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

Phase 3RecruitingNCT07154745

Regeneron Pharmaceuticals35 enrolled

Overview

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 been not well controlled 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)

The treatment period has two parts, a Treatment Period (TP, 28 weeks) and an Extension treatment Period (EP, 52 weeks).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing 2. Currently treated with marketed eculizumab, ravulizumab, or crovalimab at the labeled dose for at least 6 months 3. 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 4. At least 2 screening LDH values from different visits as described in the protocol 5. 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 Exclusion Criteria: 1. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplants 2. Body weight \<40 kilograms at screening visit 3. Patients with a known or suspected C5 mutation that is refractory to their current C5i treatment as described in the protocol 4. Any active or ongoing infection within 2 weeks of screening or during the screening period or any recent infection as described in the protocol 5. Known hereditary complement deficiency Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Outcomes

Primary Outcomes

Percent change in Lactate Dehydrogenase (LDH) during TP

Time frame: From baseline to week 28

Secondary Outcomes

Normalization of LDH

Time frame: Through week 52

Adequate control of hemolysis (LDH ≤1.5 × ULN)

Time frame: Through week 52

Transfusion avoidance

Not requiring a Red Blood Cell (RBC) transfusion as per protocol algorithm based on hemoglobin values

Time frame: Through week 52

Hemoglobin stabilization

Participants who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL

Time frame: Through week 52

Change in hemoglobin from baseline

Time frame: Through week 52

Change in fatigue

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 life

Time frame: Through week 52

Occurrence of all Adverse Events (AEs)

Time frame: Through week 52

Severity of all AEs

Time frame: Through week 52

Occurrence of all Treatment-Emergent Adverse Events (TEAEs)

Time frame: Through week 52

Severity of all TEAEs

Time frame: Through week 52

Change from baseline in Total Complement Hemolytic Activity Assay (CH50)

Time frame: Through week 52

Concentrations of total pozelimab

Time frame: Through week 52

Concentrations of cemdisiran

Time frame: Through week 52

Concentrations of total C5

Time frame: Through week 52

Incidence of Anti-Drug Antibody (ADA) to pozelimab

Time frame: Through week 52

Magnitude of ADA to pozelimab

Time frame: Through week 52

Incidence of ADA to cemdisiran

Time frame: Through week 52

Magnitude of ADA to cemdisiran

Time frame: Through week 52

Percent change in LDH during EP

Time frame: From baseline to week 24 and week 52

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

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts