Paroxysmal Nocturnal Hemoglobinuria (PNH) MedDRA version: 21.1 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
F. Hoffman-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Body weight >= 40 kg - Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry evaluation of WBCs - LDH level >=2 x ULN at screening (as per local assessment) - Vaccination against Neisseria meningitidis serotypes A, C, W, and Y = 30,000/mm*3 at screening without transfusion support within 7 days of lab testing. - ANC > 500/micro L at screening - For female patients of childbearing potential: agreement to remain abstinent or use contraception Additional Inclusion Criteria for Patients in the Randomized Arms -Age >=18 years Additional Inclusion Criteria for Patients in the Descriptive Arm - Age =65 years) no F.1.3.1 Number of subjects for this age range 37
Exclusion criteria
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 study drug administration - 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 or within 46 weeks (approximately 10.5 months) after the final dose of crovalimab, or 3 months after final dose of eculizumab (or longer if required by the local product label) - 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 patient, or would, in the opinion of the Investigator, preclude the patient’s safe participation in and completion of the study - Splenectomy <= 6 months prior to screening - Positive for hepatitis B surface antigen at screening - Positive for hepatitis C virus antibody at screening (confirmed by detectable viral RNA) - History of or ongoing cryoglobulinemia at screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of crovalimab compared to eculizumab;Secondary Objective: • To evaluate the efficacy of crovalimab compared with eculizumab • To evaluate the overall safety and tolerability of crovalimab compared to eculizumab • To evaluate the pharmacokinetics of crovalimab and eculizumab • To evaluate the immune response to crovalimab • To identify and/or evaluate biomarkers that can potentially provide evidence of crovalimab and eculizumab activity ;Primary end point(s): 1. Proportion of patients who achieve transfusion avoidance 2. Proportion of patients with hemolysis control, measured by LDH <=1.5×ULN ;Timepoint(s) of evaluation of this end point: 1. From Baseline to Week 25 2. From Week 5 to Week 25 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of patients with breakthrough hemolysis 2. Proportion of patients with stabilization of hemoglobin 3. Mean change in fatigue, as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue 4. Incidence and severity of adverse events 5. Change from baseline in targeted vital signs 6. Change from baseline in targeted clinical laboratory test results 7. Incidence and severity of injection-site reactions, infusion-related reactions, hypersensitivity, and infections 8. Incidence of adverse events leading to study drug discontinuation 9. Incidence and severity of clinical manifestations of drug-target-drug complex formation in patients who switched to crovalimab treatment from eculizumab treatment 10. Serum concentration of crovalimab and eculizumab 11. Prevalence and incidence of anti-drug antibodies (ADAs) to crovalimab 12. Change over time in pharmacodynamic biomarkers 13. Change over time in free C5 concentration in crovalimab-treated patients 14. Observed value and absolute change from baseline to Week 25 in parameters reflecting hemolysis ;Timepoint(s) of evaluation of this end point: 1-3. From baseline to Week 25 4-9. Up to 7 years 10. Up to 7 years (crovalimab) and up to Week 25 (eculizumab) 11. At baseline (prevalence) and up to 7 years (incidence) 12-13. Up to 7 years 14. From baseline to Week 25 | — |
Countries
Argentina, Australia, Belgium, Brazil, China, Colombia, Czechia, Estonia, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Lithuania, Malaysia, Mexico, Netherlands, Peru, Philippines, Poland, Portugal, Romania, South Africa, Spain, Sweden, Taiwan, Thailand, Türkiye, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed