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NCT Number: NCT04432584

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 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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Paroxysmal Nocturnal Hemoglobinuria Anemia Anemia, Hemolytic Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinuria, Paroxysmal Myelodysplastic Syndromes

Age range

2 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Cliniques Universitaires Saint-Luc, Brussels, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Eculizumab

Drug

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

Primary outcomes

  1. 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).

  2. Percentage of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis)

    Time frame: Up to approximately 6 years

  3. Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation

    Time frame: Up to approximately 6 years

  4. 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

Secondary outcomes

  1. Serum Concentrations of Crovalimab or Eculizumab Over Time

    Time frame: Up to approximately 6 years

  2. Serum Concentrations of Ravulizumab at the Time of Crovalimab Initiation

    Time frame: Baseline

  3. Percentage of Participants With Anti-crovalimab Antibodies

    Time frame: Up to approximately 6 years

  4. Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time

    Time frame: Up to approximately 6 years

  5. Change Over Time in Free C5 Concentration in Crovalimab-treated Participants

    Time frame: Up to approximately 6 years

  6. Observed Value in Reticulocyte Count (count/milliliters [mL])

    Time frame: Up to approximately 6 years

  7. Observed Value in Free Hemoglobin and Haptoglobin (milligrams per deciliter [mg/dL])

    Time frame: Up to approximately 6 years

  8. Absolute Change From Baseline in Reticulocyte Count (count/mL)

    Time frame: Baseline up to Week 25

  9. Absolute Change From Baseline in Free Hemoglobin and Haptoglobin (mg/dL)

    Time frame: Baseline up to Week 25

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Collaborators

  • Chugai Pharmaceutical

Registry information

Official study 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

Acronym: COMMODORE 1

Important dates

Study start
2020
Primary completion
2027
Study completion
2027
First posted
Jun 16, 2020
Registry last updated
Jul 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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