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

NCT ID: NCT04434092

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-08
• Study Completion Date: 2027-09-30

Brief Summary

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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Study Design

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

Study Groups

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.

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 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.

Group Type: ACTIVE_COMPARATOR

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.

Eculizumab

Intervention Type: DRUG

Eculizumab will be administered as specified in the respective arm.

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.

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 as specified in the respective arm.

Intervention Type: DRUG

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

• 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

Organizacion Medica de Investigacion (OMI)

Ciudad Autonoma Buenos Aires, , Argentina

Centro Integrado de Oncologia de Curitiba

Curitiba, Paraná, Brazil

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

Santo André, São Paulo, Brazil

Beneficencia Portuguesa de Sao Paulo

São Paulo, , Brazil

Peking Union Medical College Hospital

Beijing, , China

Nanfang Hospital, Southern Medical University

Guangzhou, , China

The First Affiliated Hospital, Zhejiang University

Hangzhou, , China

Jiangsu Province Hospital

Nanjing, , China

Affiliated Hospital of Nantong University

Nantong, , China

Huashan Hospital, Fudan University

Shanghai, , China

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, , China

Hopital Claude Huriez - CHU Lille

Lille, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Universitaetsklinkm

Essen, , Germany

Universitaetsklinikum Ulm

Ulm, , Germany

General Hospital of Thessaloniki G. Papanikolaou

Thessaloniki, , Greece

Sapporo Medical University Hospital

Hokkaido, , Japan

University of Tsukuba Hospital

Ibaraki, , Japan

NTT Medical Center Tokyo

Tokyo, , Japan

Tokyo Medical University Hospital

Tokyo, , Japan

Vilnius University Hospital Santariskiu Clinics, Public Institution

Vilnius, , Lithuania

Hospital Raja Permaisuri Bainun

Ipoh, Perak, Malaysia

Hospital Ampang

Ampang, Selangor, Malaysia

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, Mexico CITY (federal District), Mexico

Global Trial Research Center S.A. de C.V.

Monterrey, Nuevo León, Mexico

Amsterdam UMC, Locatie AMC

Amsterdam, , Netherlands

Mary Mediatrix Medical Center

Lipa City, , Philippines

Philippine General Hospital

Manila, , Philippines

St Lukes Medical Center

Quezon, , Philippines

Szpital Uniwersytecki nr2 im. dr J. Biziela

Bydgoszcz, , Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, , 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

Instituto Portugues Oncologia de Lisboa Francisco Gentil EPE

Lisbon, , Portugal

Centro Hospitalar do Porto - Hospital de Santo António

Porto, , Portugal

Spitalul Universitar de Urgenta Bucuresti

Bucharest, , Romania

Spitalul Clinic Municipal Filantropia Craiova

Craiova, , Romania

National University Hospital

Singapore, , Singapore

Singapore General Hospital

Singapore, , Singapore

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospital de Basurto

Bilbao, Albacete, Spain

ICO Badalona - Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital Universitario de Gran Canaria Dr. Negrin

Las Palmas de Gran Canaria, LAS Palmas, Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital San Pedro de Alcantara

Cáceres, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Universitario Clinico San Carlos

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Chang Gung Medical Foundation - Kaohsiung

Kaohisung, , Taiwan

National Taiwan Universtiy Hospital

Taipei, , Taiwan

Siriraj Hospital

Bangkok, , Thailand

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

King Chulalongkorn Memorial Hospital

Pathum Wan, , Thailand

Ondokuz Mayis Univ. Med. Fac.

Samsun, , Turkey (Türkiye)

Medical Center OK!Clinic+

Kyiv, KIEV Governorate, Ukraine

St James University Hospital

Leeds, , United Kingdom

Kings College Hospital

London, , United Kingdom

Countries

Australia; Belgium; Canada; Chile; Colombia; Czechia; Estonia; Hong Kong; Hungary; Ireland; Israel; Italy; Peru; Saudi Arabia; South Africa; Sweden; United States; Argentina; Brazil; China; France; Germany; Greece; Japan; Lithuania; Malaysia; Mexico; Netherlands; Philippines; Poland; Portugal; Romania; Singapore; South Korea; Spain; Taiwan; Thailand; Turkey (Türkiye); Ukraine; 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)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-004931-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506498-36-00

Identifier Type: CTIS

Identifier Source: secondary_id

BO42162

Identifier Type: -

Identifier Source: org_study_id