A Study to Examine the Long-term Safety, Tolerability, and Effectiveness of Pozelimab and Cemdisiran Combination Therapy in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria

• Status: Not yet recruiting
• Trial end date: 2028-03-27
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of the study is to describe the long-term safety, tolerability, and efficacy of pozelimab and cemdisiran combination therapy in patients with PNH

The secondary objectives of the study are to describe the long-term effect of the combination of pozelimab and cemdisiran on:

• Measures of intravascular hemolysis

• Transfusion parameters

• Hemoglobin levels

• Fatigue as assessed by a Patient Reported Outcome (PRO)

• Physical Function (PF) as assessed by a PRO

• Change in Global Health Status (GHS) as assessed by a PRO

• Complement activation

• Concentrations of total pozelimab in serum and cemdisiran and total complement component 5 (C5) protein in plasma

• Immunogenicity of pozelimab & cemdisiran

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Regeneron Pharmaceuticals

Criteria

Key Inclusion Criteria:

Patients Entering from the Parent Studies

1. Patients with PNH who have completed, without permanent discontinuation, study treatment in at least 1 of the parent studies (R3918-PNH-2021[NCT05133531] and/or R3918-PNH-2022 [NCT05131204]), if applicable.

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

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

Key Exclusion Criteria:

Patients Entering from the Parent Studies

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. No documentation of meningococcal vaccination within 5 years prior to enrollment

4. Positive hepatitis B surface antigen or hepatitis C virus 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 ALT or AST (unrelated to PNH or its complications) as described in the protocol

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply