Health Condition 1: D595- Paroxysmal nocturnal hemoglobinuria [Marchiafava-Micheli]
Conditions
Interventions
Intervention1: Cemdisiran: Administered SC per the protocol
Intervention2: Pozelimab: Administered IV and subcutaneous (SC) per the protocol
Control Intervention1: Eculizumab: Administered IV per the
Sponsors
Regeneron Pharmaceuticals, Inc.
PAREXEL International Clinical Research Private Limited
Eligibility
Inclusion criteria
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 greater than or equal to 2 times 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 5. Other protocol-defined Inclusion Criteria apply
Exclusion criteria
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 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 10. Other protocol-defined exclusion Criteria apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Percent change in lactate dehydrogenase (LDH) (Cohort A) - Transfusion avoidance (Cohort B, Not requiring a red blood cell (RBC) transfusion per the protocol) - Adequate control of hemolysis (Cohort B, LDH less than or equal to 1.5 times ULN)Timepoint: - From baseline to week 26 - Post-baseline Day 1 through week 26 - From week 8 through week 26, inclusive | — |
Secondary
| Measure | Time frame |
|---|---|
| Breakthrough hemolysis- LDH greater than or equal to 2 times ULN per the protocolTimepoint: From post-baseline day 1 through week 26;Adequate control of hemolysis-(Cohort A) LDH less than or equal to 1.5 times ULNTimepoint: From week 8 through week 26, inclusive;Hemoglobin stabilization- Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level per the protocolTimepoint: From day 1 (post-baseline) through week 26;Normalization of LDH- LDH less than or equal to 1.0 times ULN per the protocolTimepoint: Between week 8 through week 26, inclusive;Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue ScaleTimepoint: 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)Timepoint: Change from baseline to week 26;Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30Timepoint: From baseline to week 26;Percent change in LDH (Cohort B)Timepoint: From baseline to week 26;Rate of RBC transfusedTimepoint: Post-baseline Day 1 through week 26;Number of units of RBC transfusedTimepoint: Post-baseline Day 1 through week 26;Time to first LDH less than or equal to 1.5 times ULNTimepoint: Up to Week 26;Time to first LDH less than or equal to 1.0 times ULNTimepoint: Up to Week 26;Percentage of days with LDH less than or equal to 1.5 times ULNTimepoint: Between week 8 & week 26, inclusive;Change in hemoglobin levelsTimepoint: From baseline to week 26;Incidence and severity of treatment emergent serious adverse events (SAEs)Timepoint: Up to 26 weeks;Incidence and severity of treatment-emergent adverse events (TEAEs) of special interestTimepoint: Up to 26 weeks;Incidence and severity of TEAEs leading to treatment discontinuationTimepoint: Up to 26 weeks;Change in total CH50Timepoint: From baseline to week 26;Percent change in total CH50Timepoint: From baseline to week 26;Con | — |
Countries
Brazil, Canada, China, Colombia, Greece, Hungary, India, Italy, Japan, Jordan, Malaysia, Mexico, Peru, Philippines, Poland, Republic of Korea, Romania, Singapore, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States of America
Contacts
Public ContactDr Annappa Kamath
PAREXEL International Clinical Research Private Limited
Outcome results
None listed