A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors
Phase 3
Active, not recruiting
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Interventions
- Registration Number
- NCT04432584
- Lead Sponsor
- Hoffmann-La Roche
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 190
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B (Eculizumab) Eculizumab 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. Arm A (Crovalimab) Crovalimab 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. Arm C (Crovalimab) (Exploratory) Crovalimab 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Adverse Events (AEs) and by Severity 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) Up to approximately 6 years Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation 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 Up to approximately 6 years
- Secondary Outcome Measures
Name Time Method Absolute Change From Baseline in Free Hemoglobin and Haptoglobin (mg/dL) Baseline up to Week 25 Serum Concentrations of Crovalimab or Eculizumab Over Time Up to approximately 6 years Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time Up to approximately 6 years Change Over Time in Free C5 Concentration in Crovalimab-treated Participants Up to approximately 6 years Observed Value in Reticulocyte Count (count/milliliters [mL]) Up to approximately 6 years Observed Value in Free Hemoglobin and Haptoglobin (milligrams per deciliter [mg/dL]) Up to approximately 6 years Absolute Change From Baseline in Reticulocyte Count (count/mL) Baseline up to Week 25 Serum Concentrations of Ravulizumab at the Time of Crovalimab Initiation Baseline Percentage of Participants With Anti-crovalimab Antibodies Up to approximately 6 years
Trial Locations
- Locations (80)
AZ Delta Campus Westlaan
🇧🇪Roeselare, Belgium
Fondazione IRCCS CA? Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Lombardia, Italy
Carolinas Healthcare System
🇺🇸Charlotte, North Carolina, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
CHU UCL Namur / site Godinne
🇧🇪Yvoir, Belgium
Chronos Pesquisa Clinica
🇧🇷Taguatinga, Distrito Federal, Brazil
Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital de Clínicas de Porto Alegre X
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Instituto Joinvilense de Hematologia E Oncologia
🇧🇷Joinville, Santa Catarina, Brazil
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