Ravulizumab-Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria who are Complement Inhibitor Treatment-Naive or Have Not Recently Received Complement Inhibitor Therapy

• Register: EUCTR
• Last refreshed on: 16 May 2022
• Main ID: EUCTR2020-004486-40-ES
• Date of registration: 11/03/2022
• Prospective Registration: Yes
• Primary sponsor: Regeneron Pharmaceuticals, Inc.
• Public title: Ravulizumab-Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria who are Complement Inhibitor Treatment-Naive or Have Not Recently Received Complement Inhibitor Therapy
• Scientific title: A RANDOMIZED, OPEN-LABEL, RAVULIZUMAB-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF POZELIMAB AND CEMDISIRAN COMBINATION THERAPY IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WHO ARE COMPLEMENT INHIBITOR TREATMENT-NAIVE OR HAVE NOT RECENTLY RECEIVED COMPLEMENT INHIBITOR THERAPY
• Date of first enrolment: 09/05/2022
• Target sample size: 124
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004486-40
• 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, Canada, China, Colombia, France, Greece, Italy, Japan, Jordan, Korea, Republic of, Malaysia, Mexico, Netherlands, Peru, Poland, Portugal, Romania, Singapore, South Africa, 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 high-sensitivity flow cytometry testing with PNH granulocytes described in the protocol
2. Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms described in the protocol 3. LDH level =2 × ULN at the screening visit

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 108
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion criteria:
1. Prior treatment with a complement inhibitor within 6 months prior to screening visit, unless patient was treated with eculizumab or ravulizumab and has documented C5 variant R885H/C in which case there is no exclusion of such patients
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 for 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. Unable to take antibiotics for meningococcal prophylaxis (if required by local ravulizumab prescribing information, where available, or national guidelines/local practice or if necessary when vaccination is less than 2 weeks from study treatment initiation)
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 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-

Primary Outcome(s)

Main Objective: To evaluate the effect on hemolysis and red blood cell (RBC) transfusions over a 24-week treatment period of pozelimab and cemdisiran combination treatment versus ravulizumab treatment in patients with active Paroxysmal Nocturnal Hemoglobinuria (PNH) who are complement inhibitor treatment-naive or have not recently received complement inhibitor therapy

Secondary Objective: • Evaluate the effect of pozelimab and cemdisiran combination treatment versus ravulizumab treatment on the following:
- Measures of hemolysis
- Transfusion parameters
- Hemoglobin levels
- Fatigue as assessed by Clinical Outcome Assessments (COAs)
- HRQoL as assessed by COAs
- Safety and tolerability
- Complement activation
• To assess the concentrations of total pozelimab and total ravulizumab in serum and total cemdisiran and total complement factor 5 (C5) protein in plasma
• To assess the immunogenicity of pozelimab and cemdisiran

Primary end point(s): 1. Proportion of patients with adequate control of hemolysis
2. Proportion of patients with transfusion avoidance

Timepoint(s) of evaluation of this end point: 1. Between week 4 and week 24, inclusive
2. Day 1 through week 24

Secondary Outcome(s)

Secondary end point(s): 1. Proportion of patients with breakthrough hemolysis
2. Proportion of patients with hemoglobin stabilization
3. Proportion of patients with normalization of LDH
4. Percent change in LDH
5. Change in fatigue as measured by the FACIT-Fatigue Scale
6. Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)
7. Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30
8. Rate of RBC transfusion per protocol algorithm
9. Number of units of RBC transfusion per protocol algorithm
10. Time to first LDH =1.5 × ULN
11. Time to first LDH =1.0 × ULN
12. Percentage of days with LDH =1.5 × ULN
13. Change in hemoglobin levels
14. Incidence and severity of treatment emergent serious adverse events (SAEs)
15. Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest
16. Incidence and severity of TEAE leading to treatment discontinuation
17. Change in total CH50
18. Percent change in total CH50
19. Concentration of total C5 in plasma
20. Concentrations of total pozelimab in serum
21. Concentrations of total cemdisiran in plasma
22. Concentrations of total ravulizumab in serum
23. Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab
24. Incidence of treatment emergent ADAs to cemdisiran

Timepoint(s) of evaluation of this end point: 1. Post-baseline day 1 through week 24
2. Day 1 (post-baseline) through week 24
3. Between week 4 through week 24, inclusive
4-5. From baseline to week 24
6. Baseline to week 24
7. From baseline to week 24
8-9. Day 1 through week 24
10-11. Up to Week 24
12. Between week 4 and week 24, inclusive
13. From baseline to week 24
14-16. Up to 24 weeks
17-18. From baseline to week 24
19-20. Up to 50 weeks
21. Up to 20 weeks
22. Up to 34 weeks
23-24. Up to 50 weeks

Secondary ID(s)

R3918-PNH-2021

Source(s) of Monetary Support

Regeneron Pharmaceuticals, Inc.

Ethics review

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