A Study Evaluating the Efficacy and Safety of Crovalimab... | NCT04434092

NCT04434092

ID	Type	Description	Link
2019-004931-21	EudraCT Number
2023-506498-36-00	EU Trial (CTIS) Number

Status Module

Sponsor/Collaborators Module

Name	Class
Chugai Pharmaceutical	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A (Crovalimab)	Experimental	Crovalimab will be administered at an initial loading dose of 1000 milligrams (mg) (for participants with body weight between 40 and 100 kilograms [kg]) or 1500 mg (for participants with body weight ≥ 100 kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab will be administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100 kg) or 1020 mg (for participants with body weight ≥ 100 kg) once every 4 weeks (Q4W) from Week 5 for a total of 24 weeks of study treatment. Participants may continue to receive crovalimab after 24 weeks of treatment up to maximum of 5 years.	Drug: Crovalimab
Arm B (Eculizumab)	Active Comparator	Participants will receive loading dose of eculizumab 600 mg on Days 1, 8, 15, and 22, followed by maintenance dose of 900 mg on Day 29 and every 2 weeks (Q2W) thereafter until 24 weeks. Participants may switch to receive crovalimab after 24 weeks of eculizumab treatment.	Drug: Crovalimab Drug: Eculizumab
Arm C (Crovalimab) (Exploratory)	Experimental	Participants with a body weight ≥ 5 to <12 kg will receive a loading series of crovalimab doses comprised of an IV dose on Day 1 of Week 1, followed by crovalimab SC dose on Day 2 Week 1. Maintenance doses will begin at Week 3 and will be administered Q2W, thereafter. Participants with a body weight ≥ 12 to < 20 kg and ≥ 20 kg will receive a loading series of crovalimab doses comprised of an IV dose on Day 1 of Week 1, followed by weekly crovalimab SC doses for 4 weeks at Week 1 (Day 2) and then at Weeks 2, 3, and 4. Maintenance doses will begin at Week 5 and will be administered Q2W thereafter, for participants with a body weight ≥ 12 to < 20 kg and Q4W thereafter, for participants with a body weight > 20 kg. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Crovalimab	Drug	Dosing depends on body weight. Participants will be dosed as follows: 5 kg to < 12 kg: 100 mg IV on Week 1 Day 1 (W1D1); 85 mg SC on Week 1 Day 2 (W1D2) and Q2W from Week 3 until end of study 12 kg to < 20 kg: 200 mg IV on W1D1; 85 mg SC on W1D2, Weeks 2, 3 and 4; 170 mg SC, Q2W from Week 5 until end of study 20 kg to < 30 kg: 300 mg IV on W1D1; 85 mg SC on W1D2, Weeks 2, 3 and 4; 340 mg SC, Q4W from Week 5 until end of study 30 kg to < 40 kg: 400 mg IV on W1D1; 170 mg SC on W1D2, Weeks 2, 3 and 4; 510 mg SC, Q4W from Week 5 until end of study 40 kg to < 100 kg: 1000 mg IV on W1D1; 340 mg SC W1D2, Weeks 2, 3 and 4; 680 mg SC, Q4W from Week 5 until end of study 100 kg: 1500 mg IV on W1D1; 340 mg SC W1D2, Weeks 2, 3 and 4; 1020 mg SC, Q4W from Week 5 until end of study.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Transfusion Avoidance (TA)	TA is defined as participants who are packed red blood cell (pRBC) transfusion-free and do not require transfusion per protocol-specified guidelines. 95% Confidence Interval (CI) for percentage of participants with TA was calculated using the Wilson's method with continuity correction. Participants who withdrew before Week 25 were deemed to have had a transfusion. Percentages are rounded off to the nearest single decimal.	Baseline to Week 25
Percentage of Participants With Hemolysis Control Measured by LDH	A Generalized Estimating Equation (GEE) was used to estimate the population-average percentage of the participants with hemolysis control (measured by LDH ≤1.5 x upper limit of normal (ULN)) from Week 5 to Week 25 taking account of the intra-patient and inter-patient correlation between LDH control statuses across visits. Percentages are rounded off to the nearest single decimal.	Week 5 to Week 25

