Paroxysmal Nocturnal Hemoglobinuria
Conditions
Interventions
Pozelimab and Cemdisiran Combination:
Drug: Pozelimab
SC Q4W
Other names: REGN3918
Drug: Cemdisiran
SC Q4W
Other names: ALN-CC5
Administered SC per the protocol
The duration of the OLEP for a pat
Sponsors
Taneja Deepak
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients Entering from the Parent Study 1. Patients with PNH who have completed, without permanent discontinuation, study treatment in the parent study (R3918-PNH-2021 [NCT05133531]), including the post-Open-label treatment period (OLTP) transition period, if applicable. 2. Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol. Patients Entering with C5 polymorphism 1. Patients with PNH who have a documented C5 polymorphism rendering them refractory to eculizumab or ravulizumab (eg, p.Arg885His, p.Arg885Cys), as described in the protocol 2. Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes 3. Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol 4. LDH level >= 2 x upper limit of normal (ULN) at the screening visit 5. Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol Note: Other protocol-defined Inclusion Criteria apply.
Exclusion criteria
Exclusion criteria: Patients Entering from the Parent Study: 1. Significant protocol deviation(s) in the parent study based on the investigators judgment and to the extent that these would (if continued) impact the study objectives and/or safety of the patient 2. Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in or completing the study Patients Entering with C5 polymorphism: 1. Prior treatment with complement inhibitors within 5 half-lives of the respective agent prior to screening, except for prior eculizumab or ravulizumab which are not exclusionary 2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant 3. Not meeting meningococcal vaccination requirements and, at a minimum, documentation of quadrivalent meningococcal vaccination within 5 years prior to enrollment and serotype B vaccine within 3 years prior to enrollment as described in the protocol 4. Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening 5. Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol 6. Known hereditary complement deficiency 7. Documented history of active, uncontrolled, ongoing systemic autoimmune diseases 8. Documented history of liver cirrhosis or patients with liver disease with evidence of current impaired liver function or patients with elevations in Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) (unrelated to PNH or its complications) as described in the protocol Note: Other protocol-defined Exclusion Criteria apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Incidence of treatment-emergent serious adverse events (SAEs) - Severity of treatment-emergent SAEs - Incidence of treatment emergent adverse events of special interest (AESIs) - Severity of treatment emergent AESIs - Incidence of adverse events (AEs) leading to permanent treatment discontinuation - Severity of adverse events (AEs) leading to permanent treatment discontinuation - Percent change from baseline in lactate dehydrogenase (LDH) | — |
Secondary
| Measure | Time frame |
|---|---|
| - Maintenance of adequate control of hemolysis (LDH =2 x ULN [subsequent to initial achievement of LDH <=1.5 x ULN] concomitant with signs or symptoms associated with hemolysis) - Hemoglobin stabilization - Percent change in LDH - Change in fatigue - Change in physical function (PF) scores on the EORTC QLQ-C30 - Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30 - Normalization of LDH - Rate of red blood cell (RBC) transfusion - Number of units of RBC transfusion - Percentage of days with LDH <=1.5 x upper limit of normal (ULN) - Change in hemoglobin levels - Change in total complement hemolytic activity assay (CH50) - Percent change in CH50 - Concentrations of total pozelimab in serum - Concentrations of cemdisiran in plasma - Incidence of treatment-emergent anti-drug antibodies to pozelimab - Incidence of treatment-emergent anti-drug antibodies to cemdisiran - Concentration of total complement component 5 (C5) in plasma - Percent change of concentration of total C5 in plasma | — |
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