A Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors (COMMODORE 2)

A Phase III, Randomized, Open-label, Active-controlled, Multicenter Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors

A study designed to evaluate the non-inferiority of crovalimab compared with eculizumab in participants with PNH who have not been previously treated with complement inhibitor therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Drug: Eculizumab; Drug: Crovalimab

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina, C1015ABO
    • Organizacion Medica de Investigacion (OMI)
• Brazil
  • São Paulo, Brazil, 01321-00
    • Beneficencia Portuguesa de Sao Paulo
  • São Paulo
    • Santo André, São Paulo, Brazil, 09060-870
      • *X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
  • Guangzhou, China, 510515
    • Nanfang Hospital, Southern Medical University
  • Hangzhou, China, 310003
    • The First Affiliated Hospital, Zhejiang University
  • Nanjing, China, 210029
    • Jiangsu Province Hospital
  • Nantong, China, 226001
    • Affiliated Hospital of Nantong University
  • Shanghai, China, 200040
    • Huashan Hospital, Fudan University
  • Wuhan, China, 430022
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
• France
  • Lille, France, 59037
    • Hopital Claude Huriez - CHU Lille
  • Rhone
    • Pierre-Bnite, Rhone, France, 69310
      • Centre Hospitalier Lyon Sud
• Germany
  • Essen, Germany, 45147
    • Universitaetsklinkm
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm
• Greece
  • Thessaloniki, Greece, 570 10
    • General Hospital of Thessaloniki G. Papanikolaou
• Japan
  • Hokkaido, Japan, 060-8543
    • Sapporo Medical University Hospital
  • Ibaraki, Japan, 305-8576
    • University of Tsukuba Hospital
  • Tokyo, Japan, 160-0023
    • Tokyo Medical University Hospital
  • Tokyo, Japan, 141-8625
    • Ntt Medical Center Tokyo
• Lithuania
  • Vilnius, Lithuania, LT-08661
    • Vilnius University Hospital Santariskiu Clinics, Public Institution
• Malaysia
  • Perak
    • Ipoh, Perak, Malaysia, 30450
      • Hospital Raja Permaisuri Bainun
  • Selangor
    • Ampang, Selangor, Malaysia, 68000
      • Hospital Ampang
• Mexico
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 14080
      • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64718
      • Global Trial Research Center S.A. de C.V.
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC, locatie AMC
• Philippines
  • Lipa City, Philippines, 4217
    • Mary Mediatrix Medical Center
  • Manila, Philippines, 1000
    • Philippine General Hospital
  • Quezon, Philippines, 1102
    • St Lukes Medical Center
• Poland
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr2 im. dr J. Biziela
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny nr 1
  • Skórzewo, Poland, 60-185
    • Pratia Poznan
  • Warsaw, Poland, 02-172
    • MTZ Clinical Research powered by Pratia
• Portugal
  • Aveiro, Portugal, 3810-501
    • Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro
  • Lisbon, Portugal, 1099-023
    • Instituto Portugues Oncologia de Lisboa Francisco Gentil EPE
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto - Hospital de Santo António
• Romania
  • Bucharest, Romania, 050098
    • Spitalul Universitar de Urgenta Bucuresti
  • Craiova, Romania, 200143
    • Spitalul Clinic Municipal Filantropia Craiova
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 169856
    • Singapore General Hospital
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Cáceres, Spain, 10003
    • Hospital San Pedro de Alcantara
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain, 28040
    • Hospital Universitario Clinico San Carlos
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Albacete
    • Bilbao, Albacete, Spain, 48013
      • Hospital de Basurto
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Ico Badalona - Hospital Universitari Germans Trias I Pujol
  • LAS Palmas
    • Las Palmas de Gran Canaria, LAS Palmas, Spain, 35019
      • Hospital Universitario de Gran Canaria Dr. Negrin
• Taiwan
  • Kaohisung, Taiwan, DUMMY_VALUE
    • Chang Gung Medical Foundation - Kaohsiung
  • Taipei, Taiwan, 100
    • National Taiwan Universtiy Hospital
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital
• Turkey (Türkiye)
  • Samsun, Turkey (Türkiye), 55139
    • Ondokuz Mayis Univ. Med. Fac.
• Ukraine
  • KIEV Governorate
    • Kyiv, KIEV Governorate, Ukraine, 02091
      • Medical Center Ok!Clinic+
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St James University Hospital
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm B (Eculizumab); 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: Eculizumab; Eculizumab will be administered as specified in the respective arm.; Drug: Crovalimab; 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.
Experimental: Arm A (Crovalimab); 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; 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.
Experimental: Arm C (Crovalimab) (Exploratory); 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.	Drug: Crovalimab; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 Outcome Measures

Outcome Measure	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.	Baseline to Week 25
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.	Baseline to Week 25
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.	Baseline to Week 25
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.	Up to 6 years
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.	Up to 6 years
Percentage of Participants With AEs Leading to Study Drug Discontinuation	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.	Up to 6 years
Percentage of Participants With Clinical Manifestations of Drug-Target-Drug Complex (DTDC) Formation Amongst Participants Who Switched to Crovalimab Treatment From Eculizumab Treatment		Up to 6 years
Serum Concentrations of Crovalimab And Eculizumab Over Time		Up to 6 years
Percentage of Participants With Anti-Crovalimab Antibodies		Up to 6 years
Change in Pharmacodynamic (PD) Biomarkers Including Complement Activity (CH50) Over Time		Up to 6 years
Change Over Time in Free C5 Concentration in Crovalimab-Treated Participants		Up to 6 years
Observed Value in Reticulocyte Count (Count/Milliliters [mL])		Up to 6 years
Observed Value in Haptoglobin (Milligrams Per Deciliter [mg/dL])		Up to 6 years
Change From Baseline in Absolute Reticulocyte Count		Baseline, Day 1 Week 1, Week 2, 3, 4, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23 and 25
Change From Baseline in Free Hemoglobin		Baseline, Week 2, 3, 4, 5, 9, 13, 17, 21, and 25
Change From Baseline in Haptoglobin		Baseline, Week 2, 3, 4, 5, 9, 13, 15, 17, 21, and 25

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Chugai Pharmaceutical
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Roth A, Fu R, He G, Alzahrani H, Chou SC, Hicheri Y, Kazmierczak M, Recova VL, Uchiyama M, Vladareanu AM, Beveridge L, Buatois S, Buri M, Compagno N, Shi D, Balachandran N, Sreckovic S, Scheinberg P. Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Haemoglobinuria (PNH): Pooled Results From the Phase 3 COMMODORE Studies. Eur J Haematol. 2025 Feb;114(2):373-382. doi: 10.1111/ejh.14339. Epub 2024 Nov 13.
• Kulasekararaj AG, Nishimura JI, Roth A, Beveridge L, Buatois S, Buri M, Compagno N, Luder Y, Sreckovic S, Scheinberg P. Managing transient immune complex reactions in patients with paroxysmal nocturnal hemoglobinuria: clinical observations from the COMMODORE 1 and 2 studies. Ther Adv Hematol. 2025 Sep 17;16:20406207251359246. doi: 10.1177/20406207251359246. eCollection 2025.

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2020
• Primary Completion (Actual): November 16, 2022
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: June 12, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic; Anemia; Myelodysplastic Syndromes; Hemic and Lymphatic Diseases; Hemoglobinuria, Paroxysmal; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; eculizumab
• Other Study ID Numbers: BO42162; 2019-004931-21 (EudraCT Number); 2023-506498-36-00 (Ctis: EU Clinical Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No