Paroxysmal Nocturnal Hemoglobinuria
Conditions
Interventions
Cohort A:
Ravulizumab Arm:
-Drug: Ravulizumab
Administered Intravenous (IV) per the protocol
Other Names: ALXN1210, Ultomiris
Pozelimab + Cemdisiran Arm:
-Drug: Pozelimab
Administered IV and subc
Sponsors
Taneja Deepak
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes described in the protocol 2. Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol 3. LDH level >=2xULN 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 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 <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 vaccination (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 vaccination is less than 2 weeks prior to study treatment initiation). 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 Exclusion Criteria Apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cohort A: Percent change in lactate dehydrogenase (LDH) Cohort B: 1. Maintenance of adequate control of hemolysis 2. Transfusion avoidance | — |
Secondary
| Measure | Time frame |
|---|---|
| Cohort A and B (unless otherwise indicated ): 1. Maintenance of adequate control of hemolysis (defined as LDH =2xULN) 3. Adequate control of hemolysis (defined as LDH =2 g/dL) 5. Normalization of LDH 6. Transfusion Avoidance [Cohort A] 7. Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT)-Fatigue Scale 8. Change in physical function (PF) scores on the European Or-ganisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) 9. Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30 10. Percent change in LDH [Cohort B] 11. Rate of RBC transfused per protocol algorithm 12. Number of units of RBC transfused per protocol algorithm 13. Time to first LDH <=1.5xULN 14. Time to first LDH <=1.0xULN 15. Percentage of days with LDH <=1.5xULN 16. Change in hemoglobin levels 17. Incidence and severity of treatment emergent serious adverse events (SAEs) 18. Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest 19. Incidence and severity of TEAE leading to treatment discon-tinuation 20. Change in total CH50 21. Percent change in total CH50 22. Concentration of total C5 in plasma 23. Concentrations of total pozelimab in serum 24. Concentrations of cemdisiran in plasma 25. Concentrations of total ravulizumab in serum[Cohort A] 26. Concentrations of total eculizumab in serum [Cohort B] 27. Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab 28. Incidence of treatment emergent ADAs to cemdisiran | — |
Countries
Canada, China, Colombia, France, Greece, Hungary, India, Italy, Japan, Jordan, Malaysia, Mexico, Peru, Philippines, Poland, Romania, Singapore, South Africa, South Korea, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactChikako Rosario
Parexel International Inc.
Outcome results
None listed