a study in adult patients with paroxysmal nocturnal hemoglobinuria (pnh) to evaluate how safe long-term treatment with pozelimab + cemdisiran combination therapy is and how well it works.

Conditions: Paroxysmal Nocturnal Hemoglobinuria

Summary: this study is researching an experimental treatment combination with two experimental drugs called pozelimab and cemdisiran. the study is focused on patients with paroxysmal nocturnal hemoglobinuria (pnh). the aim of this study is to see how safe and effective the pozelimab + cemdisiran combination is for patients with pnh in the long term. the pozelimab + cemdisiran combination may be referred to as "study drugs" in this section. this study is looking at several other research questions, including: * how effective is the pozelimab + cemdisiran combination? * what side effects may happen from taking the study drugs? * how much of each study drug is in the blood at different times? * whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects)


Eligibility criteria:
key inclusion criteria: patients entering from the parent study 1. patients with pnh who have completed, without permanent discontinuation, study treatment in the parent study (r3918-pnh-2021\[nct05133531\]), including the post-open-label treatment period (oltp) transition period, if applicable. 2. willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol. patients entering with c5 polymorphism 1. patients with pnh who have a documented c5 polymorphism rendering them refractory to eculizumab or ravulizumab (eg, p.arg885his, p.arg885cys), as described in the protocol 2. diagnosis of pnh confirmed by high-sensitivity flow cytometry testing with pnh granulocytes or monocytes 3. active disease, as defined by the presence of 1 or more pnh-related sign or symptom as described in the protocol 4. ldh level ≥2 × upper limit of normal (uln) at the screening visit 5. willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol key exclusion criteria: patients entering from the parent study 1. significant protocol deviation(s) in the parent study based on the investigator's judgment and to the extent that these would (if continued) impact the study objectives and/or safety of the patient 2. any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in or completing the study patients entering with c5 polymorphism 1. prior treatment with complement inhibitors within 5 half-lives of the respective agent prior to screening, except for prior eculizumab or ravulizumab which are not exclusionary 2. receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant 3. not meeting meningococcal vaccination requirements and, at a minimum, documentation of quadrivalent meningococcal vaccination within 5 years prior to enrollment and serotype b vaccine within 3 years prior to enrollment as described in the protocol 4. positive hepatitis b surface antigen or hepatitis c virus ribonucleic acid (rna) during screening 5. patients with known hiv with history of opportunistic infections in the last 1 year as described in the protocol 6. known hereditary complement deficiency 7. documented history of active, uncontrolled, ongoing systemic autoimmune diseases 8. documented history of liver cirrhosis or patients with liver disease with evidence of current impaired liver function or patients with elevations in alanine aminotransferase (alt) or aspartate aminotransferase (ast) (unrelated to pnh or its complications) as described in the protocol note: other protocol-defined inclusion/ exclusion criteria apply

Keywords: pnh