Paroxysmal Nocturnal HemoglobinuriaPhase 3COMMODORE 2NCT04434092
A Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors
A Phase 3 study testing Crovalimab and Eculizumab in people with Paroxysmal Nocturnal Hemoglobinuria, run by Hoffmann-La Roche at 63 sites in 23 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria
- What is being tested?
- Crovalimab and Eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 63 sitesin 23 countries
- Study dates
- 8 Oct 2020to 18 Apr 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
63 sites in 23 countries.
63 sites in 23 countries
Spain9 sites
ICO Badalona - Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital de Basurto
Bilbao, Albacete, 48013
Hospital San Pedro de Alcantara
Cáceres, 10003
Hospital Universitario de Gran Canaria Dr. Negrin
Las Palmas de Gran Canaria, LAS Palmas, 35019
Hospital General Universitario Gregorio Marañon
Madrid, 28007
Hospital Universitario Clinico San Carlos
Madrid, 28040
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario de Salamanca
Salamanca, 37007
China7 sites
Peking Union Medical College Hospital
Beijing, 100730
Nanfang Hospital, Southern Medical University
Guangzhou, 510515
The First Affiliated Hospital, Zhejiang University
Hangzhou, 310003
Jiangsu Province Hospital
Nanjing, 210029
Affiliated Hospital of Nantong University
Nantong, 226001
Huashan Hospital, Fudan University
Shanghai, 200040
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, 430022
Poland5 sites
Szpital Uniwersytecki nr2 im. dr J. Biziela
Bydgoszcz, 85-168
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952
Samodzielny Publiczny Szpital Kliniczny nr 1
Lublin, 20-081
Pratia Poznan
Skórzewo, 60-185
MTZ Clinical Research Powered by Pratia
Warsaw, 02-172
Japan4 sites
Sapporo Medical University Hospital
Hokkaido, 060-8543
University of Tsukuba Hospital
Ibaraki, 305-8576
NTT Medical Center Tokyo
Tokyo, 141-8625
Tokyo Medical University Hospital
Tokyo, 160-0023
Malaysia4 sites
Hospital Ampang
Ampang, Selangor, 68000
Hospital Pulau Pinang
George Town, Pulau Pinang, 10990
Hospital Raja Permaisuri Bainun
Ipoh, Perak, 30450
Hospital Tengku Ampuan Afzan
Kuantan, 25100
South Korea4 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Philippines3 sites
Mary Mediatrix Medical Center
Lipa City, 4217
Philippine General Hospital
Manila, 1000
St Lukes Medical Center
Quezon, 1102
Portugal3 sites
Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro
Aveiro, 3810-501
Instituto Portugues Oncologia de Lisboa Francisco Gentil EPE
Lisbon, 1099-023
Centro Hospitalar do Porto - Hospital de Santo António
Porto, 4099-001
Brazil2 sites
*X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
Santo André, São Paulo, 09060-870
Beneficencia Portuguesa de Sao Paulo
São Paulo, 01321-00
France2 sites
Hopital Claude Huriez - CHU Lille
Lille, 59037
Centre Hospitalier Lyon Sud
Pierre-Bnite, Rhone, 69310
Germany2 sites
Universitaetsklinkm
Essen, 45147
Universitaetsklinikum Ulm
Ulm, 89081
Mexico2 sites
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Mexico City, Mexico CITY (federal District), 14080
Global Trial Research Center S.A. de C.V.
Monterrey, Nuevo León, 64718
Romania2 sites
Spitalul Universitar de Urgenta Bucuresti
Bucharest, 050098
Spitalul Clinic Municipal Filantropia Craiova
Craiova, 200143
Singapore2 sites
National University Hospital
Singapore, 119074
Singapore General Hospital
Singapore, 169856
Taiwan2 sites
Chang Gung Medical Foundation - Kaohsiung
Kaohisung, DUMMY_VALUE
National Taiwan Universtiy Hospital
Taipei, 100
Thailand2 sites
Siriraj Hospital
Bangkok, 10700
Maharaj Nakorn Chiang Mai Hospital
Chiang Mai, 50200
United Kingdom2 sites
St James University Hospital
Leeds, LS9 7TF
Kings College Hospital
London, SE5 9RS
Argentina1 site
Organizacion Medica de Investigacion (OMI)
Ciudad Autonoma Buenos Aires, C1015ABO
Greece1 site
General Hospital of Thessaloniki G. Papanikolaou
Thessaloniki, 570 10
Lithuania1 site
Vilnius University Hospital Santariskiu Clinics, Public Institution
Vilnius, LT-08661
About this study
Official title: A Phase III, Randomized, Open-label, Active-controlled, Multicenter Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors
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
- Being tested
- Crovalimab, Eculizumab
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CrovalimabDrug
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.
