Pozelimab and Cemdisiran Combination Therapy in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Switch From Eculizumab Therapy

Regeneron Pharmaceuticals

Status and phase

Completed

Phase 2

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Treatments

Drug: Pozelimab

Drug: Cemdisiran

Study type

Interventional

Funder types

Industry

Identifiers

NCT04888507

R3918-PNH-20105

2020-005006-25 (EudraCT Number)

Details and patient eligibility

About

The primary objective of the study is to evaluate the safety and tolerability of pozelimab and cemdisiran combination therapy in participants with PNH who switch from eculizumab therapy

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 CH50
To evaluate the effect of the combination treatment on the stability of LDH during the transition period from eculizumab monotherapy to combination with pozelimab and cemdisiran
To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements
To evaluate the effect of the combination treatment on hemoglobin levels
To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life (HRQoL)
To assess the concentrations of total pozelimab and eculizumab in serum; and total cemdisiran and C5 protein in plasma
To assess the immunogenicity of pozelimab and cemdisiran
To assess safety after dose intensification
To evaluate the long-term safety and efficacy of the combination treatment in an optional open-label extension period (OLEP)

Enrollment

6 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

Diagnosis of paroxysmal nocturnal hemoglobinuria confirmed by a history of high-sensitivity flow cytometry from prior testing
Treated with stable (ie, no change in dose or frequency) eculizumab therapy at the labeled dosing regimen or a higher dose and/or more frequently administered than labeled for at least 12 weeks prior to screening visit

Key Exclusion Criteria:

History of bone marrow transplantation or receipt of an organ transplant
Body weight <40 kg at screening
Current plans for modification of the following background concomitant medications, as applicable, during screening and treatment period: erythropoietin, immunosuppressive drugs, corticosteroids, anti-thrombotic agents, anticoagulants, iron supplements, and folic acid as described in the protocol
Any use of complement inhibitor therapy other than eculizumab in the 12 weeks prior to the screening visit or planned use during the study
Known hypocellular bone marrow based on a history of reduced age-adjusted bone marrow cellularity and/or bone marrow cellularity ≤25%
No documented meningococcal vaccination within 5 years prior to screening visit unless it is documented that vaccination has been administered during the screening period and prior to initiation of study treatment
Unable to take antibiotics for meningococcal prophylaxis, if required by local standard of care
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
Documented positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as described in the protocol
Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
Recent, unstable medical conditions, excluding PNH and PNH-related complications, within the past 3 months prior to screening visit as described in the protocol
Anticipated need for major surgery during the study