A Randomized, Open-Label, C5 Inhibitor-Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Are Complement Inhibitor Treatment-Naive or Have Not Recently Received Complement Inhibitor Therapy

R3918-PNH-2021

The study is researching a clinical treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on patients with paroxysmal nocturnal hemoglobinuria (PNH). The aim of the study is to see how safe and effective the pozelimab + cemdisiran combination is for patients with PNH and how the combination compares with 2 existing treatments, one called ravulizumab and the other called eculizumab. The pozelimab + cemdisiran combination may be referred to as "study drugs". Ravulizumab and eculizumab may also be called the "comparator drug". The study is looking at several research questions, including: * How effective is the pozelimab + cemdisiran combination compared to ravulizumab? * How effective is pozelimab + cemdisiran combination compared to eculizumab? * What side effects may happen from taking the study drugs? * How much study drugs are in your blood at different times? * Whether the body makes antibodies against the study drugs (which could make the study drugs less effective or could lead to side effects)

2022-08-01

2027-03-01

2027-03-01

Recruiting

Early phase I

190

Key Inclusion Criteria: 1. Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes as described in the protocol 2. Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms as described in the protocol 3. LDH level ≥2 × ULN at the screening visit Key Exclusion Criteria: 1. Prior treatment with eculizumab within 3 months prior to screening, ravulizumab within 6 months prior to screening, or other complement inhibitors within 5 half-lives of the respective agent prior to screening 2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant 3. Body weight \<40 kilograms at screening visit 4. Planned use of any complement inhibitor therapy other than study drugs during the treatment period 5. Not meeting meningococcal vaccination requirements for ravulizumab (Cohort A) or eculizumab (Cohort B) 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. Unable to take antibiotics for meningococcal prophylaxis (if required by local ravulizumab \[Cohort A\] or eculizumab \[Cohort B\] prescribing information, where available, or national guidelines/local practice or if necessary when vaccination is less than 2 weeks from study treatment initiation) 8. Any active, ongoing infection or a recent infection requiring ongoing systemic treatment with antibiotics, antivirals, or antifungals within 2 weeks of screening or during the screening period 9. Documented history of active, uncontrolled, ongoing systemic autoimmune diseases Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 190, 'type': 'ESTIMATED'}}

2024-04-10