EculizumabDrug
Eculizumab will be administered as specified in the respective arm.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Crovalimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Week 5 to Week 25
Secondary outcomes (16)
Percentage of Participants With Breakthrough Hemolysis (BTH)
BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin < 10 grams per deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2xULN after a prior LDH reduction to ≤1.5xULN from the start of study treatment. 95% CI for percentage of participants with BTH was calculated using the Wilson's method with continuity correction. Participants who withdrew before Week 25 were deemed to have experienced a BTH event. Percentages are rounded off to the nearest single decimal.
Measured: Baseline to Week 25
Percentage of Participants With Stabilization of Hemoglobin
Stabilized hemoglobin is defined as avoidance of a >= 2 g/dL decrease in hemoglobin level from baseline, in the absence of transfusion. 95% CI for percentage of participants with stabilized hemoglobin was calculated using the Wilson's method with continuity correction. Participants who withdrew before Week 25 were deemed to not have had hemoglobin stabilization. Percentages are rounded off to the nearest single decimal.
Measured: Baseline to Week 25
Change From Baseline in Fatigue Assessed by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale
Fatigue was assessed using FACIT-F scale. FACIT-F is a self-assessment questionnaire with a 7-day recall period and 13 items evaluating fatigue and its impact on daily life activities. Items are scored on a response scale that ranges from 0 ("not at all") to 4 ("very much so"). Relevant items are reverse scored, and all the items are summed to create a total score range from 0 to 52, with 0 being the worst possible score and 52 being the best possible score. A higher score indicates low fatigue severity. A positive mean change indicates improvement. FACIT-F was assessed in adult participants only.
Measured: Baseline to Week 25
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs are reported based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
Measured: Up to 6 years
Percentage of Participants With Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (Including Meningococcal Meningitis)
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Injection-site reactions or infusion-related reaction are AEs related to the injection site that occur during or within 24 hours after study drug administration that are judged to be related to the study drug injection.
Measured: Up to 6 years
Percentage of Participants With AEs Leading to Study Drug Discontinuation
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs are reported based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
Measured: Up to 6 years
Percentage of Participants With Clinical Manifestations of Drug-Target-Drug Complex (DTDC) Formation Amongst Participants Who Switched to Crovalimab Treatment From Eculizumab Treatment
Measured: Up to 6 years
Serum Concentrations of Crovalimab And Eculizumab Over Time
Measured: Up to 6 years
Percentage of Participants With Anti-Crovalimab Antibodies
Measured: Up to 6 years
Change in Pharmacodynamic (PD) Biomarkers Including Complement Activity (CH50) Over Time
Measured: Up to 6 years
Change Over Time in Free C5 Concentration in Crovalimab-Treated Participants
Measured: Up to 6 years
Observed Value in Reticulocyte Count (Count/Milliliters [mL])
Measured: Up to 6 years
Observed Value in Haptoglobin (Milligrams Per Deciliter [mg/dL])
Measured: Up to 6 years
Change From Baseline in Absolute Reticulocyte Count
Measured: Baseline, Day 1 Week 1, Week 2, 3, 4, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23 and 25
Change From Baseline in Free Hemoglobin
Measured: Baseline, Week 2, 3, 4, 5, 9, 13, 17, 21, and 25
Change From Baseline in Haptoglobin
Measured: Baseline, Week 2, 3, 4, 5, 9, 13, 15, 17, 21, and 25
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start8 Oct 2020
- Primary completion16 Nov 2022
- Study completion18 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Paroxysmal Nocturnal HemoglobinuriaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 210 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Chugai Pharmaceutical
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04434092
- Sponsor's protocol ID
- BO42162
- Other IDs
- 2019-004931-21, 2023-506498-36-00, 2023, 2019
- Acronym
- COMMODORE 2
- Status last verified
- Jul 2026
- First submitted
- 3 Jun 2020
- Last updated
- 18 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Tong H, Lin Z, Yang C, Wang X, Sun J, Xia L, Shi J, Shi D, Zhang Z, Appius A, He G. Efficacy and safety of crovalimab versus eculizumab in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria: Chinese subgroup analysis of the phase 3 COMMODORE 2 study. Ann Hematol. 2026 Jun 13. doi: 10.1007/s00277-026-07129-3. Online ahead of print.
PubMed 42287326Kulasekararaj 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.
PubMed 40978458Roth 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.
PubMed 39535306Roth A, He G, Tong H, Lin Z, Wang X, Chai-Adisaksopha C, Lee JH, Brodsky A, Hantaweepant C, Dumagay TE, Demichelis-Gomez R, Rojnuckarin P, Sun J, Hoglund M, Jang JH, Gaya A, Silva F, Obara N, Kelly RJ, Beveridge L, Buatois S, Chebon S, Gentile B, Lundberg P, Sreckovic S, Nishimura JI, Risitano A, Han B. Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition. Am J Hematol. 2024 Sep;99(9):1768-1777. doi: 10.1002/ajh.27412. Epub 2024 Jun 17.
PubMed 38884175