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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
190
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 will be administered at a dose of 900 mg Q2W, as per the dosing schedule described above.
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).
Time frame: Up to approximately 6 years
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
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
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Carolinas Healthcare System
Charlotte, North Carolina, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Cliniques Universitaires Saint-Luc
Brussels, Belgium
AZ Delta Campus Westlaan
Roeselare, Belgium
CHU UCL Namur / site Godinne
Yvoir, Belgium
Chronos Pesquisa Clinica
Taguatinga, Federal District, 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
Hospital das Clínicas FMRP-USP
Ribeirão Preto, São Paulo, Brazil
...and 71 more locations
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