A Study in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) to Evaluate How Safe Long-term Treatment with Pozelimab + Cemdisiran Combination Therapy is and How Well it Works.
- Conditions
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Registration Number
- 2023-510336-36-00
- Lead Sponsor
- Regeneron Pharmaceuticals Inc.
- Brief Summary
The primary objective of the study is to describe the long-term safety, tolerability, and efficacy of pozelimab + cemdisiran combination therapy in patients with PNH.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised, recruiting
- Sex
- Not specified
- Target Recruitment
- 17
Patients Entering from the Parent Study: 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.
Patients Entering from the Parent Study: Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol
Patients Entering with C5 polymorphism: 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
Patients Entering with C5 polymorphism: Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes
Patients Entering with C5 polymorphism: Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol
Patients Entering with C5 polymorphism: LDH level ≥2 × upper limit of normal (ULN) at the screening visit
Patients Entering with C5 polymorphism: Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol
Patients Entering from the Parent Study: Significant protocol deviation(s) in the parent study based on the investigator’s judgment and to the extent that these would (if continued) impact the study objectives and/or safety of the patient
Patients Entering with C5 polymorphism: 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 Inclusion/ Exclusion Criteria apply
Patients Entering from the Parent Study: 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: 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
Patients Entering with C5 polymorphism: Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
Patients Entering with C5 polymorphism: 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
Patients Entering with C5 polymorphism: Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening
Patients Entering with C5 polymorphism: Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol
Patients Entering with C5 polymorphism: Known hereditary complement deficiency
Patients Entering with C5 polymorphism: Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
Study & Design
- Study Type
- Not specified
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent serious adverse events (SAEs) Incidence of treatment-emergent serious adverse events (SAEs)
Severity of treatment-emergent SAEs Severity of treatment-emergent SAEs
Incidence of treatment emergent adverse events of special interest (AESIs) Incidence of treatment emergent adverse events of special interest (AESIs)
Severity of treatment emergent AESIs Severity of treatment emergent AESIs
Incidence of adverse events (AEs) leading to permanent treatment discontinuation Incidence of adverse events (AEs) leading to permanent treatment discontinuation
Severity 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) Percent change from baseline in lactate dehydrogenase (LDH)
- Secondary Outcome Measures
Name Time Method Maintenance of adequate control of hemolysis (LDH ≤1.5 × ULN) Maintenance of adequate control of hemolysis (LDH ≤1.5 × ULN)
Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis) Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)
Change in fatigue Change in fatigue
Change in physical function (PF) scores on the EORTC QLQ-C30 Change in physical function (PF) scores on the EORTC QLQ-C30
Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30 Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30
Normalization of LDH Normalization of LDH
Rate of red blood cell (RBC) transfusion Rate of red blood cell (RBC) transfusion
Number of units of RBC transfusion Number of units of RBC transfusion
Percentage of days with LDH ≤1.5x upper limit of normal (ULN) Percentage of days with LDH ≤1.5x upper limit of normal (ULN)
Change in hemoglobin levels Change in hemoglobin levels
Change in total complement hemolytic activity assay (CH50) Change in total complement hemolytic activity assay (CH50)
Percent change in CH50 Percent change in CH50
Concentrations of total pozelimab in serum Concentrations of total pozelimab in serum
Concentrations of cemdisiran in plasma Concentrations of cemdisiran in plasma
Incidence of treatment-emergent anti-drug antibodies to pozelimab Incidence of treatment-emergent anti-drug antibodies to pozelimab
Incidence of treatment-emergent anti-drug antibodies to cemdisiran Incidence of treatment-emergent anti-drug antibodies to cemdisiran
Concentration of total complement component 5 (C5) in plasma Concentration of total complement component 5 (C5) in plasma
Percent change of concentration of total C5 in plasma Percent change of concentration of total C5 in plasma
Adequate control of hemolysis (LDH ≤1.5 × ULN) Adequate control of hemolysis (LDH ≤1.5 × ULN)
Transfusion avoidance Transfusion avoidance
Hemoglobin stabilization Hemoglobin stabilization
Percent change in LDH Percent change in LDH
Trial Locations
- Locations (12)
Geniko Nosokomeio Thessalonikis George Papanikolaou
🇬🇷Thessaloniki, Greece
Semmelweis University
🇭🇺Budapest VIII, Hungary
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Rome, Italy
Azienda Ospedaliero Universitaria Careggi
🇮🇹Florence, Italy
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
🇮🇹Turin, Italy
Spitalul Clinic Municipal Filantropia Craiova
🇷🇴Craiova, Romania
Institute Of Oncology Prof. Dr. Ion Chiricuta Cluj-Napoca
🇷🇴Cluj-Napoca, Romania
Spitalul Clinic Judetean De Urgenta Targu Mures
🇷🇴Targu Mures, Romania
Hospital Universitario Basurto
🇪🇸Bilbao, Spain
Hospital Clinic De Barcelona
🇪🇸Barcelona, Spain
Scroll for more (2 remaining)Geniko Nosokomeio Thessalonikis George Papanikolaou🇬🇷Thessaloniki, GreeceChrysavgi LalayanniSite contact+302313307522luizana6@gmail.com