Escalation: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.
OG003	Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 3 mg/kg Q2W.

Secondary

Phase 1: Time to Observed Maximum Plasma Concentration

Blood samples were collected for determination of SNDX-6352 concentration.

Pharmacokinetic Analysis Set: All treated participants who had at least 1 plasma concentration measured. Number Analyzed = participants who were evaluable at specified timepoints

Posted

Median

Full Range

hours

Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15

ID	Title	Description
OG000	Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.15 mg/kg Q2W.
OG001	Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.5 mg/kg Q2W.
OG002	Phase 1 Dose Escalation: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.
OG003	Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 3 mg/kg Q2W.

Secondary

Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations

Blood samples were collected for determination of serum concentrations.

Safety Analysis Set: All participants who received at least 1 dose of study treatment. Number Analyzed = participants who were evaluable at specified timepoints

Posted

Median

Full Range

pg/mL

Baseline, Cycle 1 Day 8, Day 15, predose at Cycle 2 Day 1, Cycle 4 Day 1 (28-day cycles), and end of treatment (EOT) (median duration of treatment = 7 months)

ID	Title	Description
OG000	Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.15 mg/kg Q2W.
OG001	Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.5 mg/kg Q2W.
OG002	Phase 1 Dose Escalation: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.
OG003	Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q2W

Secondary

Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++)

Blood samples were collected for determination nonclassical monocytes levels.

Safety Analysis Set: All participants who received at least 1 dose of study treatment. Number Analyzed = participants who were evaluable at specified timepoints

Posted

Median

Full Range

percent change

Baseline, Day 8, Day 15, predose at Cycle 2 Day 1, Cycle 4 Day 1, and EOT (median duration of treatment = 7 months)

ID	Title	Description
OG000	Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.15 mg/kg Q2W.
OG001	Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.5 mg/kg Q2W.
OG002	Phase 1 Dose Escalation: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.
OG003	Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 3 mg/kg Q2W.

Secondary

Phase 1: Number of Participants Positive for Anti-Drug Antibodies (ADA)

Blood samples were collected for ADA assessment. A participant was considered ADA positive if at least 1 postbaseline sample was ADA positive.

Safety Analysis Set: All participants who received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Predose on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Day 1 of each subsequent cycle through EOT plus 30 days after last dose (safety follow-up) (median duration of treatment = 7 months)

ID	Title	Description
OG000	Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.15 mg/kg Q2W.
OG001	Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.5 mg/kg Q2W.
OG002	Phase 1 Dose Escalation: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.
OG003	Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q2W

Secondary

Phase 2: Best Overall Response (BOR), as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD

Physician-reported global cGVHD activity assessment and cGVHD response determination. Best overall response was calculated as percent of participants with a response of CR or PR.

Safety Analysis Set: All participants who received at least 1 dose of study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

Day 1 of each 28-Day cycle up to Cycle 7 Day 1

ID	Title	Description
OG000	Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.

Units	Counts
Participants	OG000

Secondary

Phase 2: Failure Free Survival (FFS)

FFS was defined as the time from first dose of study intervention to unequivocal progression of cGVHD or relapse of underlying malignancy or addition of another systemic immune suppressive therapy or discontinuation of study treatment due to toxicity or death for any reason. Unequivocal progression of cGVHD is defined as treatment discontinuation due to clinical progression. The duration of FFS was evaluated using organ-specific cGVHD activity assessment form and and summarized descriptively using the Kaplan-Meier method.

Safety Analysis Set: All participants who received at least 1 dose of study treatment.

Posted

Median

95% Confidence Interval

months

From first dose of study intervention (Day 1) up to 27 months

ID	Title	Description
OG000	Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.

Units	Counts
Participants	OG000

Secondary

Phase 2: Duration of Response (DOR)

DOR was defined as the time of initial response until documented progression or start of another systemic treatment as assessed by the Kaplan-Meir method.

Participants who achieved PR or CR in the study were evaluable for DOR.

Posted

Median

95% Confidence Interval

months

Day 1 of each 28-Day cycle for up to 12 cycles

ID	Title	Description
OG000	Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.

