a study to evaluate how safe pozelimab + cemdisiran combination therapy is and how well it works in adult patients with paroxysmal nocturnal hemoglobinuria (pnh) who have not recently received or have not received complement inhibitor treatment

Conditions: Paroxysmal Nocturnal Hemoglobinuria

Summary: this study is researching a clinical treatment combination with two experimental drugs called pozelimab and cemdisiran. the study is focused on people with paroxysmal nocturnal hemoglobinuria (pnh). the aim of the study is to see how safe and effective the pozelimab + cemdisiran combination is for people with pnh and how the combination compares with 2 existing treatments: ravulizumab and 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 the 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)


Eligibility criteria:
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 4. willing and able to comply with clinic/remote visits and study-related procedures, including completion of the full series of meningococcal vaccinations required per protocol 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 and, at a minimum documentation of quadrivalent meningococcal vaccination within 5 years prior to the screening visit and serotype b vaccine within 3 years prior to the screening visit as described in the protocol. 6. any contraindication for receiving neisseria meningitidis vaccinations (serotypes acwy and b). 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 administration of the first dose of the quadrivalent meningococcal vaccine \[serotype acwy\] or the second dose of the serotype b meningococcal vaccine \[when available\] is less than 2 weeks prior to study treatment initiation) as described in the protocol 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

Keywords: pnh