A Phase 2A Study of ALXN1007 in Participants With Newly D... | NCT02245412

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
ALXN1007 10 mg/kg once weekly	Experimental	Cohort 1, the first dosing cohort, received 10 mg/kg ALXN1007 IV once weekly for 8 weeks.	Biological: ALXN1007 10 mg/kg once weekly
ALXN1007 20 mg/kg once weekly	Experimental	Cohort 2 received 20 mg/kg ALXN1007 IV once weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.	Biological: ALXN1007 20 mg/kg once weekly
ALXN1007 20 mg/kg twice weekly	Experimental	Cohort 3 received 20 mg/kg ALXN1007 IV twice weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.	Biological: ALXN1007 20 mg/kg twice weekly

Interventions

Name	Type	Description	Arm Group Labels	Other Names
ALXN1007 10 mg/kg once weekly	Biological	ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.	ALXN1007 10 mg/kg once weekly

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Acute Graft-Versus-Host Disease (GVHD) Response Rate At Day 28	The number of participants with overall acute GVHD response was determined at Day 28. Acute Overall GVHD is defined as improvement from diagnosis in any organ by at least 1 stage, without progression in any other organ, and with no additional therapy being administered. Acute GVHD staging included skin, liver, and GI assessments, which were to be performed using the Modified Keystone Grading Schema. Deaths were considered nonresponders; otherwise last postbaseline values were carried forward for imputation of missing responses. Modified Keystone Grading Schema: Skin - Stages 0 = No Rash, 1 = Rash <25% body surface area (BSA), 2 = 25% to 50% BSA, 3 = >50% BSA, 4 = bullae, desquamation; Lower GI Tract (stool volume over 24 hours) - Stages 0 = <500 mL, 1 = 500 to 1000 mL, 2 = 1001 to 1500 mL, 3 = >1500 mL, 4 = severe abdominal pain +/- ileus, frank blood, or melena; Liver (bilirubin levels) - Stages 0 = ≤2 mg/dL, 1 = 2.1 to 3 mg/dL, 2 = 3.1 to 6 mg/dL, 3 = 6.1 to 15 mg/dL, 4 = >15 mg/dL.	Day 28

Secondary Outcomes

Measure	Description	Time Frame
Pharmacokinetics (PK): Time To Maximum Observed Concentration In Plasma (Tmax) Of IV ALXN1007	The Tmax of ALXN1007 was measured on Treatment Days 1, 28, and 49, from blood samples collected at time points relative to the dosing of ALXN1007. PK assessments were to have been measured from Baseline, Treatment Days 7, 14, 21, 28, 35, 42, 49, 56, and Follow-up Days 86, 180, and Early Termination (ET). Due to the early termination of the study and the clinical development of the ALXN1007 program, a number of PK analyses were not completed. PK data for the 20 mg/kg ALXN1007 once weekly dosing group and the 20 mg/kg ALXN1007 twice weekly dosing group are not available.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants must be males or females age 18 years or older.
Participants with Stage 1 to 4 (per the Modified Keystone Grading Schema) acute GVHD of the lower GI tract, without signs of chronic GVHD, at the time of diagnosis, which developed in the first 180 days following allogeneic hematopoietic cell transplantation (HCT) using bone marrow, peripheral blood, or cord blood; or after preplanned donor lymphocyte infusion.
Participants are willing to undergo or must have had an endoscopy of the upper and/or lower GI tract and biopsy to confirm GI GVHD.
Participants must be receiving systemic corticosteroids.
Participants with an absolute neutrophil count (ANC) >500/microliter (μL) at Screening.
Participants and spouse/partner who are of childbearing potential must be using high effective contraception consisting of 2 forms of birth control (at least 1 of which much be barrier method) starting at Screening and continuing through the entire study (for at least 3 months after the last dose of ALXN1007 if study treatment is stopped early or participant withdraws consent).
Male participants must not donate sperm during the Screening and Treatment periods, and for at least 3 months after the last dose of ALXN1007.
- Stage of acute GVHD of the lower GI tract will be determined using the Modified Keystone Grading Schema.

Exclusion Criteria:

Participants with a body weight > 140 kg (for Cohorts dosing 20 mg/kg of ALXN1007 and higher only).
Participants with signs and symptoms of chronic GVHD.
Participants with an active uncontrolled infection.
Participants who test positive for Clostridium difficile (C. difficile) at Screening.
Participants with relapsed/persistent malignancy requiring rapid immune suppression withdrawal.
Participants who received an unplanned (not part of the original transplant therapy plan) donor lymphocyte infusion.
Participants who received previous systemic treatment for acute GVHD, except for a maximum of 3 days (72 hours) of 2 mg/kg corticosteroid therapy.
Participants with unresolved veno-occlusive disease of the liver.
Participants with creatinine clearance <40 milliliters (mL)/minute at Screening, as calculated by the Cockcroft-Gault formula.
Participants known to be infected with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
Participants known to have an uncontrolled thyroid disorder.
Participants who are pregnant, breast feeding, or sexually active and unwilling to use effective birth control for the duration of the study.
Participants who participated in any other investigational drug trial or had exposure to any other investigational agent, device, or procedure <4 weeks prior to Screening and throughout the entire trial, with the exception of investigational drugs administered prophylactically for cytomegalovirus (CMV) post allogeneic HCT.

Facility	Status	City	State	ZIP	Country	Contacts
City of Hope		Duarte	California	91010	United States
Emory University Hospital

ID	Title	Description
FG000	ALXN1007 10 mg/kg Once Weekly	Cohort 1, the first dosing cohort, received 10 milligrams/kilogram (mg/kg) ALXN1007 intravenously (IV) once weekly for 8 weeks.
FG001	ALXN1007 20 mg/kg Once Weekly

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 12, 2016	Oct 23, 2018

ID	Title	Description
BG000	ALXN1007 10 mg/kg Once Weekly	Cohort 1, the first dosing cohort, received 10 mg/kg ALXN1007 IV once weekly for 8 weeks.
BG001	ALXN1007 20 mg/kg Once Weekly	Cohort 2 received 20 mg/kg ALXN1007 IV once weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.
BG002	ALXN1007 20 mg/kg Twice Weekly	Cohort 3 received 20 mg/kg ALXN1007 IV twice weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00017 BG0016 BG0022 BG00325

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

Overall Acute Graft-Versus-Host Disease (GVHD) Response Rate At Day 28

The number of participants with overall acute GVHD response was determined at Day 28. Acute Overall GVHD is defined as improvement from diagnosis in any organ by at least 1 stage, without progression in any other organ, and with no additional therapy being administered. Acute GVHD staging included skin, liver, and GI assessments, which were to be performed using the Modified Keystone Grading Schema. Deaths were considered nonresponders; otherwise last postbaseline values were carried forward for imputation of missing responses. Modified Keystone Grading Schema: Skin - Stages 0 = No Rash, 1 = Rash <25% body surface area (BSA), 2 = 25% to 50% BSA, 3 = >50% BSA, 4 = bullae, desquamation; Lower GI Tract (stool volume over 24 hours) - Stages 0 = <500 mL, 1 = 500 to 1000 mL, 2 = 1001 to 1500 mL, 3 = >1500 mL, 4 = severe abdominal pain +/- ileus, frank blood, or melena; Liver (bilirubin levels) - Stages 0 = ≤2 mg/dL, 1 = 2.1 to 3 mg/dL, 2 = 3.1 to 6 mg/dL, 3 = 6.1 to 15 mg/dL, 4 = >15 mg/dL.

Participants in the mFAS Population - In the 10 mg/kg ALXN1007 once weekly dose group, 1 participant was prematurely discontinued after receiving a single dose due to lack of confirmed GI GVHD.

Posted

Count of Participants

Participants

Day 28

ID	Title	Description
OG000	ALXN1007 10 mg/kg Once Weekly	Cohort 1, the first dosing cohort, received 10 mg/kg ALXN1007 IV once weekly for 8 weeks.
OG001	ALXN1007 20 mg/kg Once Weekly	Cohort 2 received 20 mg/kg ALXN1007 IV once weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.
OG002	ALXN1007 20 mg/kg Twice Weekly	Cohort 3 received 20 mg/kg ALXN1007 IV twice weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.

Units	Counts
Participants	OG00016 OG0016 OG0022

Title

Denominators

Categories

Title	Measurements
	OG00010 OG0013 OG0021

Secondary

Pharmacokinetics (PK): Time To Maximum Observed Concentration In Plasma (Tmax) Of IV ALXN1007

The Tmax of ALXN1007 was measured on Treatment Days 1, 28, and 49, from blood samples collected at time points relative to the dosing of ALXN1007. PK assessments were to have been measured from Baseline, Treatment Days 7, 14, 21, 28, 35, 42, 49, 56, and Follow-up Days 86, 180, and Early Termination (ET).