Units	Counts
Participants	OG00018

Secondary

Phase 2: Sustained Response Rate (SRR)

SSR of CR or PR ≥20 weeks was defined as rate of CR or PR lasting for at least 20 weeks from the time of initial response.

Safety Analysis Set: All participants who received at least 1 dose of study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

Day 1 of each 28-Day cycle for up to 12 cycles

ID	Title	Description
OG000	Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.

Units	Counts
Participants	OG00023

Secondary

Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD

The percentage of participants with a response (CR/PR) in the skin, eyes, mouth, esophagus, upper gastrointestinal (GI), lower GI, liver, lungs, or joints and fascia were assessed using the NIH Consensus Development Project on Clinical Trials.

Safety Analysis Set: All participants who received at least 1 dose of study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

Day 1 of each 28-Day cycle for up to 12 cycles

ID	Title	Description
OG000	Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.

Units	Counts
Participants	OG000

Secondary

Phase 2: Number of Participants With a Joint and Fascia Response Based on Refined NIH Response Algorithm for cGVHD

Safety Analysis Set: All participants who received at least 1 dose of study treatment and who had this assessment.

Posted

Count of Participants

Participants

Day 1 of each 28-Day cycle for up to 12 cycles

ID	Title	Description
OG000	Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.

Units	Counts
Participants	OG00017

Secondary

Phase 2: Number of Participants With A Lee Symptom Scale Summary Score Decrease of at Least 7 Points From Baseline

The Lee cGVHD symptom questionnaire asked participants to indicate the degree of "bother" that they experienced during the past 7 days due to symptoms in 7 domains potentially affected by chronic GVHD (skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, emotional distress) using a 5-point Likert scale from 0 "not at all" to 4 "extremely." Scores were normalized (0 to 100 scale) and the number of participants with a ≥ 7-point decrease in normalized score was calculated. A decrease in score indicated improvement in symptoms.

Safety Analysis Set: All participants who received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Day 1 of each 28-Day cycle for up to 12 cycles

ID	Title	Description
OG000	Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.

Units	Counts
Participants	OG000

Secondary

Phase 2: Number of Participants With a ≥50% Reduction in Prednisone Equivalent Dosage Lasting at Least 28 Days

Safety Analysis Set: All participants who received at least 1 dose of study treatment and had corticosteroid usage at Cycle 1 Day 1.

Posted

Count of Participants

Participants

Day 1 of each 28-Day cycle for up to 12 cycles

ID	Title	Description
OG000	Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.

Units	Counts
Participants	OG00019

Secondary

Phase 2: Number of Participants Who Discontinued Calcineurin Inhibitor Use

Safety Analysis Set: All participants who received at least 1 dose of study treatment and had calcineurin inhibitors usage at Cycle 1 Day 1.

Posted

Count of Participants

Participants

Day 1 of each 28-Day cycle for up to 12 cycles

ID	Title	Description
OG000	Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.

