Paroxysmal Nocturnal Hemoglobinuria
Conditions
Keywords
PNH
Brief summary
This study is researching a clinical treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on people with paroxysmal nocturnal hemoglobinuria (PNH). The aim of the study is to see how safe and effective the pozelimab + cemdisiran combination is for people with PNH and how the combination compares with 2 existing treatments: ravulizumab and eculizumab. The pozelimab + cemdisiran combination may be referred to as "study drugs". Ravulizumab and eculizumab may also be called the "comparator drug". The study is looking at several research questions, including: * How effective is the pozelimab + cemdisiran combination compared to ravulizumab? * How effective is pozelimab + cemdisiran combination compared to eculizumab? * What side effects may happen from taking the study drugs? * How much study drugs are in the blood at different times? * Whether the body makes antibodies against the study drugs (which could make the study drugs less effective or could lead to side effects)
Interventions
DRUGRavulizumab
Administered Intravenous (IV) per the protocol
DRUGPozelimab
Administered IV and subcutaneous (SC) per the protocol
DRUGCemdisiran
Administered SC per the protocol
DRUGEculizumab
Administered IV per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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 ≥2 × 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 Key
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 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 Note: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent change in lactate dehydrogenase (LDH) | From baseline to week 26 | Cohort A |
| Transfusion avoidance | From post-baseline day 1 through week 26 | Cohort B Not requiring a red blood cell (RBC) transfusion per the protocol |
| Adequate control of hemolysis | From week 8 through week 26, inclusive | Cohort B LDH ≤1.5 × ULN at each visit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance of adequate control of hemolysis | From week 8 through week 26, inclusive | Cohort A and B LDH ≤1.5 × ULN |
| Breakthrough hemolysis | From post-baseline day 1 through week 26 | Cohort A and B LDH ≥2 × ULN per the protocol |
| Adequate control of hemolysis | From week 8 through week 26, inclusive | Cohort A LDH ≤1.5 × ULN |
| Hemoglobin stabilization | From day 1 (post-baseline) through week 26 | Cohort A and B Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level per the protocol |
| Normalization of LDH | Between week 8 through week 26, inclusive | Cohort A and B LDH ≤1.0 × ULN per the protocol |
| Transfusion avoidance | Day 1 through week 26 | Cohort A Not requiring an RBC transfusion as per protocol algorithm based on post-baseline hemoglobin values. |
| Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale | From baseline to week 26 | Cohort A and B FACIT-Fatigue Scale 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 quality of life (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 greater fatigue. |
| Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) | From baseline to week 26 | Cohort A and B EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 7 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, sleep and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much." |
| Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30 | From baseline to week 26 | Cohort A and B EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 7 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, sleep and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much." |
| Percent change in LDH | From baseline to week 26 | Cohort B |
| Rate of RBC transfused | Post-baseline Day 1 through week 26 | Cohort A and B Per protocol algorithm |
| Number of units of RBC transfused | Post-baseline Day 1 through week 26 | Cohort A and B Per protocol algorithm |
| Time to first LDH ≤1.5 × ULN | Up to Week 26 | Cohort A and B |
| Time to first LDH ≤1.0 × ULN | Up to Week 26 | Cohort A and B |
| Percentage of days with LDH ≤1.5 × ULN | Between week 8 and week 26, inclusive | Cohort A and B |
| Change in hemoglobin levels | From baseline to week 26 | Cohort A and B |
| Incidence and severity of treatment emergent serious adverse events (SAEs) | Up to 26 weeks | Cohort A and B |
| Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest | Up to 26 weeks | Cohort A and B |
| Incidence and severity of TEAEs leading to treatment discontinuation | Up to 26 weeks | Cohort A and B |
| Change in total CH50 | From baseline to week 26 | Cohort A and B |
| Percent change in total CH50 | From baseline to week 26 | Cohort A and B |
| Concentration of total C5 in plasma | Up to 60 weeks | Cohort A and B |
| Concentrations of total pozelimab in serum | Up to 60 weeks | Cohort A and B |
| Concentrations of cemdisiran in plasma | Up to 60 weeks | Cohort A and B |
| Concentrations of total ravulizumab in serum | Up to 34 weeks | Cohort A |
| Concentrations of total eculizumab in serum | Up to 30 weeks | Cohort B |
| Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab | Up to 60 weeks | Cohort A and B |
| Incidence of treatment emergent ADAs to cemdisiran | Up to 60 weeks | Cohort A and B |
Countries
Brazil, Canada, China, Colombia, Greece, Hungary, India, Italy, Japan, Jordan, Malaysia, Mexico, Peru, Philippines, Poland, Romania, Singapore, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed