Myelodysplastic Syndrome Clinical Trial
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
Summary
The primary objective of the study is:
To evaluate the effect on hemolysis and red blood cells (RBC) transfusions over a 24-week treatment period of pozelimab and cemdisiran combination treatment versus ravulizumab treatment in patients with active Paroxysmal Nocturnal Hemoglobinuria (PNH) who are complement inhibitor treatment-naive or have not recently received complement inhibitor therapy
The secondary objectives of the study are to:
Evaluate the effect of pozelimab and cemdisiran combination treatment versus ravulizumab treatment on the following:
Measures of hemolysis
Transfusion parameters
Hemoglobin levels
Fatigue as assessed by Clinical Outcome Assessments (COAs)
Health-related quality of life (HRQoL) as assessed by COAs
Safety and tolerability
Complement activation
To assess the concentrations of total pozelimab and total ravulizumab in serum and total cemdisiran and total complement factor 5 (C5) protein in plasma
To assess the immunogenicity of pozelimab and cemdisiran
Eligibility Criteria
Key Inclusion Criteria:
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 Exclusion Criteria:
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 (when available) 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
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There are 48 Locations for this study
Whittier California, 90603, United States
Toronto Ontario, M5G 2, Canada
Thessaloniki , 570 1, Greece
Budapest , 1089, Hungary
Roma Lazio, 168, Italy
Torino Piemonte, 10126, Italy
Firenze , 50134, Italy
Nagoya Aichi, 466-8, Japan
Ogaki city Gifu, 503-8, Japan
Tsukuba-shi Ibaraki, 305-8, Japan
Moriguchi-city Osaka, 570-8, Japan
Shinagawa-ku Tokyo, 141-8, Japan
Busan , 49241, Korea, Republic of
Gyeonggi-do , 16499, Korea, Republic of
Incheon , 21565, Korea, Republic of
Seoul , 02841, Korea, Republic of
Seoul , 03722, Korea, Republic of
Seoul , 06351, Korea, Republic of
Seoul , 7895, Korea, Republic of
Suwon , 16247, Korea, Republic of
Kuantan Pahang, 25200, Malaysia
Ampang Selangor, 68000, Malaysia
Kota Kinabalu , 88586, Malaysia
Monterrey Nuevo León, 64460, Mexico
Bydgoszcz , 85-16, Poland
Gdansk , 80-21, Poland
Warszawa , 02-77, Poland
Cluj-Napoca Cluj, 40001, Romania
Craiova Dolj, 20014, Romania
Targu Mures Mures, 54013, Romania
Singapore , 11907, Singapore
Bilbao Vizcaya, 48013, Spain
Barcelona , 8036, Spain
Changhua City , 50006, Taiwan
Hualien City , 97002, Taiwan
Kaohsiung , 807, Taiwan
Taichung , 40447, Taiwan
Taipei , 11490, Taiwan
Taoyuan City , 33305, Taiwan
Tapei City , 10022, Taiwan
Ratchathewi Krung Thep Maha Nakhon-Bangkok, 10400, Thailand
Hat Yai Songkhla, 90110, Thailand
Bangkok , 10330, Thailand
Chiang Mai , 50200, Thailand
Khon Kaen , 40000, Thailand
Istanbul , 34418, Turkey
Izmir , 35100, Turkey
Leeds , LS9 7, United Kingdom
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