Pozelimab and Cemdisiran Combination Therapy in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Switch From Eculizumab Therapy
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Interventions
- Registration Number
- NCT04888507
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
The primary objective of the study is to evaluate the safety and tolerability of pozelimab and cemdisiran combination therapy in participants with PNH who switch from eculizumab therapy
The secondary objectives of the study are:
* To evaluate the effect of the combination treatment on the following parameters of intravascular hemolysis: lactate dehydrogenase (LDH) control, breakthrough hemolysis, and inhibition of CH50
* To evaluate the effect of the combination treatment on the stability of LDH during the transition period from eculizumab monotherapy to combination with pozelimab and cemdisiran
* To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements
* To evaluate the effect of the combination treatment on hemoglobin levels
* To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life (HRQoL)
* To assess the concentrations of total pozelimab and eculizumab in serum; and total cemdisiran and C5 protein in plasma
* To assess the immunogenicity of pozelimab and cemdisiran
* To assess safety after dose intensification
* To evaluate the long-term safety and efficacy of the combination treatment in an optional open-label extension period (OLEP)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 6
- Diagnosis of paroxysmal nocturnal hemoglobinuria confirmed by a history of high-sensitivity flow cytometry from prior testing
- Treated with stable (ie, no change in dose or frequency) eculizumab therapy at the labeled dosing regimen or a higher dose and/or more frequently administered than labeled for at least 12 weeks prior to screening visit
Key
- History of bone marrow transplantation or receipt of an organ transplant
- Body weight <40 kg at screening
- Current plans for modification of the following background concomitant medications, as applicable, during screening and treatment period: erythropoietin, immunosuppressive drugs, corticosteroids, anti-thrombotic agents, anticoagulants, iron supplements, and folic acid as described in the protocol
- Any use of complement inhibitor therapy other than eculizumab in the 12 weeks prior to the screening visit or planned use during the study
- Known hypocellular bone marrow based on a history of reduced age-adjusted bone marrow cellularity and/or bone marrow cellularity ≤25%
- No documented meningococcal vaccination within 5 years prior to screening visit unless it is documented that vaccination has been administered during the screening period and prior to initiation of study treatment
- Unable to take antibiotics for meningococcal prophylaxis, if required by local standard of care
- 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 positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as described in the protocol
- Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
- Recent, unstable medical conditions, excluding PNH and PNH-related complications, within the past 3 months prior to screening visit as described in the protocol
- Anticipated need for major surgery during the study
NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pozelimab+Cemdisiran Cemdisiran - Pozelimab+Cemdisiran Pozelimab -
- Primary Outcome Measures
Name Time Method Incidence and severity of treatment emergent adverse events (TEAEs) Through day 225 Open Label Treatment Period (OLTP)
- Secondary Outcome Measures
Name Time Method Change from baseline in concentration of total C5 Up to Day 225 OLTP
Number of units of RBCs transfused Day 1 through Week 52 OLEP
Proportion of participants who maintain adequate control of hemolysis Day 57 through Day 225 OLTP
Incidence and severity of TEAEs in participants treated with pozelimab and cemdisiran combination therapy Through Week 52 Optional Open-Label Extension Period (OLEP)
Change of LDH Day 1 to Week 52 OLEP
Proportion of participants who maintain adequate control of their hemolysis Day 1 through Week 52 OLEP
Proportion of participants with normalization of LDH at each visit Day 1 through Week 52 OLEP
Change in fatigue as measured by FACIT-Fatigue scale Day 1 to Week 52 OLEP
Concentrations of total pozelimab in serum Up to Week 52 OLEP
Concentrations of total C5 Up to Week 52 OLEP
Concentrations of cemdisiran in plasma Up to Week 52 OLEP
Percent change in LDH from pre-treatment to end-of-treatment period Screening through Day 225 OLTP
Percent change in LDH from pre-treatment Screening through Day 29 OLTP
Proportion of participants who are transfusion-free Day 1 through Week 52 OLEP Not requiring an RBC transfusion as per protocol algorithm
Rate of RBCs transfused Day 1 through Week 52 OLEP
Proportion of participants with breakthrough hemolysis Day 1 through Week 52 OLEP
Proportion of participants with adequate control of hemolysis at each visit Day 1 through Week 52 OLEP
Proportion of participants with normalization of their LDH at each visit Post Baseline (on Day 1) through Day 225 OLTP
Area under the curve (AUC) of LDH over time Baseline through Day 225 OLTP
AUC of LDH over time Day 1 through Week 52 OLEP
Proportion of participants with hemoglobin stabilization Day 1 through Week 52 OLEP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels meeting pre-specified criteria.
Change in hemoglobin levels Day 1 to Week 52 OLEP
Change in fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale Baseline to Day 225 OLTP The FACIT-Fatigue is a 13-item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating a higher quality of life.
Change in health related quality of life (HRQoL) as measured by the global health status subscale of the European Organization for Research and Treatment of Cancer (EORTC)- Quality of Life Cancer Patients Questionnaire (QLQ) - 30 Scale Baseline to Day 225 OLTP EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small. A change of 10 - 20 points is considered a moderate change.
Change in physical function (PF) scores on the EORTC QLQ-C30 Baseline to Day 225 OLTP
Change in total CH50 Baseline to Day 225 OLTP
Concentrations of total pozelimab and eculizumab in serum Up to Day 225 OLTP
Concentrations of total cemdisiran in plasma Up to Day 225 OLTP
Incidence of pozelimab anti-drug antibody (ADA) responses over time Up to Week 52 OLEP
Incidence of cemdisiran anti-drug antibody (ADA) responses over time Up to Week 52 OLEP
Incidence and severity of TEAEs for participants who receive dose intensification Through Day 225 Intensified OLTP
Percent change of LDH Day 1 to Week 52 OLEP
Change in GHS/QoL on the EORTC QLQ-C30 Day 1 to Week 52 OLEP
Change in PF scores on the EORTC QLQ-C30 Day 1 to Week 52 OLEP
Change in CH50 Day 1 to Week 52 OLEP
Trial Locations
- Locations (1)
Regeneron Study Site
🇬🇧Leeds, United Kingdom