Due to the early termination of the study and the clinical development of the ALXN1007 program, a number of PK analyses were not completed. PK data for the 20 mg/kg ALXN1007 once weekly dosing group and the 20 mg/kg ALXN1007 twice weekly dosing group are not available.

PK population: All participants in the 10 mg/kg ALXN1007 once weekly dose group who received at least 1 dose of ALXN1007 and who had evaluable PK and pharmacodynamic (PD) data.

Posted

Median

Full Range

hours

Predose up to 72 hours postdose

ID	Title	Description
OG000	ALXN1007 10 mg/kg Once Weekly	Cohort 1, the first dosing cohort, received 10 mg/kg ALXN1007 IV once weekly for 8 weeks.
OG001	ALXN1007 20 mg/kg Once Weekly	Cohort 2 received 20 mg/kg ALXN1007 IV once weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.

Secondary

PK: Maximum Observed Concentration In Plasma (Cmax) Of IV ALXN1007

The Cmax of ALXN1007 was measured on Treatment Days 1, 28, and 49, from blood samples collected at time points relative to the dosing of ALXN1007. PK assessments were to have been measured from Baseline, Treatment Days 7, 14, 21, 28, 35, 42, 49, 56, and Follow-up Days 86, 180, and Early Termination (ET).

PK population: All participants in the 10 mg/kg ALXN1007 once weekly dose group who received at least 1 dose of ALXN1007 and who had evaluable PK and PD data.

Posted

Median

Full Range

ug/mL

Predose up to 72 hours postdose

ID	Title	Description
OG000	ALXN1007 10 mg/kg Once Weekly	Cohort 1, the first dosing cohort, received 10 mg/kg ALXN1007 IV once weekly for 8 weeks.
OG001	ALXN1007 20 mg/kg Once Weekly	Cohort 2 received 20 mg/kg ALXN1007 IV once weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.

Secondary

PK: Area Under The Plasma (Or Serum) Concentration Versus Time Curve (AUC) Of IV ALXN1007

The AUC of ALXN1007 was measured on Treatment Days 1, 28, and 49, from blood samples collected at time points relative to the dosing of ALXN1007. PK assessments were to have been measured from Baseline, Treatment Days 7, 14, 21, 28, 35, 42, 49, 56, and Follow-up Days 86, 180, and Early Termination (ET).

PK population: All participants in the 10 mg/kg ALXN1007 once weekly dose group who received at least 1 dose of ALXN1007 and who had evaluable PK and PD data.