Units	Counts
Participants	OG0006

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0011 affected1 at risk EG0023 affected26 at risk EG0030 affected6 at risk EG0040 affected6 at risk
Cellulitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Pyrexia	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Bronchiectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Bronchitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Face oedema	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Fatigue	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Gastroenteritis norovirus	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Hepatitis	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Hypotension	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Hypovolaemic shock	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Influenza	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Ischaemic cerebral infarction	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Klebsiella infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Lymphoedema	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Metapneumovirus infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Multiple injuries	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Oedema peripheral	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Parainfluenzae virus infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Peripheral ischaemia	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Pneumonia bacterial	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Sepsis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Septic arthritis staphylococcal	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Septic shock	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Spinal fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0011 affected1 at risk EG0020 affected26 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Thrombophlebitis superficial	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Wound infection pseudomonas	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Serratia sepsis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fatigue	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0011 affected1 at risk EG00212 affected26 at risk EG0033 affected6 at risk EG0042 affected6 at risk
Oedema peripheral	General disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0024 affected26 at risk EG003
Pyrexia	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Chills	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Malaise	General disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Gait disturbance	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Influenza like illness	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Oedema	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Pain	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Axillary pain	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Chest discomfort	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Feeling abnormal	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Injection site reaction	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Swelling face	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0026 affected26 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0025 affected26 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0011 affected1 at risk EG0024 affected26 at risk EG003
Amylase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0026 affected26 at risk EG003
Lipase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0024 affected26 at risk EG003
Blood creatinine increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0025 affected26 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Blood cholesterol increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Weight decreased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
White blood cell count decreased	Investigations	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Blood creatine phosphokinase abnormal	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Blood thyroid stimulating hormone increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
C-reactive protein	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Platelet count decreased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Red blood cell sedimentation rate increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Vitamin B1 decreased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0011 affected1 at risk EG0022 affected26 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Fluid retention	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Hyperammonaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Hypophagia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Lactic acidosis	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0011 affected1 at risk EG0028 affected26 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0028 affected26 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0011 affected1 at risk EG0023 affected26 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Faeces discoloured	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Oral disorder	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Tongue erythema	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0027 affected26 at risk EG003
COVID-19	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Cellulitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Pustule	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Bronchitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Eye infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Fungal infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Klebsiella infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Oesophageal candidiasis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Otitis externa	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Paronychia	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Pseudomonas infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Rhinovirus infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Sinusitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Skin infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Wound infection pseudomonas	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0024 affected26 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0024 affected26 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Abscess neck	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0011 affected1 at risk EG0023 affected26 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Paranasal sinus discomfort	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Periorbital oedema	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Vision blurred	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Diplopia	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Eye pain	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Cataract	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Conjunctival haemorrhage	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Eye irritation	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Lacrimation increased	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Photophobia	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Dizziness	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0026 affected26 at risk EG003
Headache	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0011 affected1 at risk EG0025 affected26 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Memory impairment	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Somnolence	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0024 affected26 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Agitation	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Depression	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Hallucination	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0011 affected1 at risk EG0021 affected26 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Ingrowing nail	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0011 affected1 at risk EG0024 affected26 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Splenomegaly	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0024 affected26 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0022 affected26 at risk EG003
Back injury	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Hand fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Procedural headache	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Vascular access complication	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Wound complication	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Hypertension	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0023 affected26 at risk EG003
Haematoma	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Flushing	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Haemorrhage	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Hot flush	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Chromaturia	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Incontinence	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Urethral prolapse	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Adrenal insufficiency	Endocrine disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Androgen deficiency	Endocrine disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003
Vulvovaginal dryness	Reproductive system and breast disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0021 affected26 at risk EG003
Varicose vein	Vascular disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected1 at risk EG0010 affected1 at risk EG0020 affected26 at risk EG003

ID	Term
D000092124	Organizing Pneumonia
D001989	Bronchiolitis Obliterans
D001988	Bronchiolitis
D001991	Bronchitis
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D006086	Graft vs Host Disease
D007154	Immune System Diseases

ID	Title	Description
BG000	Phase 1 Dose Escalation: SNDX-6352 0.15 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 at 0.15 mg/kg Q2W.
BG001	Phase 1 Dose Escalation: SNDX-6352 0.5 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.5 mg/kg Q2W.
BG002	Phase 1 Dose Escalation: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.
BG003	Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 3 mg/kg Q2W.
BG004	Phase 1 Dose Escalation: SNDX-6352 3 mg/kg Q4W	Participants received an IV infusion of SNDX-6352 3 mg/kg Q4W.
BG005	Phase 2 Dose Expansion: SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W.
BG006	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	SNDX-6352 0.15 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.15 mg/kg Q2W in Phase 1.	0	1	1	1	1	1
EG001	SNDX-6352 0.5 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 0.5 mg/kg Q2W in Phase 1.	0	1	1	1	1	1
EG002	SNDX-6352 1 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 1 mg/kg Q2W in Phases 1 and 2.	1	26	12	26	26	26
EG003	SNDX-6352 3 mg/kg Q2W	Participants received an IV infusion of SNDX-6352 3 mg/kg Q2W in Phase 1.	0	6	3	6	6	6
EG004	SNDX-6352 3 mg/kg Q4W	Participants received an IV infusion of SNDX-6352 3 mg/kg Q4W in Phase 1.	0	6	2	6	6	6