A Randomized, Open-label, Two-arm Study to Evaluate the Safety, Efficacy, and Pharmacodynamic Effects of Pozelimab and Cemdisiran Combination Treatment in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy

R3918-PNH-2092

The primary objective of the study is to evaluate the safety and tolerability of 2 dosing regimens of pozelimab and cemdisiran combination therapy during the open-label treatment period (OLTP) The secondary objectives of the study are: * To evaluate the effect of the combination treatment on the following parameters of intravascular hemolysis: lactate dehydrogenase (LDH) control, breakthrough hemolysis, and inhibition of total complement hemolysis activity (CH50) * To evaluate the effect of the combination treatment on hemoglobin levels * To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements * To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life * To assess the concentrations of total pozelimab in serum and total complement component (C) 5 and cemdisiran in plasma * To assess immunogenicity to pozelimab and cemdisiran * To evaluate the long-term safety and efficacy of pozelimab and cemdisiran in an optional open-label extension period (OLEP) * To assess safety after treatment intensification with pozelimab and cemdisiran

2021-07-29

2022-10-25

2023-10-18

Completed

Early phase I

24

Key Inclusion Criteria: 1. Participants with PNH who are receiving treatment with pozelimab monotherapy in the R3918- PNH-1868 study (NCT04162470) Key Exclusion Criteria: 1. Documented, positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as defined in the protocol 2. Participants with documented history of liver cirrhosis or participants with liver disease with evidence of currently impaired liver function; or participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) as described in the protocol 3. Significant protocol deviation(s) in the parent study based on the investigator's judgment as described in the protocol 4. Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the participant unsuitable for enrollment or would jeopardize the safety of the participant 5. Known hypersensitivity to cemdisiran or any component of cemdisiran formulation NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 24, 'type': 'ACTUAL'}}

2023-11-27