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

NCT04434092 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: BO421622019-004931-212023-506498-36-00
• Study Type: interventional
• Target: 210
• Locations: 23 countries
• Sites: 61

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (16)

• Percentage of Participants With Breakthrough Hemolysis (BTH)

  Baseline to Week 25

• Percentage of Participants With Stabilization of Hemoglobin

  Baseline to Week 25

• Change From Baseline in Fatigue Assessed by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale

  Baseline to Week 25

• Percentage of Participants With Adverse Events (AEs)

  Up to 6 years

• Percentage of Participants With Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (Including Meningococcal Meningitis)

  Up to 6 years

Study Arms (3)

Arm A (Crovalimab)

EXPERIMENTAL

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

Arm B (Eculizumab)

ACTIVE COMPARATOR

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: Crovalimab; Drug: Eculizumab

Arm C (Crovalimab) (Exploratory)

EXPERIMENTAL

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

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 B (Eculizumab); Arm C (Crovalimab) (Exploratory)

Eculizumab DRUG

Eculizumab will be administered as specified in the respective arm.

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)
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (61)

Organizacion Medica de Investigacion (OMI)

Ciudad Autonoma Buenos Aires, C1015ABO, Argentina

Location

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

Santo André, São Paulo, 09060-870, Brazil

Location

Beneficencia Portuguesa de Sao Paulo

São Paulo, 01321-00, Brazil

Location

Peking Union Medical College Hospital

Beijing, 100730, China

Location

Nanfang Hospital, Southern Medical University

Guangzhou, 510515, China

Location

The First Affiliated Hospital, Zhejiang University

Hangzhou, 310003, China

Location

Jiangsu Province Hospital

Nanjing, 210029, China

Location

Affiliated Hospital of Nantong University

Nantong, 226001, China

Location

Huashan Hospital, Fudan University

Shanghai, 200040, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430022, China

Location

Centre Hospitalier Lyon Sud

Pierre-Bnite, Rhone, 69310, France

Location

Hopital Claude Huriez - CHU Lille

Lille, 59037, France

Location

Universitaetsklinkm

Essen, 45147, Germany

Location

Universitaetsklinikum Ulm

Ulm, 89081, Germany

Location

General Hospital of Thessaloniki G. Papanikolaou

Thessaloniki, 570 10, Greece

Location

Sapporo Medical University Hospital

Hokkaido, 060-8543, Japan

Location

University of Tsukuba Hospital

Ibaraki, 305-8576, Japan

Location

NTT Medical Center Tokyo

Tokyo, 141-8625, Japan

Location

Tokyo Medical University Hospital

Tokyo, 160-0023, Japan

Location

Vilnius University Hospital Santariskiu Clinics, Public Institution

Vilnius, LT-08661, Lithuania

Location

Hospital Raja Permaisuri Bainun

Ipoh, Perak, 30450, Malaysia

Location

Hospital Ampang

Ampang, Selangor, 68000, Malaysia

Location

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, Mexico CITY (federal District), 14080, Mexico

Location

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

Monterrey, Nuevo León, 64718, Mexico

Location

Amsterdam UMC, Locatie AMC

Amsterdam, 1105 AZ, Netherlands

Location

Mary Mediatrix Medical Center

Lipa City, 4217, Philippines

Location

Philippine General Hospital

Manila, 1000, Philippines

Location

St Lukes Medical Center

Quezon, 1102, Philippines

Location

Szpital Uniwersytecki nr2 im. dr J. Biziela

Bydgoszcz, 85-168, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, 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, 3810-501, Portugal

Location

Instituto Portugues Oncologia de Lisboa Francisco Gentil EPE

Lisbon, 1099-023, Portugal

Location

Centro Hospitalar do Porto - Hospital de Santo António

Porto, 4099-001, Portugal

Location

Spitalul Universitar de Urgenta Bucuresti

Bucharest, 050098, Romania

Location

Spitalul Clinic Municipal Filantropia Craiova

Craiova, 200143, Romania

Location

National University Hospital

Singapore, 119074, Singapore

Location

Singapore General Hospital

Singapore, 169856, Singapore

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital de Basurto

Bilbao, Albacete, 48013, Spain

Location

ICO Badalona - Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario de Gran Canaria Dr. Negrin

Las Palmas de Gran Canaria, LAS Palmas, 35019, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, 10003, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Chang Gung Medical Foundation - Kaohsiung

Kaohisung, DUMMY_VALUE, Taiwan

Location

National Taiwan Universtiy Hospital

Taipei, 100, Taiwan

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200, Thailand

Location

Ondokuz Mayis Univ. Med. Fac.

Samsun, 55139, Turkey (Türkiye)

Location

Medical Center OK!Clinic+

Kyiv, KIEV Governorate, 02091, Ukraine

Location

St James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Kings 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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: October 8, 2020
• Primary Completion: November 16, 2022
• Study Completion (Estimated): September 30, 2027
• Last Updated: April 28, 2026
• Results First Posted: November 10, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

LI (1); PL (5); ME (2); ES (9); NL (1); KR (4); TU (1); GR (1); GB (2); AR (1); JP (4); CN (7); PH (3); BR (2); MY (2); PT (3); SG (2); TW (2); DE (2); TH (2); FR (2); UA (1); RO (2)