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

Sponsor
Hoffmann-La Roche
Study ID
NCT04434092
Phase
PHASE3
Status
Active Not Recruiting

Conditions

  • Paroxysmal Nocturnal Hemoglobinuria

Eligibility Criteria

Sex
ALL
Age
2 Years - N/A
Healthy Volunteers
Not accepted

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.
  • Eculizumab — DRUG
    Eculizumab will be administered as specified in the respective arm.

Study Details

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.

Key Dates

Start date
Oct 8, 2020
Status verified
Apr 2026
Primary completion
Nov 16, 2022
Completion
Sep 30, 2027

Study Design

Enrollment
210 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: 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.
  • Active Comparator: 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.
  • Experimental: 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.

Primary Outcome Measure

Percentage of Participants With Transfusion Avoidance (TA) [ Time Frame: Baseline to Week 25 ]

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