Clinical trial NCT05131204: Efficacy and Safety of the Combination of Pozelimab and Cemdisiran Versus Continued Eculizumab or Ravulizumab Treatment in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria
Official title: A Randomized, Open-Label, Eculizumab and Ravulizumab Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Are Currently Treated With Eculizumab or Ravulizumab
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: PNH
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-11-23
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is:

To evaluate the effect of pozelimab and cemdisiran combination therapy on hemolysis, as assessed by lactate dehydrogenase (LDH), after 36 weeks of treatment, in patients with PNH who switch from eculizumab or ravulizumab therapy versus patients who continue their eculizumab or ravulizumab therapy

The secondary objectives of the study are to:

* Evaluate the effect of pozelimab and cemdisiran combination treatment versus anti-C5 standard-of-care treatment (eculizumab or ravulizumab) on the following:

  * Transfusion requirements and transfusion parameters
  * Measures of hemolysis: LDH control, breakthrough hemolysis, and inhibition of CH50
  * Hemoglobin levels
  * Fatigue as assessed by Clinical Outcome Assessments (COAs)
  * Health-related quality of life (HRQoL) as assessed by COAs
  * Safety and tolerability
* To assess the concentrations of total pozelimab and either total eculizumab or total ravulizumab in serum and total cemdisiran and total C5 protein in plasma
* To assess the immunogenicity of pozelimab and cemdisiran


Eligibility criteria: Key Inclusion Criteria:

1. Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
2. Treated with eculizumab or ravulizumab prior to screening visit as described in the protocol Note: Biosimilars are not permitted, unless approved by the Sponsor

Key Exclusion Criteria:

1. Patients with a screening LDH \>1.5 × ULN who have not taken their C5 inhibitor within the labeled dose interval at the dose prior to the screening LDH assessment
2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
3. Body weight \< 40 kilograms at screening visit
4. Any use of complement inhibitor therapy other than eculizumab or ravulizumab in the 26 weeks prior to the screening visit or planned use during the study with the exception of study treatments
5. Not meeting meningococcal vaccination requirements for eculizumab or ravulizumab according to the current local prescribing information (where available) and at a minimum documentation of meningococcal vaccination within 5 years prior to screening visit.
6. Any contraindication for receiving Neisseria meningitidis vaccination.
7. Positive for hepatitis B, and/ or hepatitis C as described in the protocol
8. History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
9. Participation in another interventional clinical study (except R3918-PNH-2021) or use of any experimental therapy within 30 days before screening visit or within 5 half-lives of that investigational product, whichever is greater, with the exception of eculizumab or ravulizumab.
10. Patients with functional or anatomic asplenia

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Primary outcomes:
measure: Percent Change in Lactate Dehydrogenase (LDH) From Baseline to Week 36
timeFrame: From baseline to week 36
Secondary outcomes:
measure: Percentage of Participants With Transfusion Avoidance After Day 1 Through Week 36
timeFrame: Day 1 through week 36
measure: Percentage of Participants With Transfusion Avoidance From Week 4 Through Week 36
timeFrame: Week 4 through week 36
measure: Percentage of Participants With Breakthrough Hemolysis After Day 1 Through Week 36
timeFrame: Day 1 through week 36
measure: Percentage of Participants With Breakthrough Hemolysis From Week 4 Through Week 36
timeFrame: Week 4 (day 29) through week 36
measure: Percentage of Participants With Hemoglobin Stabilization After Day 1 Through Week 36
timeFrame: Day 1 through week 36
measure: Percentage of Participants With Hemoglobin Stabilization From Week 4 Through Week 36
timeFrame: Week 4 (day 29) through week 36
measure: Percentage of Participants With Adequate Control of LDH From Week 8 Through Week 36
timeFrame: Week 8 (day 57) through week 36
measure: Percentage of Participants With Adequate Control of LDH After Day 1 Though Week 36
timeFrame: Day 1 through week 36
measure: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Week 8 Through Week 36
timeFrame: Week 8 through week 36
measure: Percentage of Participants Who Maintained Adequate Control of Hemolysis After Day 1 Through Week 36
timeFrame: Day 1 through week 36
measure: Percentage of Participants With Normalization of LDH From Week 8 Through Week 36
timeFrame: Week 8 (day 57) through week 36
measure: Percentage of Participants With Normalization of LDH After Day 1 Through Week 36
timeFrame: Day 1 through week 36
measure: Change in Fatigue as Measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline to Week 36
timeFrame: From baseline to week 36
measure: Change in Physical Function (PF) Score on the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 Items (EORTC-QLQ-C30) From Baseline to Week 36
timeFrame: From baseline to week 36
measure: Change in Global Health Status (GHS)/QoL Scale Score on the EORTC-QLQ-C30 From Baseline to Week 36
timeFrame: From baseline to week 36
measure: Rate of RBCs Transfused Per Protocol Algorithm After Day 1 Through Week 36
timeFrame: Day 1 through week 36
measure: Rate of RBCs Transfused Per Protocol Algorithm From Week 4 Through Week 36
timeFrame: Week 4 through week 36
measure: Number of Units of RBCs Transfused Per Protocol Algorithm After Day 1 Through Week 36
timeFrame: Day 1 through week 36
measure: Number of Units of RBCs Transfused Per Protocol Algorithm From Week 4 Through Week 36
timeFrame: Week 4 through week 36
measure: Change in Hemoglobin Levels From Baseline to Week 36
timeFrame: From baseline to week 36
measure: Incidence of Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: Up to week 29
measure: Incidence of Treatment-emergent Adverse Events (TEAEs) of Special Interest
timeFrame: Up to week 29
measure: Incidence of TEAEs Leading to Treatment Discontinuation
timeFrame: Up to week 29
measure: Change in Total CH50 From Baseline to Week 36
timeFrame: From baseline to week 36
measure: Percent Change in Total CH50 From Baseline to Week 36
timeFrame: From baseline to week 36
measure: Concentration of Total C5 in Plasma Through Week 62
timeFrame: Through week 62
measure: Concentrations of Total Pozelimab in Serum Through Week 62
timeFrame: Through week 62
measure: Concentrations of Total Cemdisiran in Plasma Through Week 32
timeFrame: Through week 32
measure: Concentrations of Total Eculizumab in Serum Through Week 40
timeFrame: Through week 40
measure: Concentrations of Total Ravulizumab in Plasma Through Week 44
timeFrame: Through week 44
measure: Incidence of Treatment Emergent Anti-drug Antibodies (ADAs) to Pozelimab Through Week 62
timeFrame: Through week 62
measure: Incidence of Treatment Emergent ADAs to Cemdisiran Through Week 62
timeFrame: Through week 62
Other outcomes:
Locations:
city: Whittier
country: United States
facility: Regeneron Research Facility
state: California
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: