Paroxysmal nocturnal hemoglobinuria PNH
Conditions
Interventions
Subjects will be randomized 1:1 to crovalimab (Arm A) versus eculizumab (Arm B)
or will be assigned to Arm C if younger than 18 or if they meet specific
criteria.
For participants in Arm A and C we
Sponsors
F. Hoffmann- La Roche Ltd
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
Inclusion criteria: Body weight >= 40 kg - Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry evaluation of WBCs, - 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 For Patients in Randomized Arms (Arm A and B) - Age >= 18 years - Documented treatment with eculizumab according to the approved dosing recommended for PNH and completion of a minimum of 24 weeks of treatment prior to Day 1 - Lactate dehydrogenase (LDH)
Exclusion criteria
Exclusion criteria: - Major Adverse Vascular Event within 6 months prior to first drug administration (Day 1) - History of allogeneic bone marrow transplantation, - 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) prognosticrisk 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 the 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Incidence and severity of adverse events 2. Change from baseline in targeted vital signs 3. Change from baseline in targeted clinical laboratory test results 4. Incidence and severity of injection-site reactions, infusion-related reactions, hypersensitivity, and infections 5. Incidence of adverse events leading to study drug discontinuation 6. Incidence and severity of clinical manifestations of drug-target-drug complex formation in patients who switched to crovalimab treatment from eculizumab or ravulizumab treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Serum concentration of crovalimab or eculizumab 2. Serum concentration of ravulizumab 3. Prevalence and incidence of anti-drug antibodies (ADAs) to crovalimab 4. Change over time in pharmacodynamic biomarkers 5. Change over time in free C5 concentration in crovalimab-treated patients 6. Observed value and absolute change in parameters reflecting hemolysis 7. Percent change from baseline in LDH level averaged over Weeks 21, 23, and 25 LDH measurements 8. Proportion of patients with transfusion avoidance 9. Proportion of patients with breakthrough hemolysis 10. Proportion of patients with stabilization of hemoglobin 11. Mean change in fatigue as assessed through use of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale | — |
Countries
Netherlands
Outcome results
None listed