Paroxysmal Nocturnal HemoglobinuriaPhase 3COMMODORE 1NCT04432584
A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors
A Phase 3 study testing Crovalimab and Eculizumab in people with Paroxysmal Nocturnal Hemoglobinuria, run by Hoffmann-La Roche at 80 sites in 24 countries.
Trial 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. 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
- 190 participants
- Where
- 80 sitesin 24 countries
- Study dates
- 30 Sep 2020to 18 Apr 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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)
- 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)
Who cannot join
- 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
Trial locations and contacts
80 sites in 24 countries.
80 sites in 24 countries
Japan15 sites
Fujita Health University Hospital
Aichi, 470-1192
Kobe University Hospital
Hyōgo, 650-0017
Tokushukai Takasago Seibu Hospital
Hyōgo, 676-0812
Ishikawa Prefectural Central Hospital
Ishikawa, 920-8530
Tokai University Hospital
Kanagawa, 259-1193
Mie University Hospital
Mie, 514-8507
Japanese Red Cross Society Suwa Hospital
Nagano, 392-8510
Nagasaki University Hospital
Nagasaki, 852-8501
Sasebo City General Hospital
Nagasaki, 857-8511
National Hospital Organization Okayama Medical Center
Okayama, 701-1192
The University of Osaka Hospital
Osaka, 565-0871
Iwate Prefectural Isawa Hospital
Ōshū, 023-0864
NTT Medical Center Tokyo
Tokyo, 141-8625
Tokyo Medical University Hospital
Tokyo, 160-0023
Toyama Prefectual Central Hospital
Toyama, 930-8550
Spain11 sites
Hospital U. Central de Asturias
Asturias, Principality of Asturias, 33011
ICO Badalona - Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital de Basurto
Bilbao, Vizcaya, 48013
Hospital General Universitario Gregorio Marañon
Madrid, 28009
Hospital Regional Universitario de Malaga
Málaga, 29010
Hospital Universitario de Salamanca
Salamanca, 37007
Complejo Hospitalario Universitario de Santiago.
Santiago de Compostela, LA Coruna, 15706
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital Universitario de Toledo
Toledo, 45007
Hospital Universitario Miguel Servet
Zaragoza, 50009
Brazil9 sites
Instituto Joinvilense de Hematologia E Oncologia
Joinville, Santa Catarina, 89201-260
Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90020-090
Hospital de Clínicas de Porto Alegre X
Porto Alegre, Rio Grande do Sul, 90035-903
Hospital das Clínicas FMRP-USP
Ribeirão Preto, São Paulo, 14048-900
*X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
Santo André, São Paulo, 09060-870
Hospital Sírio-Libanês
São Paulo, São Paulo, 01308-050
Hospital Paulistano
São Paulo, São Paulo, 01321-000
Beneficencia Portuguesa de Sao Paulo
São Paulo, 01321-00
Chronos Pesquisa Clinica
Taguatinga, Federal District, 72145-450
Turkey (Türkiye)6 sites
Hacettepe University Medical Faculty; Neurology
Ankara, 06100
Gaziantep University Medical Faculty Sahinbey Educational Research Hospital; Hematology
Gaziantep, 27310
Istanbul University Istanbul Medical Faculty; Neurology
Istanbul, 34093
Marmara University Pendik Training and Research Hospital, Hematology Department
Istanbul, 34300
Ege University Medical Faculty; Hematology
Izmir, 35040
Ondokuz Mayis Univ. Med. Fac.
