ALXN1210 (Ravulizumab) Versus Eculizumab in Complement In... | NCT02946463

NCT02946463

ID	Type	Description	Link
2016-002025-11

Status Module

Description Module

Arms/Interventions Module

Label	Type	Description	Intervention Names
Ravulizumab	Experimental		Biological: Ravulizumab
Eculizumab	Active Comparator		Biological: Ravulizumab Biological: Eculizumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Ravulizumab	Biological	All treatments were given as intravenous (IV) infusions. For participants weighing ≥40 to <60 kilogram (kg): 2400 mg was given as a single loading dose, followed by 3000 mg as maintenance dose. For participants weighing ≥60 to <100 kg: 2700 mg was given as a loading dose, followed by 3300 mg as maintenance dose. For participants weighing ≥100 kg: 3000 mg was given as a loading dose, followed by 3600 mg as maintenance dose.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Proportion Of Participants With Normalization Of Lactate Dehydrogenase (LDH) Levels	LDH is an indicator of intravascular hemolysis that occurs in participants with paroxysmal nocturnal hemoglobinuria (PNH). A decrease in LDH from above the upper limit of normal (ULN) to below the ULN indicates reduction (improvement) in hemolysis. Normalization of LDH levels (LDH-N) was LDH levels less than or equal to 1 x ULN, from Day 29 through Day 183. The ULN for LDH is 246 U/L.	Day 29 through Day 183
Percentage Of Participants Who Achieved Transfusion Avoidance (TA)	Transfusion avoidance was defined as the percentage of participants who remained transfusion free and did not require a transfusion per protocol-specified guidelines through Day 183.	Baseline through Day 183

Secondary Outcomes

Measure	Description	Time Frame
Percentage Of Participants With Breakthrough Hemolysis (BTH)	Breakthrough hemolysis was defined as at least 1 new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 gram/deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 × ULN, after prior LDH reduction to <1.5 × ULN on therapy.

Eligibility Module

Eligibility Criteria

Criteria For Patient Cohort Originally Enrolled in ALXN1210-PNH-301 Study: Inclusion Criteria: 1. Male or female ≥18 years of age. 2. PNH diagnosis confirmed by documented by high-sensitivity flow cytometry. 3. Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia (hemoglobin <10 gram/deciliter), history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of packed red blood cells (pRBC) transfusion due to PNH. 4. Lactate dehydrogenase (LDH) level ≥1.5 times the upper limit of normal at screening. 5. Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment. 6. Female participants of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab. 7. Willing and able to give written informed consent and comply with study visit schedule. Exclusion Criteria: 1. Treatment with a complement inhibitor at any time. 2. History of bone marrow transplantation. 3. Body weight <40 kg. 4. Females who are pregnant, breastfeeding, or who have a positive pregnancy test at screening or Day 1. 5. Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater. 6. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation. 7. Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH). Eligibility Criteria For Roll-over Cohort: 1. All participants regardless of age, who are currently receiving ALXN1210 IV in an ongoing ALXN1210 study in patients with PNH 2. Participants must be willing and able to give written informed consent and to comply with all Extension study visits and procedures, including the use of any data collection device(s) to directly record patient data 3. Females of childbearing potential and male patients with female partners of childbearing potential must use highly effective contraception continuing until at least 8 months after the last dose of ravulizumab.

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Los Angeles	California	90033	United States
Research Site

PubMed Identifier	Type	Citation	Retractions
30510080	Background	Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, Pessoa V, Gualandro S, Fureder W, Ptushkin V, Rottinghaus ST, Volles L, Shafner L, Aguzzi R, Pradhan R, Schrezenmeier H, Hill A. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019 Feb 7;133(6):530-539. doi: 10.1182/blood-2018-09-876136. Epub 2018 Dec 3.
37804344

Label	URL
Related Info	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Ravulizumab/Ravulizumab	Participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg on Day 1. Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Day 15 and every 8 weeks thereafter for 26 weeks. After completion of the Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 5 years.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 12, 2021	Feb 27, 2024

Arm/Group Information

ID	Title	Description
BG000	Ravulizumab/Ravulizumab	Participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg on Day 1. Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Day 15 and every 8 weeks thereafter for 26 weeks. After completion of the Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 5 years.
BG001	Eculizumab/Ravulizumab	Participants received 600 mg of eculizumab on Days 1, 8, 15, and 22, followed by 900 mg of eculizumab on Day 29 and every 2 weeks thereafter for 26 weeks. After completion of the Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 5 years.
BG002	Roll-Over Cohort: Ravulizumab - Adults	Participants in this group rolled over from other ongoing studies of ravulizumab intravenous in participants with PNH into the extension period of this study and received weight-based doses of ravulizumab for up to 5 years.
BG003	Roll-Over Cohort: Ravulizumab - Pediatrics	Participants in this group rolled over from other ongoing studies of ravulizumab intravenous in participants with PNH into the extension period of this study and received weight-based doses of ravulizumab for up to 5 years.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00060 BG00152 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0005 BG00113 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0011 BG002

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

Proportion Of Participants With Normalization Of Lactate Dehydrogenase (LDH) Levels

LDH is an indicator of intravascular hemolysis that occurs in participants with paroxysmal nocturnal hemoglobinuria (PNH). A decrease in LDH from above the upper limit of normal (ULN) to below the ULN indicates reduction (improvement) in hemolysis. Normalization of LDH levels (LDH-N) was LDH levels less than or equal to 1 x ULN, from Day 29 through Day 183. The ULN for LDH is 246 U/L.

Full Analysis Set: All participants who received at least 1 dose of study drug (ravulizumab or eculizumab) and had at least 1 efficacy assessment after the first infusion of study drug.

Posted

Number

95% Confidence Interval

proportion of participants

Day 29 through Day 183

ID	Title	Description
OG000	Ravulizumab	Participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg on Day 1. Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Day 15 and every 8 weeks thereafter for 26 weeks.
OG001	Eculizumab	Participants received 600 mg of eculizumab on Days 1, 8, 15, and 22, followed by 900 mg of eculizumab on Day 29 and every 2 weeks thereafter for 26 weeks.

Units	Counts
Participants	OG000125 OG001121

Title

Denominators

Categories

Title	Measurements
	OG0000.536(0.459 to 0.612) OG0010.494(0.417 to 0.570)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A minimum of 142 participants were estimated to provide 80% power to demonstrate noninferiority of ravulizumab to eculizumab.					Odds Ratio (OR)	1.187			2-Sided	95	0.796	1.769					Non-Inferiority	LDH-N was analyzed using a generalized estimating equation (GEE) approach. The model included the following terms: treatment group, history of transfusion (as a categorical variable based on the stratification factor levels), and baseline LDH level (as a continuous variable). Noninferiority margin was based on the lower bound of the 95% confidence interval (CI) for the odds ratio (OR) of ravulizumab versus eculizumab for LDH normalization being greater than an OR of 0.39.

Primary

Percentage Of Participants Who Achieved Transfusion Avoidance (TA)

Transfusion avoidance was defined as the percentage of participants who remained transfusion free and did not require a transfusion per protocol-specified guidelines through Day 183.

Full Analysis Set: All participants who received at least 1 dose of study drug (ravulizumab or eculizumab) and had at least 1 efficacy assessment after the first infusion of study drug.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline through Day 183

ID	Title	Description
OG000	Ravulizumab	Participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg on Day 1. Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Day 15 and every 8 weeks thereafter for 26 weeks.
OG001	Eculizumab	Participants received 600 mg of eculizumab on Days 1, 8, 15, and 22, followed by 900 mg of eculizumab on Day 29 and every 2 weeks thereafter for 26 weeks.

Units	Counts
Participants

Secondary

Percentage Of Participants With Breakthrough Hemolysis (BTH)

Breakthrough hemolysis was defined as at least 1 new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 gram/deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 × ULN, after prior LDH reduction to <1.5 × ULN on therapy.

Full Analysis Set: All participants who received at least 1 dose of study drug (ravulizumab or eculizumab) and had at least 1 efficacy assessment after the first infusion of study drug.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline through Day 183

ID	Title	Description
OG000	Ravulizumab	Participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg on Day 1. Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Day 15 and every 8 weeks thereafter for 26 weeks.
OG001	Eculizumab	Participants received 600 mg of eculizumab on Days 1, 8, 15, and 22, followed by 900 mg of eculizumab on Day 29 and every 2 weeks thereafter for 26 weeks.

Secondary

Percent Change From Baseline In LDH Levels

Baseline is defined as the average of all available assessments of LDH levels prior to first study drug dose. Estimates are based on Mixed Model for Repeated Measures (MMRM) that includes treatment group, history of transfusion (as a categorical variable based on the stratification factor levels) and baseline LDH level (as a continuous variable), study visit and study visit by treatment group interaction. An unstructured covariance structure was used.

Full Analysis Set: All participants who received at least 1 dose of study drug (ravulizumab or eculizumab) and had at least 1 efficacy assessment after the first infusion of study drug.

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Day 183

ID	Title	Description
OG000	Ravulizumab	Participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg on Day 1. Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Day 15 and every 8 weeks thereafter for 26 weeks.
OG001	Eculizumab	Participants received 600 mg of eculizumab on Days 1, 8, 15, and 22, followed by 900 mg of eculizumab on Day 29 and every 2 weeks thereafter for 26 weeks.

Secondary

Change From Baseline In Quality Of Life As Assessed By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue

FACIT-Fatigue score ranges from 0 to 52, with a higher score indicating less fatigue. Baseline is defined as the last non-missing value prior to first dose of study drug. Estimates are based on MMRM that includes treatment group, the observed stratification randomization indicators (history of transfusion and LDH) and baseline FACIT-Fatigue level, study visit, and study visit by treatment group interaction. An unstructured covariance structure was used.

Full Analysis Set: All participants who received at least 1 dose of study drug (ravulizumab or eculizumab) and had at least 1 efficacy assessment after the first infusion of study drug.

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

Baseline, Day 183

ID	Title	Description
OG000	Ravulizumab	Participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg on Day 1. Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Day 15 and every 8 weeks thereafter for 26 weeks.
OG001	Eculizumab	Participants received 600 mg of eculizumab on Days 1, 8, 15, and 22, followed by 900 mg of eculizumab on Day 29 and every 2 weeks thereafter for 26 weeks.

Secondary

Percentage Of Participants With Stabilized Hemoglobin Levels

Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion through Day 183.

Full Analysis Set: All participants who received at least 1 dose of study drug (ravulizumab or eculizumab) and had at least 1 efficacy assessment after the first infusion of study drug.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline through Day 183

ID	Title	Description
OG000	Ravulizumab	Participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg on Day 1. Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Day 15 and every 8 weeks thereafter for 26 weeks.
OG001	Eculizumab	Participants received 600 mg of eculizumab on Days 1, 8, 15, and 22, followed by 900 mg of eculizumab on Day 29 and every 2 weeks thereafter for 26 weeks.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ravulizumab: Primary Evaluation	Participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg on Day 1. Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Day 15 and every 8 weeks thereafter for 26 weeks.	0	125	11	125	87	125
EG001	Eculizumab: Primary Evaluation	Participants received 600 mg of eculizumab on Days 1, 8, 15, and 22, followed by 900 mg of eculizumab on Day 29 and every 2 weeks thereafter for 26 weeks.	0	121	9	121	86	121
EG002	Ravulizumab/Ravulizumab: Extension Period	After completion of the Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 5 years.	4	124	52	124	102	124
EG003	Eculizumab/Ravulizumab: Extension Period	After completion of the Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 5 years.	4	119	43	119	100	119
EG004	Ravulizumab-Adults	Participants in this group rolled over from other ongoing studies of ravulizumab intravenous in participants with PNH into the extension period of this study and received weight-based doses of ravulizumab for up to 5 years.	0	24	2	24	13	24
EG005	Ravulizumab-Pediatrics	Participants in this group rolled over from other ongoing studies of ravulizumab intravenous in participants with PNH into the extension period of this study and received weight-based doses of ravulizumab for up to 5 years.	0	2	0	2	0	2

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected125 at risk EG0010 affected121 at risk EG0027 affected124 at risk EG0032 affected119 at risk EG0040 affected24 at risk EG0050 affected2 at risk
Aplastic anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected125 at risk EG0010 affected121 at risk EG0025 affected124 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Left ventricular failure	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Neutropenic colitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0011 affected121 at risk EG0020 affected124 at risk EG003
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected125 at risk EG0012 affected121 at risk EG0024 affected124 at risk EG003
Abscess limb	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0011 affected121 at risk EG0021 affected124 at risk EG003
Cellulitis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0011 affected121 at risk EG0020 affected124 at risk EG003
Infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0011 affected121 at risk EG0020 affected124 at risk EG003
Leptospirosis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Pneumonia	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0011 affected121 at risk EG0025 affected124 at risk EG003
Systemic infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0001 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0011 affected121 at risk EG0022 affected124 at risk EG003
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0011 affected121 at risk EG0020 affected124 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment	This is a sex-specific adverse event that only affects female participants.	EG0001 affected60 at risk EG0010 affected52 at risk EG0021 affected124 at risk EG003
Paroxysmal nocturnal haemoglobinuria	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0011 affected121 at risk EG0021 affected124 at risk EG003
Renal colic	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 26.0	Systematic Assessment		EG0001 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Breakthrough haemolysis	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0022 affected124 at risk EG003
Haemolysis	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0024 affected124 at risk EG003
Haemolytic anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0022 affected124 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Branchial cyst	Congenital, familial and genetic disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Abdominal hernia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Gastric varices	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Obstructive pancreatitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Chest discomfort	General disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0022 affected124 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Allergy to vaccine	Immune system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Appendicitis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Atypical pneumonia	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Chikungunya virus infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Coronavirus infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0026 affected124 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0023 affected124 at risk EG003
Cystitis escherichia	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Dengue fever	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Diarrhoea infectious	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Endometritis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Endophthalmitis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Enterocolitis infectious	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Erysipelas	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0022 affected124 at risk EG003
Fungal endocarditis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Furuncle	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0022 affected124 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Influenza	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Intracranial infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Meningococcal sepsis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Pulmonary sepsis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Pyelonephritis acute	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Sepsis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0022 affected124 at risk EG003
Septic shock	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Sinusitis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Incisional hernia	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0001 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Injury	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Haemochromatosis	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Adenocarcinoma gastric	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Sinonasal papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Cerebral venous thrombosis	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Intracranial pressure increased	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Migraine	Nervous system disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0022 affected124 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Nasal septum deviation	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Jugular vein thrombosis	Vascular disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Peripheral artery thrombosis	Vascular disorders	MedDRA 26.0	Systematic Assessment		EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0007 affected125 at risk EG0017 affected121 at risk EG00210 affected124 at risk EG00312 affected119 at risk EG0042 affected24 at risk EG0050 affected2 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00010 affected125 at risk EG0015 affected121 at risk EG00214 affected124 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00011 affected125 at risk EG00110 affected121 at risk EG0028 affected124 at risk EG003
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment	EG0006 affected125 at risk EG00111 affected121 at risk EG00222 affected124 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG00011 affected125 at risk EG00120 affected121 at risk EG00214 affected124 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG00013 affected125 at risk EG0017 affected121 at risk EG00230 affected124 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0009 affected125 at risk EG0018 affected121 at risk EG0020 affected124 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG00011 affected125 at risk EG00111 affected121 at risk EG00217 affected124 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0008 affected125 at risk EG0016 affected121 at risk EG00212 affected124 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0009 affected125 at risk EG0019 affected121 at risk EG0024 affected124 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0009 affected125 at risk EG0016 affected121 at risk EG0020 affected124 at risk EG003
Dizziness	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0009 affected125 at risk EG0017 affected121 at risk EG0024 affected124 at risk EG003
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00045 affected125 at risk EG00140 affected121 at risk EG00216 affected124 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0004 affected125 at risk EG0018 affected121 at risk EG00214 affected124 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0008 affected125 at risk EG0016 affected121 at risk EG0020 affected124 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected125 at risk EG0016 affected121 at risk EG0024 affected124 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0027 affected124 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0029 affected124 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0028 affected124 at risk EG003
Palpitations	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0007 affected125 at risk EG0012 affected121 at risk EG0020 affected124 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG00210 affected124 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG00210 affected124 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0005 affected125 at risk EG0016 affected121 at risk EG0028 affected124 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0027 affected124 at risk EG003
Asthenia	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Chest pain	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0028 affected124 at risk EG003
Fatigue	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0025 affected124 at risk EG003
Bronchitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0023 affected124 at risk EG003
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG00219 affected124 at risk EG003
Cystitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0028 affected124 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0023 affected124 at risk EG003
Influenza	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0029 affected124 at risk EG003
Oral herpes	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0025 affected124 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0028 affected124 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0029 affected124 at risk EG003
C-reactive protein increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0022 affected124 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG00212 affected124 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected125 at risk EG0016 affected121 at risk EG00211 affected124 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0024 affected124 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0004 affected125 at risk EG0016 affected121 at risk EG0020 affected124 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0021 affected124 at risk EG003
Hypertension	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected125 at risk EG0010 affected121 at risk EG0027 affected124 at risk EG003

ID	Term
D000743	Anemia, Hemolytic
D000740	Anemia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D009190	Myelodysplastic Syndromes
D001855	Bone Marrow Diseases