Posted

Median

Full Range

h*ug/mL

Predose up to 72 hours postdose

ID	Title	Description
OG000	ALXN1007 10 mg/kg Once Weekly	Cohort 1, the first dosing cohort, received 10 mg/kg ALXN1007 IV once weekly for 8 weeks.
OG001	ALXN1007 20 mg/kg Once Weekly	Cohort 2 received 20 mg/kg ALXN1007 IV once weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Thrombotic microangiopathy	Blood and lymphatic system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Ascites	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Chronic gastritis	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Nausea	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Vomiting	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Asthenia	General disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Chest pain	General disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Influenza like illness	General disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Graft versus host disease	Immune system disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0021 affected2 at risk
Graft versus host disease in gastrointestinal tract	Immune system disorders	MedDRA (15.1)	Systematic Assessment	EG0004 affected17 at risk EG0012 affected6 at risk EG0022 affected2 at risk
BK virus infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Cellulitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Cytomegalovirus viraemia	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Device related infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG00011 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Encephalitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Pneumonia	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Respiratory syncytial virus infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Staphylococcal infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Urinary tract infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Post procedural complication	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.1)	Systematic Assessment	EG0003 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Precursor B-lymphoblastic lymphoma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
T-cell lymphoma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Syncope	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Mental status changes	Psychiatric disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0011 affected6 at risk EG0021 affected2 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Atrial flutter	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Bradycardia	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Sinus tachycardia	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Tachycardia	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0021 affected2 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Dry eye	Eye disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Eye pain	Eye disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Eyelid margin crusting	Eye disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Scleral hyperaemia	Eye disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Vision blurred	Eye disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Visual impairment	Eye disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Vitreous degeneration	Eye disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Vitreous detachment	Eye disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Anal incontinence	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Ascites	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Constipation	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Dry mouth	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Flatulence	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0021 affected2 at risk
Ileus	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Nausea	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Vomiting	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Asthenia	General disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Chest pain	General disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Chills	General disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Device related thrombosis	General disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Fatigue	General disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0021 affected2 at risk
Oedema	General disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Oedema peripheral	General disorders	MedDRA (15.1)	Systematic Assessment	EG0007 affected17 at risk EG0012 affected6 at risk EG0021 affected2 at risk
Peripheral swelling	General disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Pyrexia	General disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0012 affected6 at risk EG0020 affected2 at risk
Jaundice	Hepatobiliary disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Graft versus host disease in skin	Immune system disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Hypersensitivity	Immune system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Hypogammaglobulinaemia	Immune system disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0021 affected2 at risk
Adenovirus infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
BK virus infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Bacteraemia	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Bronchopulmonary aspergillosis	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Candida infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Cellulitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Colitis herpes	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Corona virus infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Cytomegalovirus colitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Cytomegalovirus infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Cytomegalovirus viraemia	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Enterococcal bacteraemia	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Enterococcal infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Epstein-Barr viraemia	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Epstein-Barr virus infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Folliculitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Human herpesvirus 6 infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Influenza	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Pneumonia	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Respiratory syncytial virus infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Rotavirus infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Sepsis	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Sinusitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Staphylococcal infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Urinary tract infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0021 affected2 at risk
Urinary tract infection enterococcal	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Urinary tract infection staphylococcal	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Wound	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Alanine aminotransferase increased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Blood creatinine increased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Blood immunoglobulin G decreased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Lymphocyte count decreased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Neutrophil count decreased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0021 affected2 at risk
Transaminases increased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Weight decreased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0012 affected6 at risk EG0020 affected2 at risk
White blood cell count decreased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0013 affected6 at risk EG0020 affected2 at risk
White blood cell count increased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Glucose tolerance impaired	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0012 affected6 at risk EG0021 affected2 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0012 affected6 at risk EG0020 affected2 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0003 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0011 affected6 at risk EG0021 affected2 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0021 affected2 at risk
Akathisia	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Dizziness	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Dysgeusia	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Headache	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Lethargy	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Paraesthesia	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Somnolence	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Tardive dyskinesia	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Tremor	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Agitation	Psychiatric disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Anxiety	Psychiatric disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Confusional state	Psychiatric disorders	MedDRA (15.1)	Systematic Assessment	EG0003 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Depression	Psychiatric disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Depressive symptom	Psychiatric disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Hallucination, visual	Psychiatric disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Insomnia	Psychiatric disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Micturition urgency	Renal and urinary disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Vulvovaginal discomfort	Reproductive system and breast disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0012 affected6 at risk EG0020 affected2 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0020 affected2 at risk
Haematoma	Vascular disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Hypertension	Vascular disorders	MedDRA (15.1)	Systematic Assessment	EG0003 affected17 at risk EG0010 affected6 at risk EG0021 affected2 at risk
Hypotension	Vascular disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0011 affected6 at risk EG0021 affected2 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk
Cystitis viral	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected17 at risk EG0010 affected6 at risk EG0020 affected2 at risk

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	ALXN1007 10 mg/kg Once Weekly	Cohort 1, the first dosing cohort, received 10 mg/kg ALXN1007 IV once weekly for 8 weeks.	6	17	13	17	17	17
EG001	ALXN1007 20 mg/kg Once Weekly	Cohort 2 received 20 mg/kg ALXN1007 IV once weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.	3	6	4	6	6	6
EG002	ALXN1007 20 mg/kg Twice Weekly	Cohort 3 received 20 mg/kg ALXN1007 IV twice weekly for 8 weeks. For the first 2 participants enrolled, the first ALXN1007 dose was not to be administered on the same day and a safety and tolerability review was to take place after the second (and prior to the third) ALXN1007 dose for each participant. If the ALXN1007 dose was determined to be sufficiently tolerated by the participant, dosing was to continue for that participant. For any other participants enrolled in the dosing cohort, participants were not to proceed to the third ALXN1007 dose prior to the completion of the safety and tolerability review (of the first 2 doses) for the first 2 participants.	1	2	2	2	2	2