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Breakthrough Hemolysis (BTH)	BTH 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 per deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2xULN after a prior LDH reduction to ≤1.5xULN from the start of study treatment. 95% CI for percentage of participants with BTH was calculated using the Wilson's method with continuity correction. Participants who withdrew before Week 25 were deemed to have experienced a BTH event. Percentages are rounded off to the nearest single decimal.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Body weight ≥ 40 kg at screening (pediatric participants with body weight < 40 kg)
Willingness and ability to comply with all study visits and procedures
Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry
LDH level ≥ 2x ULN at screening (as per local assessment)
Vaccination against Neisseria meningitidis serotypes A, C, W, and Y< 3 years prior to initiation of study treatment; or, if not previously done, vaccination administered no later than one week after the first drug administration
Women of childbearing potential: agreement to remain abstinent or use contraception during the treatment period and for 10.5 months after the final dose of crovalimab or for 3 months after the final dose of eculizumab (or longer if required by the local product label)

Exclusion Criteria:

Current or previous treatment with a complement inhibitor
History of allogeneic bone marrow transplantation
History of Neisseria meningitidis infection within 6 months prior to screening and up to first study drug administration
History of myelodysplastic syndrome with Revised International Prognostic Scoring System (IPSS-R) prognostic risk categories of intermediate, high and very high
Pregnant or breastfeeding, or intending to become pregnant during the study, within 10.5 months after the final dose of crovalimab, or 3 months after the final dose of eculizumab (or longer if required by the local product label)
Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within 5 half-lives of that investigational product, whichever is greater
Concurrent disease, treatment, procedure or surgery, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose any additional risk for the participant, or would, in the opinion of the Investigator, preclude the participant's safe participation in and completion of the study
Splenectomy < 6 months before screening
Positive for Active Hepatitis B and C infection (HBV/HCV)
History of or ongoing cryoglobulinemia at screening

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Organizacion Medica de Investigacion (OMI)		Ciudad Autonoma Buenos Aires		C1015ABO	Argentina
XCEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
42287326	Derived	Tong H, Lin Z, Yang C, Wang X, Sun J, Xia L, Shi J, Shi D, Zhang Z, Appius A, He G. Efficacy and safety of crovalimab versus eculizumab in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria: Chinese subgroup analysis of the phase 3 COMMODORE 2 study. Ann Hematol. 2026 Jun 13. doi: 10.1007/s00277-026-07129-3. Online ahead of print.
40978458

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A: Crovalimab	Crovalimab was administered at an initial loading dose of 1000 milligram (mg) (for participants with body weight between 40 and 100 kilogram (kg)) or 1500 mg (for participants with body weight >=100kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) once every 4 weeks (Q4W) from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 15, 2023	Sep 15, 2025

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

FG000135 subjects
FG00169 subjects
FG0026 subjects

All Participant Population includes all participant enrolled to the originally assigned treatment arms (Arms A, B and C).

Arm/Group Information

ID	Title	Description
BG000	Arm A: Crovalimab	Crovalimab was administered at an initial loading dose of 1000 milligram (mg) (for participants with body weight between 40 and 100 kilogram (kg)) or 1500 mg (for participants with body weight >=100kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) once every 4 weeks (Q4W) from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.
BG001	Arm B: Eculizumab	Participants received loading doses of eculizumab 600 mg IV on Days 1, 8, 15, and 22, followed by maintenance doses of 900 mg IV on Day 29 and every 2 weeks (Q2W) thereafter up to Week 24 in the primary treatment period. Participants who switched to crovalimab received crovalimab as an IV loading dose of 1000 mg (if body weight was between 40 kg to <100 kg) or 1500 mg (if body weight was >=100kg) on Week 25 Day 1, 340 mg SC on Week 25 Day 2, then 340 mg SC QW on Weeks 26, 27, 28, followed by crovalimab maintenance dose of 680 mg SC (if body weight was between 40 kg to <100 kg) or 1020 mg SC (if body weight was >=100kg) on Week 29 and Q4W thereafter up to a maximum of 5 years in the extension treatment period.
BG002	Arm C: Crovalimab	Pediatric participants received initial loading dose of 1000 mg (for participants with body weight between 40 and 100 kg) or 1500 mg (for participants with body weight >=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) Q4W from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.
BG003	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 BG0012 BG0026 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00058 BG00134 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00018 BG0016 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 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

Percentage of Participants With Transfusion Avoidance (TA)

TA is defined as participants who are packed red blood cell (pRBC) transfusion-free and do not require transfusion per protocol-specified guidelines. 95% Confidence Interval (CI) for percentage of participants with TA was calculated using the Wilson's method with continuity correction. Participants who withdrew before Week 25 were deemed to have had a transfusion. Percentages are rounded off to the nearest single decimal.

