A Study to Evaluate How Pozelimab + Cemdisiran Combination Therapy Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Whose Current Treatment is Not Working Efficiently
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Interventions
- Registration Number
- NCT07154745
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
This study is researching a treatment combination with two experimental drugs called pozelimab and cemdisiran referred to as "study drugs". Researchers are looking for a better way to treat Paroxysmal Nocturnal Hemoglobinuria (PNH).
The aim of the study is to see how well the pozelimab and cemdisiran combination works to lower hemolysis in participants whose PNH has not gotten better even after taking other complement component 5 (C5) inhibitors, eculizumab/eculizumab biosimilar, ravulizumab or crovalimab.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drugs?
* How much of the study drugs are in the blood at different times?
* Whether the body makes antibodies against the study drug (which could make the study drugs not work as well or could lead to side effects)
- Detailed Description
The treatment period has two parts, a Treatment Period (TP, 28 weeks) and an Extension treatment Period (EP, 52 weeks).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 35
- Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
- Currently treated with marketed eculizumab, ravulizumab, or crovalimab at the labeled dose for at least 6 months
- LDH persistently > 1.5 × Upper limit of normal (ULN) in the previous 6 months that the Principal Investigator (PI) attributes is due to intravascular hemolysis
- At least 2 screening LDH values from different visits as described in the protocol
- Willing and able to comply with clinic/remote visits and study-related procedures, including completion of the full series of meningococcal vaccinations required per protocol and agreement to continue to remain up to date with these vaccinations during the study
Key
- Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplants
- Body weight <40 kilograms at screening visit
- Patients with a known or suspected C5 mutation that is refractory to their current C5i treatment as described in the protocol
- Any active or ongoing infection within 2 weeks of screening or during the screening period or any recent infection as described in the protocol
- Known hereditary complement deficiency
Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pozelimab + Cemdisiran Combo Pozelimab - Pozelimab + Cemdisiran Combo Cemdisiran -
- Primary Outcome Measures
Name Time Method Percent change in Lactate Dehydrogenase (LDH) during TP From baseline to week 28
- Secondary Outcome Measures
Name Time Method Normalization of LDH Through week 52 Change in fatigue Through week 52 As measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale.
The FACIT-Fatigue assesses the level of fatigue using a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating a higher quality of lifeOccurrence of all Adverse events (AEs) Through week 52 Adequate control of hemolysis (LDH ≤1.5 × ULN) Through week 52 Transfusion avoidance Through week 52 Not requiring a Red Blood Cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Change in hemoglobin from baseline Through week 52 Concentrations of total C5 Through week 52 Hemoglobin stabilization Through week 52 Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Concentrations of total pozelimab Through week 52 Concentrations of cemdisiran Through week 52 Incidence of anti-drug antibody (ADA) to pozelimab Through week 52 Titer of ADA to pozelimab Through week 52 Incidence of ADA to cemdisiran Through week 52 Titer of ADA to cemdisiran Through week 52 Percent change in LDH during EP From baseline to week 24 and week 52 Severity of all AEs Through week 52 Occurrence of all Treatment-Emergent Adverse Events (TEAEs) Through week 52 Severity of all TEAEs Through week 52 Change from baseline in Total Complement Hemolytic Activity Assay (CH50) Through week 52