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

NCT ID: NCT04432584

Last Updated: 2025-10-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 190 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-30
• Study Completion Date: 2027-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Crovalimab

Intervention Type: 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 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.

Group Type: ACTIVE_COMPARATOR

Eculizumab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Crovalimab

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eculizumab

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chugai Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Carolinas Healthcare System

Charlotte, North Carolina, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

AZ Delta Campus Westlaan

Roeselare, , Belgium

CHU UCL Namur / site Godinne

Yvoir, , Belgium

Chronos Pesquisa Clinica

Taguatinga, Federal District, Brazil

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital de Clínicas de Porto Alegre X

Porto Alegre, Rio Grande do Sul, Brazil

Instituto Joinvilense de Hematologia E Oncologia

Joinville, Santa Catarina, Brazil

Hospital das Clínicas FMRP-USP

Ribeirão Preto, São Paulo, Brazil

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

Santo André, São Paulo, Brazil

Hospital Sírio-Libanês

São Paulo, São Paulo, Brazil

Hospital Paulistano

São Paulo, São Paulo, Brazil

Beneficencia Portuguesa de Sao Paulo

São Paulo, , Brazil

CISSS Chaudière-Appalaches

Lévis, Quebec, Canada

Ustav hematologie a krevni transfuze

Prague, , Czechia

North Estonia Medical Centre Foundation

Tallinn, , Estonia

Hopital Claude Huriez - CHU Lille

Lille, , France

Universitaetsklinikum Aachen AOeR

Aachen, , Germany

ELBLANDKLINIKUM Riesa

Riesa, , Germany

General Hospital of Athens LAIKO

Athens, , Greece

Attikon University General Hospital

Athens, , Greece

Prince of Wales Hospital

Hong Kong, , Hong Kong

Semmelweis Egyetem

Budapest, , Hungary

St James's Hospital

Dublin, , Ireland

Azienda Unita Sanitaria Locale- Ravenna

Ravenna, Emilia-Romagna, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, Italy

Fondazione IRCCS CA? Granda Ospedale Maggiore Policlinico

Milan, Lombardy, Italy

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, Italy

Fujita Health University Hospital

Aichi, , Japan

Kobe University Hospital

Hyōgo, , Japan

Tokushukai Takasago Seibu Hospital

Hyōgo, , Japan

Ishikawa Prefectural Central Hospital

Ishikawa, , Japan

Tokai University Hospital

Kanagawa, , Japan

Mie University Hospital

Mie, , Japan

Japanese Red Cross Society Suwa Hospital

Nagano, , Japan

Nagasaki University Hospital

Nagasaki, , Japan

Sasebo City General Hospital

Nagasaki, , Japan

National Hospital Organization Okayama Medical Center

Okayama, , Japan

The University of Osaka Hospital

Osaka, , Japan

Iwate Prefectural Isawa Hospital

Ōshū, , Japan

NTT Medical Center Tokyo

Tokyo, , Japan

Tokyo Medical University Hospital

Tokyo, , Japan

Toyama Prefectual Central Hospital

Toyama, , Japan

Amsterdam UMC, Locatie AMC

Amsterdam, , Netherlands

Szpital Uniwersytecki nr2 im. dr J. Biziela

Bydgoszcz, , Poland

Uniwersyteckie Centrum Kliniczne

Gda?sk, , Poland

Samodzielny Publiczny Szpital Kliniczny nr 1

Lublin, , Poland

Pratia Poznan

Skórzewo, , Poland

MTZ Clinical Research Powered by Pratia

Warsaw, , Poland

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

Aveiro, , Portugal

Centro Hospitalar do Porto - Hospital de Santo António

Porto, , Portugal

King Faisal Specialist Hospital & Research Center

Riyadh, , Saudi Arabia

National University Hospital

Singapore, , Singapore

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Ulsan University Hospital

Ulsan, , South Korea

ICO Badalona - Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Complejo Hospitalario Universitario de Santiago.

Santiago de Compostela, LA Coruna, Spain

Hospital U. Central de Asturias

Asturias, Principality of Asturias, Spain

Hospital de Basurto

Bilbao, Vizcaya, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario de Gran Canaria

Las Palmas, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Universitario Clinico San Carlos

Madrid, , Spain

Hospital Regional Universitario de Malaga

Málaga, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Universitario de Toledo

Toledo, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Akademiska Sjukhuset

Uppsala, , Sweden

Changhua Christian Hospital

Chang-hua, , Taiwan

Hualien Tzu Chi Hospital

Hualien City, , Taiwan

National Taiwan Universtiy Hospital

Taipei, , Taiwan

Hacettepe University Medical Faculty; Neurology

Ankara, , Turkey (Türkiye)

Gaziantep University Medical Faculty Sahinbey Educational Research Hospital; Hematology

Gaziantep, , Turkey (Türkiye)

Istanbul University Istanbul Medical Faculty; Neurology

Istanbul, , Turkey (Türkiye)

Marmara University Pendik Training and Research Hospital, Hematology Department

Istanbul, , Turkey (Türkiye)

Ege University Medical Faculty; Hematology

Izmir, , Turkey (Türkiye)

Ondokuz Mayis Univ. Med. Fac.

Samsun, , Turkey (Türkiye)

King'S College Hospital

London, , United Kingdom

Countries

United States; Belgium; Brazil; Canada; Czechia; Estonia; France; Germany; Greece; Hong Kong; Hungary; Ireland; Italy; Japan; Netherlands; Poland; Portugal; Saudi Arabia; Singapore; South Korea; Spain; Sweden; Taiwan; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40978458 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39535306 (View on PubMed)

Other Identifiers

2020-000597-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506526-37-00

Identifier Type: CTIS

Identifier Source: secondary_id

BO42161

Identifier Type: -

Identifier Source: org_study_id