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
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Interventions
- Registration Number
- NCT05133531
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 190
- Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes as described in the protocol
- Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms as described in the protocol
- LDH level ≥2 × ULN at the screening visit
- 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
- 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
- Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
- Body weight <40 kilograms at screening visit
- Planned use of any complement inhibitor therapy other than study drugs during the treatment period
- 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.
- Any contraindication for receiving Neisseria meningitidis vaccinations (serotypes ACWY and B).
- 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
- 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 history of active, uncontrolled, ongoing systemic autoimmune diseases
Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A Ravulizumab Randomized 1:1 Cohort A Pozelimab Randomized 1:1 Cohort A Cemdisiran Randomized 1:1 Cohort B Pozelimab Randomized 1:1 Cohort B Cemdisiran Randomized 1:1 Cohort B Eculizumab Randomized 1:1
- Primary Outcome Measures
Name Time Method Percent change in lactate dehydrogenase (LDH) From baseline to week 26 Cohort A
Adequate control of hemolysis From week 8 through week 26, inclusive Cohort B LDH ≤1.5 × ULN at each visit
Transfusion avoidance From post-baseline day 1 through week 26 Cohort B Not requiring a red blood cell (RBC) transfusion per the protocol
- Secondary Outcome Measures
Name Time Method Maintenance of adequate control of hemolysis From week 8 through week 26, inclusive Cohort A and B LDH ≤1.5 × ULN
Breakthrough hemolysis From post-baseline day 1 through week 26 Cohort A and B LDH ≥2 × ULN per the protocol
Adequate control of hemolysis From week 8 through week 26, inclusive Cohort A LDH ≤1.5 × ULN
Hemoglobin stabilization From day 1 (post-baseline) through week 26 Cohort A and B Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level per the protocol
Normalization of LDH Between week 8 through week 26, inclusive Cohort A and B LDH ≤1.0 × ULN per the protocol
Transfusion avoidance Day 1 through week 26 Cohort A Not requiring an RBC transfusion as per protocol algorithm based on post-baseline hemoglobin values.
Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale From baseline to week 26 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.
Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) From baseline to week 26 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."
Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30 From baseline to week 26 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 to first LDH ≤1.5 × ULN Up to Week 26 Cohort A and B
Time to first LDH ≤1.0 × ULN Up to Week 26 Cohort A and B
Percentage of days with LDH ≤1.5 × ULN Between week 8 and week 26, inclusive Cohort A and B
Change in hemoglobin levels From baseline to week 26 Cohort A and B
Incidence and severity of treatment emergent serious adverse events (SAEs) Up to 26 weeks Cohort A and B
Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest Up to 26 weeks Cohort A and B
Incidence and severity of TEAEs leading to treatment discontinuation Up to 26 weeks Cohort A and B
Change in total CH50 From baseline to week 26 Cohort A and B
Percent change in total CH50 From baseline to week 26 Cohort A and B
Concentration of total C5 in plasma Up to 60 weeks Cohort A and B
Concentrations of total pozelimab in serum Up to 60 weeks Cohort A and B
Concentrations of cemdisiran in plasma Up to 60 weeks Cohort A and B
Concentrations of total ravulizumab in serum Up to 34 weeks Cohort A
Concentrations of total eculizumab in serum Up to 30 weeks Cohort B
Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab Up to 60 weeks Cohort A and B
Incidence of treatment emergent ADAs to cemdisiran Up to 60 weeks Cohort A and B
Percent change in LDH From baseline to week 26 Cohort B
Rate of RBC transfused Post-baseline Day 1 through week 26 Cohort A and B Per protocol algorithm
Number of units of RBC transfused Post-baseline Day 1 through week 26 Cohort A and B Per protocol algorithm
Trial Locations
- Locations (63)
The Oncology Institute of Hope & Innovation
🇺🇸Whittier, California, United States
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Hospital Pablo Tobon Uribe
🇨🇴Medellin, Antioquia, Colombia
George Papanikolaou Hospital
🇬🇷Thessaloniki, Greece
Semmelweis University
🇭🇺Budapest, Hungary
Rajiv Gandhi Cancer Institute & Research Center (RGCIRC) - Rohini Campus
🇮🇳New Delhi, Delhi, India
Malabar Cancer Center, Kerala
🇮🇳Kannur, Kerala, India
Amrita Institute of Medical Sciences (AIMS) and Research Centre Aims
🇮🇳Kochi, Kerala, India
K J Somaiya Super Specialty Hospital & Research Centre
🇮🇳Mumbai, Maharashtra, India
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