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

NCT04432584 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: BO421612020-000597-262023-506526-37-00
• Study Type: interventional
• Target: 190
• Locations: 23 countries
• Sites: 69

Brief Summary

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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (9)

• 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

Study Arms (3)

Arm A (Crovalimab)

EXPERIMENTAL

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

Arm B (Eculizumab)

ACTIVE COMPARATOR

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

Arm C (Crovalimab) (Exploratory)

EXPERIMENTAL

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

Interventions

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.

Arm A (Crovalimab); Arm C (Crovalimab) (Exploratory)

Eculizumab DRUG

Eculizumab will be administered at a dose of 900 mg Q2W, as per the dosing schedule described above.

Arm B (Eculizumab)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Chugai Pharmaceutical: collaborator

Study Sites (80)

Carolinas Healthcare System

Charlotte, North Carolina, 28204, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

AZ Delta Campus Westlaan

Roeselare, 8800, Belgium

Location

CHU UCL Namur / site Godinne

Yvoir, 5530, Belgium

Location

Chronos Pesquisa Clinica

Taguatinga, Federal District, 72145-450, Brazil

Location

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

Hospital de Clínicas de Porto Alegre X

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Instituto Joinvilense de Hematologia E Oncologia

Joinville, Santa Catarina, 89201-260, Brazil

Location

Hospital das Clínicas FMRP-USP

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

*X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia

Santo André, São Paulo, 09060-870, Brazil

Location

Hospital Sírio-Libanês

São Paulo, São Paulo, 01308-050, Brazil

Location

Hospital Paulistano

São Paulo, São Paulo, 01321-000, Brazil

Location

Beneficencia Portuguesa de Sao Paulo

São Paulo, 01321-00, Brazil

Location

Ustav hematologie a krevni transfuze

Prague, 128 00, Czechia

Location

North Estonia Medical Centre Foundation

Tallinn, 13419, Estonia

Location

Hopital Claude Huriez - CHU Lille

Lille, 59037, France

Location

Universitaetsklinikum Aachen AOeR

Aachen, 52074, Germany

Location

ELBLANDKLINIKUM Riesa

Riesa, 01589, Germany

Location

General Hospital of Athens LAIKO

Athens, 115 27, Greece

Location

Attikon University General Hospital

Athens, 124 62, Greece

Location

Prince of Wales Hospital

Hong Kong, 999077, Hong Kong

Location

Semmelweis Egyetem

Budapest, 1088, Hungary

Location

St James's Hospital

Dublin, D08NYH1, Ireland

Location

Azienda Unita Sanitaria Locale- Ravenna

Ravenna, Emilia-Romagna, 48121, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, 00168, Italy

Location

Fondazione IRCCS CA? Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

Location

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont, 10126, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, 50134, Italy

Location

Fujita Health University Hospital

Aichi, 470-1192, Japan

Location

Kobe University Hospital

Hyōgo, 650-0017, Japan

Location

Tokushukai Takasago Seibu Hospital

Hyōgo, 676-0812, Japan

Location

Ishikawa Prefectural Central Hospital

Ishikawa, 920-8530, Japan

Location

Tokai University Hospital

Kanagawa, 259-1193, Japan

Location

Mie University Hospital

Mie, 514-8507, Japan

Location

Japanese Red Cross Society Suwa Hospital

Nagano, 392-8510, Japan

Location

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

Location

Sasebo City General Hospital

Nagasaki, 857-8511, Japan

Location

National Hospital Organization Okayama Medical Center

Okayama, 701-1192, Japan

Location

The University of Osaka Hospital

Osaka, 565-0871, Japan

Location

Iwate Prefectural Isawa Hospital

Ōshū, 023-0864, Japan

Location

NTT Medical Center Tokyo

Tokyo, 141-8625, Japan

Location

Tokyo Medical University Hospital

Tokyo, 160-0023, Japan

Location

Toyama Prefectual Central Hospital

Toyama, 930-8550, Japan

Location

Amsterdam UMC, Locatie AMC

Amsterdam, 1105 AZ, Netherlands

Location

Szpital Uniwersytecki nr2 im. dr J. Biziela

Bydgoszcz, 85-168, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 1

Lublin, 20-081, Poland

Location

Pratia Poznan

Skórzewo, 60-185, Poland

Location

MTZ Clinical Research Powered by Pratia

Warsaw, 02-172, Poland

Location

Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro

Aveiro, 3814-501, Portugal

Location

Centro Hospitalar do Porto - Hospital de Santo António

Porto, 4099-001, Portugal

Location

King Faisal Specialist Hospital & Research Center

Riyadh, 11211, Saudi Arabia

Location

National University Hospital

Singapore, 117599, Singapore

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Ulsan University Hospital

Ulsan, 44033, South Korea

Location

ICO Badalona - Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Complejo Hospitalario Universitario de Santiago.

Santiago de Compostela, LA Coruna, 15706, Spain

Location

Hospital U. Central de Asturias

Asturias, Principality of Asturias, 33011, Spain

Location

Hospital de Basurto

Bilbao, Vizcaya, 48013, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28009, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitario de Toledo

Toledo, 45007, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Akademiska Sjukhuset

Uppsala, 751 85, Sweden

Location

Changhua Christian Hospital

Chang-hua, 500, Taiwan

Location

Hualien Tzu Chi Hospital

Hualien City, DUMMY_VALUE, Taiwan

Location

National Taiwan Universtiy Hospital

Taipei, 100, Taiwan

Location

Hacettepe University Medical Faculty; Neurology

Ankara, 06100, Turkey (Türkiye)

Location

Gaziantep University Medical Faculty Sahinbey Educational Research Hospital; Hematology

Gaziantep, 27310, Turkey (Türkiye)

Location

Istanbul University Istanbul Medical Faculty; Neurology

Istanbul, 34093, Turkey (Türkiye)

Location

Marmara University Pendik Training and Research Hospital, Hematology Department

Istanbul, 34300, Turkey (Türkiye)

Location

Ege University Medical Faculty; Hematology

Izmir, 35040, Turkey (Türkiye)

Location

Ondokuz Mayis Univ. Med. Fac.

Samsun, 55139, Turkey (Türkiye)

Location

King'S College Hospital

London, SE5 9RS, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 40978458 DERIVED

• 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.

  PMID: 39535306 DERIVED

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 16, 2020
• Study Start: September 30, 2020
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

SE (1); GR (2); HU (1); PL (5); TW (3); TU (6); ES (1); BR (9); IT (5); DE (2); BE (3); IE (1); PT (2); HK (1); FR (1); JP (15); NL (1); SA (1); SG (1); US (2); KR (4); GB (1); CZ (1)