A Study to Evaluate How Safe Pozelimab + Cemdisiran Combination Therapy is and How Well it Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Not Recently Received or Have Not Received Complement Inhibitor Treatment

Phase 3RecruitingNCT05133531

Regeneron Pharmaceuticals190 enrolled

Overview

This study is researching a clinical treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on people with paroxysmal nocturnal hemoglobinuria (PNH). The aim of the study is to see how safe and effective the pozelimab + cemdisiran combination is for people with PNH and how the combination compares with 2 existing treatments: ravulizumab and eculizumab. The pozelimab + cemdisiran combination may be referred to as "study drugs". Ravulizumab and eculizumab may also be called the "comparator drug". The study is looking at several research questions, including: * How effective is the pozelimab + cemdisiran combination compared to ravulizumab? * How effective is pozelimab + cemdisiran combination compared to eculizumab? * What side effects may happen from taking the study drugs? * How much study drugs are in the blood at different times? * Whether the body makes antibodies against the study drugs (which could make the study drugs less effective or could lead to side effects)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

190

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes as described in the protocol 2. Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms as described in the protocol 3. LDH level ≥2 × ULN at the screening visit 4. 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 Key Exclusion Criteria: 1. Prior treatment with eculizumab within 3 months prior to screening, ravulizumab within 6 months prior to screening, or other complement inhibitors within 5 half-lives of the respective agent prior to screening 2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant 3. Body weight \<40 kilograms at screening visit 4. Planned use of any complement inhibitor therapy other than study drugs during the treatment period 5. Not meeting meningococcal vaccination requirements and, at a minimum documentation of quadrivalent meningococcal vaccination within 5 years prior to the screening visit and serotype B vaccine within 3 years prior to the screening visit as described in the protocol. 6. Any contraindication for receiving Neisseria meningitidis vaccinations (serotypes ACWY and B). 7. Unable to take antibiotics for meningococcal prophylaxis (if required by local ravulizumab \[Cohort A\] or eculizumab \[Cohort B\] prescribing information, where available, or national guidelines/local practice, or if necessary when administration of the first dose of the quadrivalent meningococcal vaccine \[serotype ACWY\] or the second dose of the serotype B meningococcal vaccine \[when available\] is less than 2 weeks prior to study treatment initiation) as described in the protocol 8. 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 9. Documented history of active, uncontrolled, ongoing systemic autoimmune diseases Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Locations (69)

The Oncology Institute of Hope & Innovation

Whittier, California, United States

RECRUITING

Centro de Estudos e Pesquisas em Hematologia e Oncologia

Santo André, São Paulo, Brazil

RECRUITING

A Beneficencia Portuguesa de Sao Paulo, BP Mirante

São Paulo, Brazil

RECRUITING

Casa de Saude Santa Marcelina

São Paulo, Brazil

Outcomes

Primary Outcomes

Percent change in lactate dehydrogenase (LDH)

Cohort A

Time frame: From baseline to week 26

Transfusion avoidance

Cohort B Not requiring a red blood cell (RBC) transfusion per the protocol

Time frame: From post-baseline day 1 through week 26

Adequate control of hemolysis

Cohort B LDH ≤1.5 × ULN at each visit

Time frame: From week 8 through week 26, inclusive

Secondary Outcomes

Maintenance of adequate control of hemolysis

Cohort A and B LDH ≤1.5 × ULN

Time frame: From week 8 through week 26, inclusive

Breakthrough hemolysis

Cohort A and B LDH ≥2 × ULN per the protocol

Time frame: From post-baseline day 1 through week 26

Adequate control of hemolysis

Cohort A LDH ≤1.5 × ULN

Time frame: From week 8 through week 26, inclusive

Hemoglobin stabilization

Cohort A and B Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level per the protocol

Time frame: From day 1 (post-baseline) through week 26

Normalization of LDH

Cohort A and B LDH ≤1.0 × ULN per the protocol

Time frame: Between week 8 through week 26, inclusive

Transfusion avoidance

Cohort A Not requiring an RBC transfusion as per protocol algorithm based on post-baseline hemoglobin values.

Time frame: Day 1 through week 26

Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale

Cohort A and B FACIT-Fatigue Scale is a 13-item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related quality of life (QoL) in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.

Time frame: From baseline to week 26

Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)

Cohort A and B EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 7 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, sleep and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."

Time frame: From baseline to week 26

Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30

Time frame: From baseline to week 26

Percent change in LDH

Cohort B

Time frame: From baseline to week 26

Rate of RBC transfused

Cohort A and B Per protocol algorithm

Time frame: Post-baseline Day 1 through week 26

Number of units of RBC transfused

Cohort A and B Per protocol algorithm

Time frame: Post-baseline Day 1 through week 26

Time to first LDH ≤1.5 × ULN

Cohort A and B

Time frame: Up to Week 26

Time to first LDH ≤1.0 × ULN

Cohort A and B

Time frame: Up to Week 26

Percentage of days with LDH ≤1.5 × ULN

Cohort A and B

Time frame: Between week 8 and week 26, inclusive

Change in hemoglobin levels

Cohort A and B

Time frame: From baseline to week 26

Incidence and severity of treatment emergent serious adverse events (SAEs)

Cohort A and B

Time frame: Up to 26 weeks

Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest

Cohort A and B

Time frame: Up to 26 weeks

Incidence and severity of TEAEs leading to treatment discontinuation

Cohort A and B

Time frame: Up to 26 weeks

Change in total CH50

Cohort A and B

Time frame: From baseline to week 26

Percent change in total CH50

Cohort A and B

Time frame: From baseline to week 26

Concentration of total C5 in plasma

Cohort A and B

Time frame: Up to 60 weeks

Concentrations of total pozelimab in serum

Cohort A and B

Time frame: Up to 60 weeks

Concentrations of cemdisiran in plasma

Cohort A and B

Time frame: Up to 60 weeks

Concentrations of total ravulizumab in serum

Cohort A

Time frame: Up to 34 weeks

Concentrations of total eculizumab in serum

Cohort B

Time frame: Up to 30 weeks

Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab

Cohort A and B

Time frame: Up to 60 weeks

Incidence of treatment emergent ADAs to cemdisiran

Cohort A and B

Time frame: Up to 60 weeks

A Study to Evaluate How Safe Pozelimab + Cemdisiran Combination Therapy is and How Well it Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have Not Recently Received or Have Not Received Complement Inhibitor Treatment

Overview

Conditions

Interventions

Eligibility

Locations (69)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts