Efficacy and Safety of the Combination of Pozelimab and Cemdisiran versus continued Eculizumab or Ravulizumab Treatment in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria

• Register: EUCTR
• Last refreshed on: 26 September 2023
• Main ID: EUCTR2020-002761-33-ES
• Date of registration: 11/03/2022
• Prospective Registration: Yes
• Primary sponsor: Regeneron Pharmaceuticals, Inc.
• Public title: Efficacy and Safety of the Combination of Pozelimab and Cemdisiran versus continued Eculizumab or Ravulizumab Treatment in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria
• Scientific 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
• Date of first enrolment: 09/05/2022
• Target sample size: 140
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-002761-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Brazil, Colombia, France, Germany, Greece, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Philippines, Poland, Portugal, Romania, Singapore, Spain, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trial Information
• Affiliation: Regeneron Pharmaceuticals, Inc.

• Name: Clinical Trial Information
• Affiliation: Regeneron Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

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

Note: Other protocol-defined Inclusion Criteria apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 112
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28

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 Exclusion Criteria apply


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Paroxysmal nocturnal hemoglobinuria (PNH)
MedDRA version: 21.1 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Product Name: Pozelimab
Product Code: REGN3918
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pozelimab
Current Sponsor code: REGN3918
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-

Product Name: Cemdisiran
Product Code: ALN-CC5
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CEMDISIRAN
Current Sponsor code: ALN-CC5
Other descriptive name: CEMDISIRAN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-

Trade Name: ULTOMIRIS ™ (ravulizumab-cwvz)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Ravulizumab
Other descriptive name: Ravulizumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Product Name: Pozelimab
Product Code: REGN3918
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Pozelimab
Current Sponsor code: REGN3918
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-

Trade Name: Soliris ™ (eculizumab)
Product Name: Eculizumab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Eculizumab
CAS Number: 219685-50-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Secondary Objective: • 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)
- 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

Primary end point(s): Percent change in lactate dehydrogenase (LDH)

Main Objective: • To evaluate the effect of pozelimab and cemdisiran combination therapy on hemolysis, as assessed by 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.

Timepoint(s) of evaluation of this end point: From baseline to week 36

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Day 1 through week 36
2. Week 4 through week 36
3. Day 1 through week 36
4. Week 4 (day 29) through week 36
5. Day 1 through week 36
6. Week 4 (day 29) through week 36
7. Day 1 through week 36
8. Week 8 (day 57) through week 36
9. Day 1 through week 36
10. Week 8 (day 57) through week 36
11-13. From baseline to week 36
14. Day 1 through week 36
15. Week 4 through week 36
16. Day 1 through week 36
17. Week 4 through week 36
18. From baseline to week 36
19-21. Up to 88 weeks
22-23. From baseline to week 36
24-25. Through week 62
26. Through week 32
27. Through week 40
28. Through week 44
29-30. Through week 62

Secondary end point(s): 1. Proportion of patients with transfusion avoidance
2. Proportion of patients with transfusion avoidance
3. Proportion of patients with breakthrough hemolysis
4. Proportion of patients with breakthrough hemolysis
5. Proportion of patients with hemoglobin stabilization
6. Proportion of patients with hemoglobin stabilization
7. Proportion of patients with adequate control of LDH
8. Proportion of patients with adequate control of LDH
9. Proportion of patients with normalization of LDH
10. Proportion of patients with normalization of LDH
11. Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale
12. 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)
13. Change in global health status (GHS)/QoL scale score on the EORTC-QLQ-C30
14. Rate of RBCs transfused per protocol algorithm
15. Rate of RBCs transfused per protocol algorithm
16. Number of units of RBCs transfused per protocol algorithm
17. Number of units of RBCs transfused per protocol algorithm
18. Change in hemoglobin levels
19. Incidence and severity of treatment emergent serious adverse events (SAEs)
20. Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest
21. Incidence and severity TEAEs leading to treatment discontinuation
22. Change in total CH50
23. Percent change in total CH50
24. Concentration of total C5 in plasma
25. Concentrations of total pozelimab in serum
26. Concentrations of total cemdisiran in plasma
27. Concentrations of total eculizumab
28. Concentrations of total ravulizumab in serum
29. Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab
30. Incidence of treatment emergent ADAs to cemdisiran

Secondary ID(s)

2020-002761-33-IT

R3918-PNH-2022

Source(s) of Monetary Support

Regeneron Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 06/05/2022
Contact: