PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) MedDRA version: 21.1 Level: PT Classification code 10034042 Term: Paroxysmal nocturnal haemoglobinuria System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
F.Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General Inclusion Criteria (All Patients) - 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) =65 years) yes F.1.3.1 Number of subjects for this age range 35
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) 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 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 <= 6 months prior to screening - Positive for hepatitis B surface antigen at screening - Positive for hepatitis C virus antibody at screening confirmed by detectable HCV RNA - History of or ongoing cryoglobulinemia at screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of crovalimab compared with eculizumab;Secondary Objective: • To characterize the crovalimab, eculizumab, and ravulizumab pharmacokinetics profile • To evaluate the immune response to crovalimab • To identify and/or evaluate biomarkers that can potentially provide evidence of crovalimab, eculizumab, and ravulizumab activity • To evaluate the efficacy of crovalimab compared with eculizumab ;Primary end point(s): 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;Timepoint(s) of evaluation of this end point: 1. Up to 8 years 2-3. From baseline to 8 years 4-5. Up to 8 years 6. From baseline to 8 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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;Timepoint(s) of evaluation of this end point: 1. Up to 8 years (crovalimab) and up to Week 25 (eculizumab) 2. At baseline 3. At baseline (prevalence) and up to 8 years (incidence) 4-6. Up to 8 years 7. From Baseline to Weeks 21, 23, 25 8-11. From Baseline to Week 25 13. At baseline (prevalence) and up to 7.5 years (incidence) 14-16 Up to 7.5 years | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, Colombia, Czechia, Czech Republic, Estonia, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Philippines, Poland, Portugal, Romania, Singapore, 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