Ravulizumab Subcutaneous (SC) Versus Ravulizumab Intraven... | NCT03748823

ID	Type	Description	Link
2017-002370-39	EudraCT Number

Label	Type	Description	Intervention Names
Ravulizumab SC Treatment Group	Experimental	In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by SC maintenance doses of ravulizumab administered via the ravulizumab OBDS on Day 15 and every week (qw) thereafter for a total of 10 weeks of study treatment. In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.	Combination Product: Ravulizumab OBDS Biological: Ravulizumab
Ravulizumab IV Treatment Group	Active Comparator	In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by IV maintenance doses of ravulizumab on Day 15. In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.	Combination Product: Ravulizumab OBDS Biological: Ravulizumab

Name	Type	Description	Arm Group Labels	Other Names
Ravulizumab OBDS	Combination Product	The ravulizumab OBDS is a biological-device combination product consisting of a prefilled cartridge containing ravulizumab SC and an on-body injector.

Measure	Description	Time Frame
Ctrough Serum Concentration of Ravulizumab		Predose at Day 71

Measure	Description	Time Frame
Ctrough Serum Concentration of Ravulizumab at Day 351		Predose at Day 351
Free Serum Complement Component 5 (C5) Concentrations at Day 71		Predose at Day 71

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female ≥18 years of age
Treated with eculizumab for PNH for at least 3 months prior to Day 1
LDH level ≤1.5 × upper limit of normal (ULN) at screening
PNH diagnosis confirmed by documented high-sensitivity flow cytometry.
Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
Body weight ≥40 to <100 kilogram (kg)
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.
Willing and able to give written informed consent and comply with study visit schedule.

Exclusion Criteria:

More than 1 LDH value > 2 × ULN within the 3 months prior to study entry
History of bone marrow transplantation.
History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the Investigator or Sponsor, would preclude participation.
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).
Females who are pregnant, breastfeeding or who have a positive pregnancy test at screening or Day 1.
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.

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Los Angeles	California	90089	United States
Research Site

PubMed Identifier	Type	Citation	Retractions
36272026	Derived	Yenerel MN, Sicre de Fontbrune F, Piatek C, Sahin F, Fureder W, Ortiz S, Ogawa M, Ozol-Godfrey A, Sierra JR, Szer J. Phase 3 Study of Subcutaneous Versus Intravenous Ravulizumab in Eculizumab-Experienced Adult Patients with PNH: Primary Analysis and 1-Year Follow-Up. Adv Ther. 2023 Jan;40(1):211-232. doi: 10.1007/s12325-022-02339-3. Epub 2022 Oct 22.

Label	URL
Related Info	View source

ID	Title	Description
FG000	Ravulizumab Intravenous (IV)/Subcutaneous (SC) Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 milligrams [mg]) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC once every week (qw).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 8, 2021	Aug 9, 2022

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

Ctrough Serum Concentration of Ravulizumab

Pharmacokinetic (PK) analysis set included all participants who had evaluable PK data.

Posted

Mean

Standard Deviation

micrograms/milliliter (µg/mL)

Predose at Day 71

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Units	Counts
Participants	OG00043 OG00170

Title

Denominators

Categories

Title	Measurements
	OG000457.58± 108.491 OG001578.70± 140.819

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		ANOVA		<0.0001	Analysis of variance (ANOVA) was performed on log-transformed Ctrough and included treatment and stratified weight group as fixed effects.	Ratio of Geometric Least Squares Mean	1.257			2-Sided	90	1.160	1.361			Geometric least squares mean are the least squares mean from the mixed model after back transformation to the original scale. The 90% confidence interval is presented after back transformation to the original scale.		Non-Inferiority	Noninferiority was determined based on the 90% Confidence interval calculated from the combination z-score that accounts for the interim analysis.

Secondary

Ctrough Serum Concentration of Ravulizumab at Day 351

SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

µg/mL

Predose at Day 351

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Units	Counts

Secondary

Free Serum Complement Component 5 (C5) Concentrations at Day 71

Pharmacodynamic (PD) analysis set included all participants who received at least 1 dose of ravulizumab and who had evaluable PD data. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

µg/mL

Predose at Day 71

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Units	Counts
Participants

Secondary

Free Serum Complement Component 5 (C5) Concentrations at Day 351

Posted

Mean

Standard Deviation

µg/mL

Predose at Day 351

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Units	Counts

Secondary

Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71

Baseline was defined as the last assessment prior to first study drug dose. LDH samples impacted by tabletop hemolysis were excluded from the analysis.

Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

percent change

Baseline, Day 71

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Secondary

Percent Change From Baseline in LDH Levels at Day 351

SC baseline was defined as the last assessment prior to first dose of SC treatment. LDH samples impacted by tabletop hemolysis were excluded from the analysis.

Posted

Mean

Standard Deviation

percent change

Baseline, Day 351

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Secondary

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71

FACIT-fatigue subscale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days. Items are scored on a 5 point Likert-type scale. Item scores ranged from 0 ("not at all") to 4 ("very much"). The total, summed score ranged from 0 to 52; lower scores indicating greater fatigue and higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of study drug.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Day 71

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Secondary

Change From Baseline in FACIT-Fatigue Scale Version 4 Score at Day 351

Posted

Mean

Standard Deviation

units on a scale

Baseline, Day 351

ID	Title	Description
OG000	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Units

Secondary

Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71

The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Day 71

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Secondary

Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351

SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure. This outcome measure was planned to be reported for ravulizumab SC/SC treatment group only.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Day 351

ID	Title	Description
OG000	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Secondary

Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71

Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 grams/deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2*upper limit of normal (ULN). Denominator for a percentage was participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess breakthrough hemolysis.

Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline up to Day 71

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Secondary

Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351

Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 g/dL], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2*ULN. Denominator for a percentage was participants with at least one post-baseline data for the period.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline up to Day 351

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Secondary

Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71

Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Percentages are based on participants with any post-baseline data for the period. For Through Day 71, only visits with data were used to assess transfusion avoidance.

Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline up to Day 71

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Secondary

Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351

Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline up to Day 351

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Secondary

Percentage of Participants Who Maintained Stabilized Hemoglobin (SHg) up to Day 71

SHg was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from Baseline (defined as the last assessment prior to the first dose of the study drug) in the absence of transfusion to the end of the period of interest. Percentages were based on participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess SHg.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline up to Day 71

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Secondary

Percentage of Participants Who Maintained SHg up to Day 351

SHg was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from SC Baseline (defined as the last assessment prior to the first dose of SC treatment) in the absence of transfusion to the end of the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period. Visits were based on the number of days since first dose of SC treatment.

SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline up to Day 351

ID	Title	Description
OG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
OG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 23.1	Non-systematic Assessment		EG0001 affected45 at risk EG0012 affected84 at risk
Haemolysis	Blood and lymphatic system disorders	MedDRA 23.1	Non-systematic Assessment		EG0000 affected45 at risk EG0015 affected84 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 23.1	Non-systematic Assessment		EG0001 affected45 at risk EG0011 affected84 at risk
Aplastic anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0012 affected84 at risk
Haemolytic anaemia	Blood and lymphatic system disorders	MedDRA 23.1	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 23.1	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Lens dislocation	Eye disorders	MedDRA 23.1	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Gastritis	Gastrointestinal disorders	MedDRA 23.1	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Pyrexia	General disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0011 affected84 at risk
Application site induration	General disorders	MedDRA 23.1	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Fatigue	General disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 26.0	Non-systematic Assessment		EG0002 affected45 at risk EG0011 affected84 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
COVID-19	Infections and infestations	MedDRA 23.1	Non-systematic Assessment		EG0002 affected45 at risk EG0016 affected84 at risk
Bacterial infection	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Bacterial sepsis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0012 affected84 at risk
Gastroenteritis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0011 affected84 at risk
Hepatitis viral	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Salmonellosis	Infections and infestations	MedDRA 23.1	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Sinusitis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Suspected COVID-19	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Tubo-ovarian abscess	Infections and infestations	MedDRA 26.0	Non-systematic Assessment	This adverse event is gender specific.	EG0000 affected25 at risk EG0011 affected44 at risk
Procedural hypotension	Injury, poisoning and procedural complications	MedDRA 23.1	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Transfusion reaction	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Colorectal adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.1	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Cervicobrachial syndrome	Nervous system disorders	MedDRA 23.1	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Depression	Psychiatric disorders	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Urinary retention	Renal and urinary disorders	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Adnexal torsion	Reproductive system and breast disorders	MedDRA 26.0	Non-systematic Assessment	This adverse event is gender specific.	EG0000 affected25 at risk EG0011 affected44 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0012 affected84 at risk
Breakthrough haemolysis	Blood and lymphatic system disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Malaise	General disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0011 affected84 at risk
Anal abscess	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Appendicitis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Dengue haemorrhagic fever	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Influenza	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Localised infection	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Osteomyelitis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Immunisation reaction	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Breast cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Fibroadenoma of breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Metastatic uterine cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Psychiatric decompensation	Psychiatric disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Angina pectoris	Cardiac disorders	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0011 affected84 at risk
Arrhythmia	Cardiac disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0010 affected84 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 23.1	Non-systematic Assessment		EG0004 affected45 at risk EG00112 affected84 at risk
Haemolysis	Blood and lymphatic system disorders	MedDRA 26.0	Non-systematic Assessment		EG0004 affected45 at risk EG00110 affected84 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG00117 affected84 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.0	Non-systematic Assessment		EG0006 affected45 at risk EG00110 affected84 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.0	Non-systematic Assessment		EG0005 affected45 at risk EG0019 affected84 at risk
Vomiting	Gastrointestinal disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0017 affected84 at risk
Constipation	Gastrointestinal disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0016 affected84 at risk
Pyrexia	General disorders	MedDRA 23.1	Non-systematic Assessment		EG0007 affected45 at risk EG00120 affected84 at risk
Asthenia	General disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG00113 affected84 at risk
Influenza like illness	General disorders	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0017 affected84 at risk
Injection site erythema	General disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0017 affected84 at risk
Fatigue	General disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0017 affected84 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0014 affected84 at risk
COVID-19	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG00016 affected45 at risk EG00139 affected84 at risk
Nasopharyngitis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0008 affected45 at risk EG00111 affected84 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0015 affected84 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG00111 affected84 at risk
Influenza	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0006 affected45 at risk EG00110 affected84 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Non-systematic Assessment		EG0005 affected45 at risk EG00111 affected84 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0017 affected84 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Non-systematic Assessment		EG0005 affected45 at risk EG0019 affected84 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Non-systematic Assessment		EG0000 affected45 at risk EG0017 affected84 at risk
Headache	Nervous system disorders	MedDRA 26.0	Non-systematic Assessment		EG00014 affected45 at risk EG00116 affected84 at risk
Dizziness	Nervous system disorders	MedDRA 26.0	Non-systematic Assessment		EG0004 affected45 at risk EG0015 affected84 at risk
Device delivery system issue	Product Issues	MedDRA 26.0	Non-systematic Assessment	Adverse Events relating to drug delivery were coded to the MedDRA SOC of "Product Issues", including missing dose (ie, no dose) and partial dose (ie, less than full volume of dose administered) medication errors occurring with use of device.	EG00042 affected45 at risk EG00174 affected84 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Non-systematic Assessment		EG0006 affected45 at risk EG0016 affected84 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Non-systematic Assessment		EG0004 affected45 at risk EG0016 affected84 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0012 affected84 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Non-systematic Assessment		EG0002 affected45 at risk EG0016 affected84 at risk
Toothache	Gastrointestinal disorders	MedDRA 26.0	Non-systematic Assessment		EG0004 affected45 at risk EG00110 affected84 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0011 affected84 at risk
Infusion site erythema	General disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0014 affected84 at risk
Gastroenteritis	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0005 affected45 at risk EG0015 affected84 at risk
Paronychia	Infections and infestations	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0011 affected84 at risk
Post vaccination fever	Injury, poisoning and procedural complications	MedDRA 26.0	Non-systematic Assessment		EG0004 affected45 at risk EG0016 affected84 at risk
Insomnia	Psychiatric disorders	MedDRA 26.0	Non-systematic Assessment		EG0002 affected45 at risk EG0015 affected84 at risk
Anxiety	Psychiatric disorders	MedDRA 26.0	Non-systematic Assessment		EG0001 affected45 at risk EG0015 affected84 at risk
Depression	Psychiatric disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0012 affected84 at risk
Haemoglobinuria	Renal and urinary disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0011 affected84 at risk
Intermenstrual bleeding	Reproductive system and breast disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0011 affected84 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0012 affected84 at risk
Hypertension	Vascular disorders	MedDRA 26.0	Non-systematic Assessment		EG0003 affected45 at risk EG0013 affected84 at risk

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

ID	Title	Description
BG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
BG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ravulizumab IV/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	2	45	16	45	44	45
EG001	Ravulizumab SC/SC Treatment Group	During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.	2	84	30	84	83	84