Samsun, 55139
Italy5 sites
Azienda Ospedaliera Universitaria Careggi
Florence, Tuscany, 50134
Fondazione IRCCS CA? Granda Ospedale Maggiore Policlinico
Milan, Lombardy, 20122
Azienda Unita Sanitaria Locale- Ravenna
Ravenna, Emilia-Romagna, 48121
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, Lazio, 00168
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Turin, Piedmont, 10126
Poland5 sites
Szpital Uniwersytecki nr2 im. dr J. Biziela
Bydgoszcz, 85-168
Uniwersyteckie Centrum Kliniczne
Gda?sk, 80-214
Samodzielny Publiczny Szpital Kliniczny nr 1
Lublin, 20-081
Pratia Poznan
Skórzewo, 60-185
MTZ Clinical Research Powered by Pratia
Warsaw, 02-172
South Korea4 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital
Seoul, 03722
Samsung Medical Center
Seoul, 06351
Ulsan University Hospital
Ulsan, 44033
Taiwan3 sites
Changhua Christian Hospital
Chang-hua, 500
Hualien Tzu Chi Hospital
Hualien City, DUMMY_VALUE
National Taiwan Universtiy Hospital
Taipei, 100
United States2 sites
Carolinas Healthcare System
Charlotte, North Carolina, 28204
Nationwide Children's Hospital
Columbus, Ohio, 43205
Belgium2 sites
Cliniques Universitaires Saint-Luc
Brussels, 1200
AZ Delta Campus Westlaan
Roeselare, 8800
France2 sites
Hopital Claude Huriez - CHU Lille
Lille, 59037
Institut Paoli Calmette
Marseille, 13273
Germany2 sites
Universitaetsklinikum Aachen AOeR
Aachen, 52074
ELBLANDKLINIKUM Riesa
Riesa, 01589
Greece2 sites
General Hospital of Athens LAIKO
Athens, 115 27
Attikon University General Hospital
Athens, 124 62
Portugal2 sites
Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro
Aveiro, 3814-501
Centro Hospitalar do Porto - Hospital de Santo António
Porto, 4099-001
Saudi Arabia1 site
King Faisal Specialist Hospital & Research Center
Riyadh, 11211
About this study
Official title: A Phase III, Randomized, Open-label, Active-controlled, Multicenter Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamic and Efficacy of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors
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
- 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 at a dose of 900 mg Q2W, as per the dosing schedule described above.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Crovalimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to approximately 6 years
Percentage of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis)
Measured: Up to approximately 6 years
Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation
Measured: 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
Measured: Up to approximately 6 years
Secondary outcomes (9)
Serum Concentrations of Crovalimab or Eculizumab Over Time
Measured: Up to approximately 6 years
Serum Concentrations of Ravulizumab at the Time of Crovalimab Initiation
Measured: Baseline
Percentage of Participants With Anti-crovalimab Antibodies
Measured: Up to approximately 6 years
Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time
Measured: Up to approximately 6 years
Change Over Time in Free C5 Concentration in Crovalimab-treated Participants
Measured: Up to approximately 6 years
Observed Value in Reticulocyte Count (count/milliliters [mL])
Measured: Up to approximately 6 years
Observed Value in Free Hemoglobin and Haptoglobin (milligrams per deciliter [mg/dL])
Measured: Up to approximately 6 years
Absolute Change From Baseline in Reticulocyte Count (count/mL)
Measured: Baseline up to Week 25
Absolute Change From Baseline in Free Hemoglobin and Haptoglobin (mg/dL)
Measured: Baseline up to Week 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 start30 Sep 2020
- Primary completion18 Apr 2027 (estimated)
- Study completion18 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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
- 190 participants (estimated)
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
- NCT04432584
- Sponsor's protocol ID
- BO42161
- Other IDs
- 2020-000597-26, 2023-506526-37-00, 2023
- Acronym
- COMMODORE 1
- Status last verified
- Oct 2026
- First submitted
- 3 Jun 2020
- Last updated
- 26 Oct 2026
- Results posted
- No
- 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
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.
