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 patients with paroxysmal nocturnal hemoglobinuria (PNH). The aim of the study is to see how safe and effective the pozelimab + cemdisiran combination is for patients with PNH and how the combination compares with 2 existing treatments, one called ravulizumab and the other called 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 vaccination is less than 2 weeks prior to study treatment initiation)
- 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
Transfusion avoidance From post-baseline day 1 through week 26 Cohort B Not requiring a red blood cell (RBC) transfusion per the protocol
Maintenance of adequate control of hemolysis From week 8 through week 26, inclusive Cohort B LDH ≤1.5 × ULN
- Secondary Outcome Measures
Name Time Method Maintenance of adequate control of hemolysis From week 8 through week 26, inclusive Cohort A LDH ≤1.5 × ULN
Transfusion avoidance Day 1 through week 26 Cohort A Not requiring an RBC transfusion as per protocol algorithm based on post-baseline hemoglobin values.
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
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 and B LDH ≤1.5 × ULN
Normalization of LDH Between week 8 through week 26, inclusive Cohort A and B LDH ≤1.0 × ULN per the protocol
Percent change in LDH From baseline to week 26 Cohort B
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.
Number of units of RBC transfused Post-baseline Day 1 through week 26 Cohort A and B Per protocol algorithm
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
Rate of RBC transfused Post-baseline Day 1 through week 26 Cohort A and B Per protocol algorithm
Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Change 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."
Change in hemoglobin levels From baseline 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
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
Incidence and severity of treatment emergent serious adverse events (SAEs) Up to 26 weeks Cohort A and B
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
Trial Locations
- Locations (58)
Clinica San Felipe
🇵🇪Lima, Peru
St Lukes Medical Center
🇵🇭Quezon City, Central Luzon, Philippines
Taichung Veterans General Hospital (VGHTC)
🇨🇳Taichung City, Taiwan
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
George Papanikolaou Hospital
🇬🇷Thessaloniki, Greece
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Rajiv Gandhi Cancer Institute and Research Centre
🇮🇳New Delhi, Delhi, India
Malabar Cancer Centre
🇮🇳Kannur, Kerala, India
Amrita Institute of Medical Sciences (AIMS) and Research Centre
🇮🇳Kochi, Kerala, India
Bhagwan Mahaveer Cancer Hospital & Research Centre
🇮🇳Jaipur, Rajasthan, India
Kings George's Medical University
🇮🇳Lucknow, Uttar Pradesh, India
Postgraduate Institute of Medical Education and Research
🇮🇳Chandigarh, India
Fondazione Policlinico Universitario A Gemelli
🇮🇹Roma, Lazio, Italy
Azienda Ospedaliera Città della Salute e della Scienza di Torino
🇮🇹Torino, Piemonte, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
🇯🇵Nagoya, Aichi, Japan
Ogaki Municipal Hospital
🇯🇵Ogaki city, Gifu, Japan
University of Tsukuba Hospital
🇯🇵Tsukuba-shi, Ibaraki, Japan
Panasonic Health Insurance Organization Matsushita Memorial Hospital
🇯🇵Moriguchi-city, Osaka, Japan
NTT Medical Center Tokyo
🇯🇵Shinagawa-ku, Tokyo, Japan
University of Jordan
🇯🇴Amman, Jordan
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Ajou University Medical Center
🇰🇷Gyeonggi-do, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Korea University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center - PPDS
🇰🇷Seoul, Korea, Republic of
Ewha Womans University Mokdong Hospital
🇰🇷Seoul, Korea, Republic of
St. Vincent Hospital
🇰🇷Suwon, Korea, Republic of
Hospital Tengku Ampuan Afzan
🇲🇾Kuantan, Pahang, Malaysia
Hospital Ampang
🇲🇾Ampang, Selangor, Malaysia
Queen Elizabeth Hospital - Kota Kinabalu
🇲🇾Kota Kinabalu, Malaysia
Hospital Universitario Dr. Jose Eleuterio González
🇲🇽Monterrey, Nuevo León, Mexico
Klinika Hematologii, Szpital Uniwersytecki Nr 2 im. Jana Biziela w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Instytut Hematologii i Transfuzjologii
🇵🇱Warszawa, Poland
Prof Dr I Chiricuta Institute of Oncology
🇷🇴Cluj-Napoca, Cluj, Romania
Filantropia Municipal Clinical Hospital
🇷🇴Craiova, Dolj, Romania
Targu-Mures Emergency Clinical County Hospital
🇷🇴Targu Mures, Mures, Romania
National University Hospital
🇸🇬Singapore, Singapore
Hospital Universitario Basurto
🇪🇸Bilbao, Vizcaya, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Changhua Christian Hospital
🇨🇳Changhua City, Taiwan
Hualien Tzu Chi Hospital
🇨🇳Hualien City, Taiwan
Kaohsiung Medical University - Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital - PPDS
🇨🇳Taichung, Taiwan
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Chang Gung Hospital
🇨🇳Taoyuan City, Taiwan
National Taiwan University Hospital
🇨🇳Tapei City, Taiwan
Rajavithi Hospital
🇹🇭Ratchathewi, Krung Thep Maha Nakhon-Bangkok, Thailand
Songklanagarind Hospital Prince of Songkla University
🇹🇭Hat Yai, Songkhla, Thailand
King Chulalongkorn Memorial Hospital
🇹🇭Bangkok, Thailand
Chiang Mai University
🇹🇭Chiang Mai, Thailand
Srinagarind Hospital
🇹🇭Khon Kaen, Thailand
Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi
🇹🇷Istanbul, Turkey
Ege Universitesi Tip Fakultesi Hastanesi
🇹🇷Izmir, Turkey
St James University Hospital
🇬🇧Leeds, United Kingdom
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