Primary Analysis Population (PAP) included all randomized participants in Arms A and B who received at least one dose of the originally assigned treatment and having at least one valid lactate dehydrogenase (LDH) level assessment by the central laboratory after the first IV infusion by planned treatment.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline to Week 25

ID	Title	Description
OG000	Arm A: Crovalimab	Crovalimab was administered at an initial loading dose of 1000 milligram (mg) (for participants with body weight between 40 and 100 kilogram (kg)) or 1500 mg (for participants with body weight >=100kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) once every 4 weeks (Q4W) from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.
OG001	Arm B: Eculizumab	Participants received loading doses of eculizumab 600 mg IV on Days 1, 8, 15, and 22, followed by maintenance doses of 900 mg IV on Day 29 and every 2 weeks (Q2W) thereafter up to Week 24 in the primary treatment period. Participants who switched to crovalimab received crovalimab as an IV loading dose of 1000 mg (if body weight was between 40 kg to <100 kg) or 1500 mg (if body weight was >=100kg) on Week 25 Day 1, 340 mg SC on Week 25 Day 2, then 340 mg SC QW on Weeks 26, 27, 28, followed by crovalimab maintenance dose of 680 mg SC (if body weight was between 40 kg to <100 kg) or 1020 mg SC (if body weight was >=100kg) on Week 29 and Q4W thereafter up to a maximum of 5 years in the extension treatment period.

Units	Counts
Participants	OG000134 OG00169

Title

Denominators

Categories

Title	Measurements
	OG00065.7(56.91 to 73.52) OG00168.1(55.67 to 78.53)

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						Weighted Difference in Proportion	-2.8			2-Sided	95	-15.67	11.14			95% CI for the difference in proportions of participants with TA is calculated by Stratified Newcombe CI method.		Non-Inferiority	Non-inferiority is met when the lower limit of the 95% CI is greater than -20%.

Primary

Percentage of Participants With Hemolysis Control Measured by LDH

A Generalized Estimating Equation (GEE) was used to estimate the population-average percentage of the participants with hemolysis control (measured by LDH ≤1.5 x upper limit of normal (ULN)) from Week 5 to Week 25 taking account of the intra-patient and inter-patient correlation between LDH control statuses across visits. Percentages are rounded off to the nearest single decimal.

Posted

Number

95% Confidence Interval

percentage of participants

Week 5 to Week 25

ID	Title	Description
OG000	Arm A: Crovalimab	Crovalimab was administered at an initial loading dose of 1000 milligram (mg) (for participants with body weight between 40 and 100 kilogram (kg)) or 1500 mg (for participants with body weight >=100kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) once every 4 weeks (Q4W) from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.

Secondary

Percentage of Participants With Breakthrough Hemolysis (BTH)

BTH 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 per deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2xULN after a prior LDH reduction to ≤1.5xULN from the start of study treatment. 95% CI for percentage of participants with BTH was calculated using the Wilson's method with continuity correction. Participants who withdrew before Week 25 were deemed to have experienced a BTH event. Percentages are rounded off to the nearest single decimal.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline to Week 25

ID	Title	Description
OG000	Arm A: Crovalimab	Crovalimab was administered at an initial loading dose of 1000 milligram (mg) (for participants with body weight between 40 and 100 kilogram (kg)) or 1500 mg (for participants with body weight >=100kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) once every 4 weeks (Q4W) from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.

Secondary

Percentage of Participants With Stabilization of Hemoglobin

Stabilized hemoglobin is defined as avoidance of a >= 2 g/dL decrease in hemoglobin level from baseline, in the absence of transfusion. 95% CI for percentage of participants with stabilized hemoglobin was calculated using the Wilson's method with continuity correction. Participants who withdrew before Week 25 were deemed to not have had hemoglobin stabilization. Percentages are rounded off to the nearest single decimal.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline to Week 25

ID	Title	Description
OG000	Arm A: Crovalimab	Crovalimab was administered at an initial loading dose of 1000 milligram (mg) (for participants with body weight between 40 and 100 kilogram (kg)) or 1500 mg (for participants with body weight >=100kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) once every 4 weeks (Q4W) from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.

