A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition
Crovalimab: Crovalimab will be administered at a dose of 1000 milligrams (mg) IV (for participants with body weight between 40 and 100 kg) or 1500 mg IV (for participants with body weight ≥ 100 kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, it will be administered at a dose of 340 mg SC. For Week 5 and Q4W thereafter, it will be administered at a dose of 680 mg SC (for participants with body weight between 40 and 100 kg) or 1020 mg SC (for participants with body weight ≥ 100 kg). Dosing schedule will be as described above.
Study summary
This study will enroll participants aged 12 years or older with a body weight ≥ 40 kilograms (kg) diagnosed with PNH who have not been previously treated with complement inhibitor therapy. Approximately 50 participants will be treated with Crovalimab for at least 24 weeks.
Eligibility
Sex
ALL
Min age
12 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Body weight ≥ 40 kg at screening
* Willingness and ability to comply with all study visits and procedures
* Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry
* LDH Levels ≥ 2x the ULN at screening
* Participants who have at least four transfusions during 12 months prior to screening (documented in the medical record)
* Presence of one or more of the PNH-related signs or symptoms within 3 months of screening
* Vaccination against Neisseria meningitidis serotypes A, C, W, and Y \< 3 years prior to initiation of study treatment (Day 1)
* Vaccination against Haemophilius influenzae type B and Streptococcus pneumonia according to national vaccination recommendations
* For participants receiving other therapies (e.g., immunosuppressants, corticosteroids): stable dose for ≥ 28 days prior to screening and up to the first drug administration
* Adequate hepatic and renal function
* Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 46 weeks (approximately 10.5 months) after the final dose of crovalimab
* Platelet count ≥30,000 per cubic millimeter (mm\^3) at screening
* ANC \> 500/microlitres (μl) at screening
Exclusion Criteria:
* Current or previous treatment with a complement inhibitor
* History of allogeneic bone marrow transplantation
* History of Neisseria meningitidis infection within 6 months prior to screening and up to first drug administration
* Known or suspected immune or hereditary complement deficiency
* Known HIV infection with cluster of differentiation 4 (CD4) count \< 200 cells/µl within 24 weeks prior to screening
* Infection requiring hospitalization or treatment with IV antibiotics within 28 days prior to screening and up to the first drug administration, or oral antibiotics within 14 days prior to screening and up to the first drug administration
* Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration
* Presence of fever (≥ 38˚C) within 7 days before the first drug administration
* Splenectomy \< 6 months before screening
* History of malignancy within 5 years prior to screening and up to the first drug administration
* Pregnant or intending to become pregnant during the study or within 46 weeks (10.5 months) after the final dose of study treatment
* 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 is greater
Primary outcome measure(s)
Mean Percentage of Participants With Hemolysis Control — From Week 5 up to Week 25 A Generalized Estimating Equation (GEE) was used to estimate the population-average percentage of the participants with hemolysis control (measured by lactate dehydrogenase (LDH) ≤1.5 x upper limit of normal (ULN)) from Week 5 to Week 25 taking account of the intra-patient and inter-patient correlation between LDH control statuses across visits. The dependent variable was the binary indicator for hemolysis control. Independent variables are categorical effects of visits, continuous baseline LDH.
Difference in Percentage of Participants With Transfusion Avoidance (TA) From Baseline Through Week 25 and Within 24 Weeks Prior to Screening — 24 Weeks Prior to Screening, Baseline to Week 25 TA was defined as participants who were packed red blood cell (pRBC) transfusion-free and did not require transfusion per protocol-specified guidelines. TA within 24 weeks prior to screening was based on the pRBC transfusion history in the medical records. Reported in this outcome measure is the difference in the percentage of participants between "baseline through Week 25" and "within 24 weeks prior to screening". 95% Confidence Interval (CI) for the difference between the percentage of participants with transfusion avoidance between Pre-screening and Post-baseline is calculated using the Newcombe method.
Screening= Day -28 to Day -1 and Baseline= Day 1.
Trial sites (5)
Facility
City
Region
Status
West China Hospital, Sichuan University
Chengdu
China
Guangdong General Hospital
Guangzhou
China
Institute of Hematology and Hospital of Blood Disease
Tianjin
China
Tianjin Medical University General Hospital
Tianjin
China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
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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