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 39535306Scheinberg P, Cle DV, Kim JS, Nur E, Yenerel MN, Barcellini W, Bonito D, Giai V, Hus M, Lee Y, Lekue CB, Panse J, Ueda Y, Buatois S, Gentile B, Kiialainen A, Patel H, Sreckovic S, Uguen M, Edwards J, Nagy Z, Kulasekararaj AG. Phase 3 randomized COMMODORE 1 trial: Crovalimab versus eculizumab in complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2024 Sep;99(9):1757-1767. doi: 10.1002/ajh.27413. Epub 2024 Jun 25.
PubMed 38924124
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Open-label, Active-controlled, Multicenter Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamic and Efficacy of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors
- ClinicalTrials.gov ID
- NCT04432584
- Acronym / sponsor ID
- COMMODORE 1 / BO42161
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 190 participants (estimated)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Collaborators
- Chugai Pharmaceutical
- Study start
- 30 Sep 2020 (actual)
- Primary completion
- 18 Apr 2027 (estimated)
- Study completion
- 18 Apr 2027 (estimated)
- First posted
- 16 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A (Crovalimab) | Experimental | Drug: CrovalimabParticipants 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. |
| Arm B (Eculizumab) | Active comparator | Drug: EculizumabParticipants 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. |
| Arm C (Crovalimab) (Exploratory) | Experimental | Drug: CrovalimabParticipants 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. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CrovalimabDosing 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. | Drug | Arm A (Crovalimab), Arm C (Crovalimab) (Exploratory) |
| EculizumabEculizumab will be administered at a dose of 900 mg Q2W, as per the dosing schedule described above. | Drug | Arm B (Eculizumab) |
Primary outcome
Percentage of Participants With Adverse Events (AEs) and by Severity
Time frame: Up to approximately 6 years
Severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5 (CTCAE v5).
Percentage of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis)
Time frame: Up to approximately 6 years
Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation
Time frame: 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
Time frame: Up to approximately 6 years
9 secondary outcomes
Serum Concentrations of Crovalimab or Eculizumab Over Time
Time frame: Up to approximately 6 years
Serum Concentrations of Ravulizumab at the Time of Crovalimab Initiation
Time frame: Baseline
Percentage of Participants With Anti-crovalimab Antibodies
Time frame: Up to approximately 6 years
Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time
Time frame: Up to approximately 6 years
Change Over Time in Free C5 Concentration in Crovalimab-treated Participants
Time frame: Up to approximately 6 years
Observed Value in Reticulocyte Count (count/milliliters [mL])
Time frame: Up to approximately 6 years
Observed Value in Free Hemoglobin and Haptoglobin (milligrams per deciliter [mg/dL])
Time frame: Up to approximately 6 years
Absolute Change From Baseline in Reticulocyte Count (count/mL)
Time frame: Baseline up to Week 25
Absolute Change From Baseline in Free Hemoglobin and Haptoglobin (mg/dL)
Time frame: Baseline up to Week 25
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Derived from this study: PubMed 40978458Kulasekararaj 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.
- Derived from this study: PubMed 39535306Roth 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.
- Derived from this study: PubMed 38924124Scheinberg P, Cle DV, Kim JS, Nur E, Yenerel MN, Barcellini W, Bonito D, Giai V, Hus M, Lee Y, Lekue CB, Panse J, Ueda Y, Buatois S, Gentile B, Kiialainen A, Patel H, Sreckovic S, Uguen M, Edwards J, Nagy Z, Kulasekararaj AG. Phase 3 randomized COMMODORE 1 trial: Crovalimab versus eculizumab in complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2024 Sep;99(9):1757-1767. doi: 10.1002/ajh.27413. Epub 2024 Jun 25.
- Individual participant dataSharing planned: 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
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Paroxysmal Nocturnal Hemoglobinuria
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
80 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Crovalimab and Eculizumab in people with Paroxysmal Nocturnal Hemoglobinuria, run by Hoffmann-La Roche at 80 sites in 24 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 80 sites in Japan, Spain, Brazil, Turkey (Türkiye), Italy and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Adverse Events (AEs) and by Severity (time frame: Up to approximately 6 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04432584, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.