Secondary

Change From Baseline in Fatigue Assessed by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale

Fatigue was assessed using FACIT-F scale. FACIT-F is a self-assessment questionnaire with a 7-day recall period and 13 items evaluating fatigue and its impact on daily life activities. Items are scored on a response scale that ranges from 0 ("not at all") to 4 ("very much so"). Relevant items are reverse scored, and all the items are summed to create a total score range from 0 to 52, with 0 being the worst possible score and 52 being the best possible score. A higher score indicates low fatigue severity. A positive mean change indicates improvement. FACIT-F was assessed in adult participants only.

PAP included all randomized participants in Arms A and B who received at least one dose of the originally assigned treatment and having at least one valid LDH level assessment by the central laboratory after the first IV infusion by planned treatment. Overall number of participants analyzed is the number of participants ≥18 years with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

Posted

Mean

Standard Error

score on scale

Baseline to Week 25

ID	Title	Description
OG000	Arm A: Crovalimab	Crovalimab was administered at an initial loading dose of 1000 milligram (mg) (for participants with body weight between 40 and 100 kilogram (kg)) or 1500 mg (for participants with body weight >=100kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) once every 4 weeks (Q4W) from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.

Secondary

Percentage of Participants With Adverse Events (AEs)

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs are reported based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.

Not Posted

Sep 2028

Up to 6 years

Participants

Secondary

Percentage of Participants With Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (Including Meningococcal Meningitis)

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Injection-site reactions or infusion-related reaction are AEs related to the injection site that occur during or within 24 hours after study drug administration that are judged to be related to the study drug injection.

Not Posted

Sep 2028

Up to 6 years

Participants

Secondary

Percentage of Participants With AEs Leading to Study Drug Discontinuation

Not Posted

Sep 2028

Up to 6 years

Participants

Secondary

Percentage of Participants With Clinical Manifestations of Drug-Target-Drug Complex (DTDC) Formation Amongst Participants Who Switched to Crovalimab Treatment From Eculizumab Treatment

Not Posted

Sep 2028

Up to 6 years

Participants

Secondary

Serum Concentrations of Crovalimab And Eculizumab Over Time

Not Posted

Sep 2028

Up to 6 years

Participants

Secondary

Percentage of Participants With Anti-Crovalimab Antibodies

Not Posted

Sep 2028

Up to 6 years

Participants

Secondary

Change in Pharmacodynamic (PD) Biomarkers Including Complement Activity (CH50) Over Time

Not Posted

Sep 2028

Up to 6 years

Participants

Secondary

Change Over Time in Free C5 Concentration in Crovalimab-Treated Participants

Not Posted

Sep 2028

Up to 6 years

Participants

Secondary

Observed Value in Reticulocyte Count (Count/Milliliters [mL])

Not Posted

Sep 2028

Up to 6 years

Participants

Secondary

Observed Value in Haptoglobin (Milligrams Per Deciliter [mg/dL])

Not Posted

Sep 2028

Up to 6 years

Participants

Secondary

Change From Baseline in Absolute Reticulocyte Count

Randomized Safety Population includes all randomized participants who have received at least one dose of study treatment. Includes only participants from Arms A and B. Overall number of participants analyzed is the number of participants ≥18 years with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

Posted

Mean

Standard Deviation

10^9 cells/liter (L)

Baseline, Day 1 Week 1, Week 2, 3, 4, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23 and 25

ID	Title	Description
OG000	Arm A: Crovalimab	Crovalimab was administered at an initial loading dose of 1000 milligram (mg) (for participants with body weight between 40 and 100 kilogram (kg)) or 1500 mg (for participants with body weight >=100kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) once every 4 weeks (Q4W) from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.
OG001	Arm B: Eculizumab	Participants received loading doses of eculizumab 600 mg IV on Days 1, 8, 15, and 22, followed by maintenance doses of 900 mg IV on Day 29 and every 2 weeks (Q2W) thereafter up to Week 24 in the primary treatment period. Participants who switched to crovalimab received crovalimab as an IV loading dose of 1000 mg (if body weight was between 40 kg to <100 kg) or 1500 mg (if body weight was >=100kg) on Week 25 Day 1, 340 mg SC on Week 25 Day 2, then 340 mg SC QW on Weeks 26, 27, 28, followed by crovalimab maintenance dose of 680 mg SC (if body weight was between 40 kg to <100 kg) or 1020 mg SC (if body weight was >=100kg) on Week 29 and Q4W thereafter up to a maximum of 5 years in the extension treatment period.

Secondary

Change From Baseline in Free Hemoglobin

Posted

Mean

Standard Deviation

milligram per litre (mg)/L

Baseline, Week 2, 3, 4, 5, 9, 13, 17, 21, and 25

ID	Title	Description
OG000	Arm A: Crovalimab	Crovalimab was administered at an initial loading dose of 1000 milligram (mg) (for participants with body weight between 40 and 100 kilogram (kg)) or 1500 mg (for participants with body weight >=100kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) once every 4 weeks (Q4W) from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.
OG001	Arm B: Eculizumab	Participants received loading doses of eculizumab 600 mg IV on Days 1, 8, 15, and 22, followed by maintenance doses of 900 mg IV on Day 29 and every 2 weeks (Q2W) thereafter up to Week 24 in the primary treatment period. Participants who switched to crovalimab received crovalimab as an IV loading dose of 1000 mg (if body weight was between 40 kg to <100 kg) or 1500 mg (if body weight was >=100kg) on Week 25 Day 1, 340 mg SC on Week 25 Day 2, then 340 mg SC QW on Weeks 26, 27, 28, followed by crovalimab maintenance dose of 680 mg SC (if body weight was between 40 kg to <100 kg) or 1020 mg SC (if body weight was >=100kg) on Week 29 and Q4W thereafter up to a maximum of 5 years in the extension treatment period.

Secondary

Change From Baseline in Haptoglobin

Posted

Mean

Standard Deviation

gram (g)/L

Baseline, Week 2, 3, 4, 5, 9, 13, 15, 17, 21, and 25

ID	Title	Description
OG000	Arm A: Crovalimab	Crovalimab was administered at an initial loading dose of 1000 milligram (mg) (for participants with body weight between 40 and 100 kilogram (kg)) or 1500 mg (for participants with body weight >=100kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) once every 4 weeks (Q4W) from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.
OG001	Arm B: Eculizumab	Participants received loading doses of eculizumab 600 mg IV on Days 1, 8, 15, and 22, followed by maintenance doses of 900 mg IV on Day 29 and every 2 weeks (Q2W) thereafter up to Week 24 in the primary treatment period. Participants who switched to crovalimab received crovalimab as an IV loading dose of 1000 mg (if body weight was between 40 kg to <100 kg) or 1500 mg (if body weight was >=100kg) on Week 25 Day 1, 340 mg SC on Week 25 Day 2, then 340 mg SC QW on Weeks 26, 27, 28, followed by crovalimab maintenance dose of 680 mg SC (if body weight was between 40 kg to <100 kg) or 1020 mg SC (if body weight was >=100kg) on Week 29 and Q4W thereafter up to a maximum of 5 years in the extension treatment period.

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	Arm A: Crovalimab	Crovalimab was administered at an initial loading dose of 1000 milligram (mg) (for participants with body weight between 40 and 100 kilogram (kg)) or 1500 mg (for participants with body weight >=100kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) once every 4 weeks (Q4W) from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.	2	135	22	135	102	135
EG001	Arm B: Eculizumab	Participants received loading doses of eculizumab 600 mg IV on Days 1, 8, 15, and 22, followed by maintenance doses of 900 mg IV on Day 29 and every 2 weeks (Q2W) thereafter up to Week 24 in the primary treatment period. Participants who switched to crovalimab received crovalimab as an IV loading dose of 1000 mg (if body weight was between 40 kg to <100 kg) or 1500 mg (if body weight was >=100kg) on Week 25 Day 1, 340 mg SC on Week 25 Day 2, then 340 mg SC QW on Weeks 26, 27, 28, followed by crovalimab maintenance dose of 680 mg SC (if body weight was between 40 kg to <100 kg) or 1020 mg SC (if body weight was >=100kg) on Week 29 and Q4W thereafter up to a maximum of 5 years in the extension treatment period.	1	69	14	69	55	69
EG002	Arm C: Crovalimab	Pediatric participants received initial loading dose of 1000 mg (for participants with body weight between 40 and 100 kg) or 1500 mg (for participants with body weight >=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight >=100kg) Q4W from Week 5 until 24 weeks in primary treatment period. After Week 24, participants continued to receive maintenance dose of crovalimab up to a maximum of 5 years in the extension treatment period.	0	6	0	6	5	6

