A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors (COMMODORE 1)

A Phase III, Randomized, Open-label, Active-controlled, Multicenter Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamic and Efficacy of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors

A study designed to evaluate the safety of crovalimab with eculizumab in participants with PNH currently treated with complement inhibitors. This study will enroll approximately 190 participants.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 190
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Roeselare, Belgium, 8800
    • AZ Delta Campus Westlaan
  • Yvoir, Belgium, 5530
    • CHU UCL Namur / site Godinne
• Brazil
  • São Paulo, Brazil, 01321-00
    • Beneficencia Portuguesa de Sao Paulo
  • Federal District
    • Taguatinga, Federal District, Brazil, 72145-450
      • Chronos Pesquisa Clinica
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90020-090
      • Santa Casa de Misericordia de Porto Alegre
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clínicas de Porto Alegre X
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil, 89201-260
      • Instituto Joinvilense de Hematologia E Oncologia
  • São Paulo
    • Ribeirão Preto, São Paulo, Brazil, 14048-900
      • Hospital das Clínicas FMRP-USP
    • Santo André, São Paulo, Brazil, 09060-870
      • *X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
    • São Paulo, São Paulo, Brazil, 01308-050
      • Hospital Sirio-Libanes
    • São Paulo, São Paulo, Brazil, 01321-000
      • Hospital Paulistano
• Czechia
  • Prague, Czechia, 128 00
    • Ustav hematologie a krevni transfuze
• Estonia
  • Tallinn, Estonia, 13419
    • North Estonia Medical Centre Foundation
• France
  • Lille, France, 59037
    • Hopital Claude Huriez - CHU Lille
• Germany
  • Aachen, Germany, 52074
    • Universitaetsklinikum Aachen AOeR
  • Riesa, Germany, 01589
    • Elblandklinikum Riesa
• Greece
  • Athens, Greece, 124 62
    • Attikon University General Hospital
  • Athens, Greece, 115 27
    • General Hospital of Athens Laiko
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Prince of Wales Hospital
• Hungary
  • Budapest, Hungary, 1088
    • Semmelweis Egyetem
• Ireland
  • Dublin, Ireland, D08NYH1
    • St James's Hospital
• Italy
  • Emilia-Romagna
    • Ravenna, Emilia-Romagna, Italy, 48121
      • Azienda Unita Sanitaria Locale- Ravenna
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Lombardy
    • Milan, Lombardy, Italy, 20122
      • Fondazione IRCCS CA? Granda Ospedale Maggiore Policlinico
  • Piedmont
    • Turin, Piedmont, Italy, 10126
      • Azienda Ospedaliera Città della Salute e della Scienza di Torino
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Azienda Ospedaliera Universitaria Careggi
• Japan
  • Aichi, Japan, 470-1192
    • Fujita Health University Hospital
  • Hyōgo, Japan, 650-0017
    • Kobe University Hospital
  • Hyōgo, Japan, 676-0812
    • Tokushukai Takasago Seibu Hospital
  • Ishikawa, Japan, 920-8530
    • Ishikawa Prefectural Central Hospital
  • Kanagawa, Japan, 259-1193
    • Tokai University Hospital
  • Mie, Japan, 514-8507
    • Mie University Hospital
  • Nagano, Japan, 392-8510
    • Japanese Red Cross Society Suwa Hospital
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Nagasaki, Japan, 857-8511
    • Sasebo City General Hospital
  • Okayama, Japan, 701-1192
    • National Hospital Organization Okayama Medical Center
  • Osaka, Japan, 565-0871
    • The University of Osaka Hospital
  • Tokyo, Japan, 160-0023
    • Tokyo Medical University Hospital
  • Tokyo, Japan, 141-8625
    • Ntt Medical Center Tokyo
  • Toyama, Japan, 930-8550
    • Toyama Prefectual Central Hospital
  • Ōshū, Japan, 023-0864
    • Iwate Prefectural Isawa Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC, locatie AMC
• Poland
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr2 im. dr J. Biziela
  • Gda?sk, Poland, 80-214
    • 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, 3814-501
    • Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto - Hospital de Santo António
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11211
    • King Faisal Specialist Hospital & Research Center
• Singapore
  • Singapore, Singapore, 117599
    • National University Hospital
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital
  • Ulsan, South Korea, 44033
    • Ulsan University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebrón
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Marañón
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Toledo, Spain, 45007
    • Hospital Universitario de Toledo
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Ico Badalona - Hospital Universitari Germans Trias I Pujol
  • LA Coruna
    • Santiago de Compostela, LA Coruna, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago.
  • Principality of Asturias
    • Asturias, Principality of Asturias, Spain, 33011
      • Hospital U. Central de Asturias
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital de Basurto
• Sweden
  • Uppsala, Sweden, 751 85
    • Akademiska sjukhuset
• Taiwan
  • Chang-hua, Taiwan, 500
    • Changhua Christian Hospital
  • Hualien City, Taiwan, DUMMY_VALUE
    • Hualien Tzu Chi Hospital
  • Taipei, Taiwan, 100
    • National Taiwan Universtiy Hospital
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06100
    • Hacettepe University Medical Faculty; Neurology
  • Gaziantep, Turkey (Türkiye), 27310
    • Gaziantep University Medical Faculty Sahinbey Educational Research Hospital; Hematology
  • Istanbul, Turkey (Türkiye), 34093
    • Istanbul University Istanbul Medical Faculty; Neurology
  • Istanbul, Turkey (Türkiye), 34300
    • Marmara University Pendik Training and Research Hospital, Hematology Department
  • Izmir, Turkey (Türkiye), 35040
    • Ege University Medical Faculty; Hematology
  • Samsun, Turkey (Türkiye), 55139
    • Ondokuz Mayis Univ. Med. Fac.
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Carolinas Healthcare System
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's 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)
• Treated with eculizumab or ravulizumab for PNH for at least 3 months prior to Day 1
• Lactate Dehydrogenase Levels ≤ 2x the upper limit of normal (ULN) at screening
• Willingness and ability to comply with all study visits and procedures
• Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry
• 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 (refrain from heterosexual intercourse) 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:

• History of allogeneic bone marrow transplantation
• 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 was greater: participants enrolled in an eculizumab or ravulizumab interventional study are eligible provided they fulfill eligibility (e.g., are willing and able to comply with the study assessments) and stop their participation in current trial before randomisation/enrolment
• Positive for Active Hepatitis B and C infection (HBV/HCV)
• 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
• 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
Experimental: Arm A (Crovalimab); Participants will receive a loading series of crovalimab comprised of an intravenous (IV) dose on Day 1, followed by weekly crovalimab subcutaneous (SC) doses for 4 weeks on Week 1 Day 2, then on Weeks 2, 3, and 4. Maintenance SC dosing will begin at Week 5 and will continue every 4 weeks (Q4W) thereafter for a total of 24 weeks of study treatment. 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.
Active Comparator: Arm B (Eculizumab); Participants will receive an approved maintenance dose of eculizumab starting on Day 1 and every 2 weeks (Q2W) thereafter for a total of 24 weeks of study treatment. After 24 weeks of study eculizumab treatment, participants will have the option to switch to crovalimab or to discontinue from the study after completion of 10 weeks of safety follow-up.	Drug: Eculizumab; Eculizumab will be administered at a dose of 900 mg Q2W, as per the dosing schedule described above.
Experimental: Arm C (Crovalimab) (Exploratory); Participants with a body weight ≥ 5 to <12 kilograms (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 Adverse Events (AEs) and by Severity	Severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5 (CTCAE v5).	Up to approximately 6 years
Percentage of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis)		Up to approximately 6 years
Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation		Up to approximately 6 years
Percentage of Participants With Clinical Manifestations of Drug-target-drug Complex (DTDC) Formation Amongst Those Participants Who Switched to Crovalimab Treatment From Eculizumab Treatment or Ravulizumab Treatment		Up to approximately 6 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum Concentrations of Crovalimab or Eculizumab Over Time	Up to approximately 6 years
Serum Concentrations of Ravulizumab at the Time of Crovalimab Initiation	Baseline
Percentage of Participants With Anti-crovalimab Antibodies	Up to approximately 6 years
Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time	Up to approximately 6 years
Change Over Time in Free C5 Concentration in Crovalimab-treated Participants	Up to approximately 6 years
Observed Value in Reticulocyte Count (count/milliliters [mL])	Up to approximately 6 years
Observed Value in Free Hemoglobin and Haptoglobin (milligrams per deciliter [mg/dL])	Up to approximately 6 years
Absolute Change From Baseline in Reticulocyte Count (count/mL)	Baseline up to Week 25
Absolute Change From Baseline in Free Hemoglobin and Haptoglobin (mg/dL)	Baseline up to Week 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): September 30, 2020
• Primary Completion (Estimated): September 30, 2027
• 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: BO42161; 2020-000597-26 (EudraCT Number); 2023-506526-37-00 (Ctis)

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