A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors
Crovalimab: 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: Eculizumab will be administered at a dose of 900 mg Q2W, as per the dosing schedule described above.
Study 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.
Eligibility
Sex
ALL
Min age
2 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
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
Trial sites (80)
Facility
City
Region
Status
Carolinas Healthcare System
Charlotte
North Carolina
Nationwide Children's Hospital
Columbus
Ohio
Cliniques Universitaires Saint-Luc
Brussels
Belgium
AZ Delta Campus Westlaan
Roeselare
Belgium
Chronos Pesquisa Clinica
Taguatinga
Federal District
Santa Casa de Misericordia de Porto Alegre
Porto Alegre
Rio Grande do Sul
Hospital de Clínicas de Porto Alegre X
Porto Alegre
Rio Grande do Sul
Instituto Joinvilense de Hematologia E Oncologia
Joinville
Santa Catarina
Hospital das Clínicas FMRP-USP
Ribeirão Preto
São Paulo
*X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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