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Aplastic anaemia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0004 events2 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Breakthrough haemolysis	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Cardiac failure	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Coronary artery disease	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Myocardial infarction	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Small intestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Pyrexia	General disorders	MedDRA 25.1	Systematic Assessment	EG0002 events1 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
COVID-19	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Central nervous system infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Dengue fever	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Gastroenteritis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Influenza	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Pneumonia	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0004 events4 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Pyelonephritis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Sepsis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Septic shock	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Tuberculosis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Urinary tract infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Limb traumatic amputation	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Mantle cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0012 events1 affected69 at risk EG0020 events0 affected6 at risk
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Demyelinating polyneuropathy	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Seizure	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Affective disorder	Psychiatric disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Paroxysmal nocturnal haemoglobinuria	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0011 events1 affected69 at risk EG0020 events0 affected6 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0003 events2 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Respiratory tract haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Henoch-Schonlein purpura	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk
Hypovolaemic shock	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected135 at risk EG0010 events0 affected69 at risk EG0020 events0 affected6 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Aphthous ulcer	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG0010 events0 affected69 at risk EG0021 events1 affected6 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG00012 events11 affected135 at risk EG0012 events2 affected69 at risk EG0020 events0 affected6 at risk
Fatigue	General disorders	MedDRA 25.1	Systematic Assessment	EG0004 events4 affected135 at risk EG0013 events3 affected69 at risk EG0021 events1 affected6 at risk
Pyrexia	General disorders	MedDRA 25.1	Systematic Assessment	EG00018 events15 affected135 at risk EG00111 events8 affected69 at risk EG0021 events1 affected6 at risk
Type III immune complex mediated reaction	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected135 at risk EG00112 events11 affected69 at risk EG0020 events0 affected6 at risk
COVID-19	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG00028 events28 affected135 at risk EG0019 events9 affected69 at risk EG0020 events0 affected6 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG00021 events17 affected135 at risk EG00114 events11 affected69 at risk EG0020 events0 affected6 at risk
Urinary tract infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0008 events5 affected135 at risk EG0015 events5 affected69 at risk EG0021 events1 affected6 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected135 at risk EG0012 events1 affected69 at risk EG0021 events1 affected6 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG00021 events20 affected135 at risk EG00112 events10 affected69 at risk EG0020 events0 affected6 at risk
Injection related reaction	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0007 events7 affected135 at risk EG0014 events4 affected69 at risk EG0020 events0 affected6 at risk
Alanine aminotransferase increased	Investigations	MedDRA 25.1	Systematic Assessment	EG0004 events4 affected135 at risk EG0014 events4 affected69 at risk EG0020 events0 affected6 at risk
Neutrophil count decreased	Investigations	MedDRA 25.1	Systematic Assessment	EG00045 events18 affected135 at risk EG00115 events8 affected69 at risk EG0020 events0 affected6 at risk
White blood cell count decreased	Investigations	MedDRA 25.1	Systematic Assessment	EG00046 events17 affected135 at risk EG00129 events10 affected69 at risk EG0020 events0 affected6 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG00017 events11 affected135 at risk EG00117 events7 affected69 at risk EG0023 events2 affected6 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG00012 events8 affected135 at risk EG00116 events7 affected69 at risk EG0021 events1 affected6 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG00034 events15 affected135 at risk EG00125 events9 affected69 at risk EG0021 events1 affected6 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0008 events3 affected135 at risk EG0012 events1 affected69 at risk EG0024 events1 affected6 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0005 events5 affected135 at risk EG0014 events4 affected69 at risk EG0020 events0 affected6 at risk
Dizziness	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0004 events3 affected135 at risk EG00113 events4 affected69 at risk EG0020 events0 affected6 at risk
Headache	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG00017 events13 affected135 at risk EG0019 events6 affected69 at risk EG0021 events1 affected6 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0008 events7 affected135 at risk EG0012 events2 affected69 at risk EG0020 events0 affected6 at risk

First MCP Posted Date

ID	Term
D006457	Hemoglobinuria, Paroxysmal

ID	Term
C481642	eculizumab

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