Paroxysmal nocturnal hemoglobinuria (PNH) MedDRA version: 21.1 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857
Conditions
Sponsors
Regeneron Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing 2. Treated with eculizumab or ravulizumab prior to screening visit as described in the protocol Note: Biosimilars are not permitted, unless approved by the Sponsor Note: Other protocol-defined Inclusion Criteria apply Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 112 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: 1. Patients with a screening LDH >1.5 × ULN who have not taken their C5 inhibitor within the labeled dose interval at the dose prior to the screening LDH assessment 2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant 3. Body weight < 40 kilograms at screening visit 4. Any use of complement inhibitor therapy other than eculizumab or ravulizumab in the 26 weeks prior to the screening visit or planned use during the study with the exception of study treatments 5. Not meeting meningococcal vaccination requirements for eculizumab or ravulizumab according to the current local prescribing information (where available) and at a minimum documentation of meningococcal vaccination within 5 years prior to screening visit. 6. Any contraindication for receiving Neisseria meningitidis vaccination. 7. Positive for hepatitis B, and/ or hepatitis C as described in the protocol 8. History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer 9. Participation in another interventional clinical study (except R3918-PNH-2021) or use of any experimental therapy within 30 days before screening visit or within 5 half-lives of that investigational product, whichever is greater, with the exception of eculizumab or ravulizumab. 10. Patients with functional or anatomic asplenia Note: Other protocol-defined Exclusion Criteria apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the effect of pozelimab and cemdisiran combination therapy on hemolysis, as assessed by LDH, after 36 weeks of treatment, in patients with PNH who switch from eculizumab or ravulizumab therapy versus patients who continue their eculizumab or ravulizumab therapy.;Secondary Objective: • Evaluate the effect of pozelimab and cemdisiran combination treatment versus anti-C5 standard-of-care treatment (eculizumab or ravulizumab) on the following: - Transfusion requirements and transfusion parameters - Measures of hemolysis: LDH control, breakthrough hemolysis, and inhibition of CH50 - Hemoglobin levels - Fatigue as assessed by Clinical Outcome Assessments (COAs) - HRQoL as assessed by COAs - Safety and tolerability • To assess the concentrations of total pozelimab and either total eculizumab or total ravulizumab in serum and total cemdisiran and total C5 protein in plasma • To assess the immunogenicity of pozelimab and cemdisiran;Primary end point(s): Percent change in lactate dehydrogenase (LDH);Timepoint(s) of evaluation of this end point: From baseline to week 36 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of patients with transfusion avoidance 2. Proportion of patients with transfusion avoidance 3. Proportion of patients with breakthrough hemolysis 4. Proportion of patients with breakthrough hemolysis 5. Proportion of patients with hemoglobin stabilization 6. Proportion of patients with hemoglobin stabilization 7. Proportion of patients with adequate control of LDH 8. Proportion of patients with adequate control of LDH 9. Proportion of patients with normalization of LDH 10. Proportion of patients with normalization of LDH 11. Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale 12. Change in Physical Function (PF) score on the European organization for research and treatment of cancer quality-of-Life questionnaire Core 30 Items (EORTC-QLQ-C30) 13. Change in global health status (GHS)/QoL scale score on the EORTC-QLQ-C30 14. Rate of RBCs transfused per protocol algorithm 15. Rate of RBCs transfused per protocol algorithm 16. Number of units of RBCs transfused per protocol algorithm 17. Number of units of RBCs transfused per protocol algorithm 18. Change in hemoglobin levels 19. Incidence and severity of treatment emergent serious adverse events (SAEs) 20. Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest 21. Incidence and severity TEAEs leading to treatment discontinuation 22. Change in total CH50 23. Percent change in total CH50 24. Concentration of total C5 in plasma 25. Concentrations of total pozelimab in serum 26. Concentrations of total cemdisiran in plasma 27. Concentrations of total eculizumab 28. Concentrations of total ravulizumab in serum 29. Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab 30. Incidence of treatment emergent ADAs to cemdisiran;Timepoint(s) of evaluation of this end point: 1. Day 1 through week 36 2. Week 4 through week 36 3. Day 1 through week 36 4. Week 4 (day 29) through week | — |
Countries
Brazil, Colombia, France, Germany, Greece, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Philippines, Poland, Portugal, Romania, Singapore, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Regeneron Pharmaceuticals, Inc.
Outcome results
None listed