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

Launched by REGENERON PHARMACEUTICALS · Feb 22, 2023

Keywords

ClinConnect Summary

This clinical trial is studying the safety and effectiveness of a new combination treatment using two experimental drugs called pozelimab and cemdisiran for adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare blood condition. The trial aims to see how well this combination works over a long period and to understand any side effects that may occur. Participants will be monitored to check how much of each drug is in their bloodstream and whether their bodies develop antibodies that might affect the treatment's effectiveness.

To join the study, participants must be adults diagnosed with PNH, either coming from a prior study or having a specific genetic change that makes standard treatments ineffective. They should be willing to attend regular clinic visits and receive certain vaccinations. Throughout the trial, participants can expect close monitoring and support from the research team, helping to ensure their safety and well-being during the study.

Gender

ALL

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