Efficacy and Safety of the Combination of Pozelimab and Cemdisiran Versus Continued Eculizumab or Ravulizumab Treatment in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria

JRCT ID: jRCT2031240002

Registered date:02/04/2024

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Paroxysmal Nocturnal Hemoglobinuria
• Date of first enrollment: 06/01/2023
• Target sample size: 0
• Countries of recruitment: Brazil,Japan,China,Japan,France,Japan,Germany,Japan,Greece,Japan,Hungary,Japan,India,Japan,Italy,Japan,Malaysia,Japan,Mexico,Japan,Philippines,Japan,Poland,Japan,Romania,Japan,Singapore,Japan,South Korea,Japan,Spain,Japan,Taiwan,Japan,Thailand,Japan,Turkey,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Pozelimab and cemdisiran arm:
-Drug: Cemdisiran, Administered per protocol
-Drug: Eculizumab, Administered per protocol
-Drug: Pozelimab, Administered per protocol
-Drug: Ravulizumab, Administered per protocol

Anti-C5 standard-of-care arm:
-Drug: Eculizumab, Administered per protocol
-Drug: Ravulizumab, Administered per protocol

Randomized 1:1

Outcome(s)

• Primary Outcome: Percent change in lactate dehydrogenase (LDH) [Time Frame: From baseline to week 36]

Secondary Outcome

1. Proportion of transfusion avoidance [Time Frame: Day 1 through week 36, inclusive]
2. Proportion of patients with break-through hemolysis, in patients with a baseline LDH =<1.5 x ULN [Time Frame: Day 1 through week 36, in-clusive]
3. Proportion of patients with hemo-globin stabilization [Time Frame: Day 1 through week 36, inclusive]
4. Proportion of patients with maintenance of adequate control of hemolysis [Time Frame: week 8 through week 36, inclusive]
5. Proportion of patients with ade-quate control of hemolysis [Time Frame: week 8 through week 36, in-clusive]
6. Proportion of patients with nor-malization of LDH [Time Frame: week 8 through week 36, inclusive]
7. Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale [Time Frame: From baseline to week 36]
8. 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) [Time Frame: From baseline to week 36]
9. Change in global health status (GHS)/QoL scale score on the EORTC-QLQ-C30 [Time Frame: From baseline to week 36]
10. Proportion of transfusion avoidance [Time Frame: week 4 through week 36, inclusive]
11. Proportion of patients with break-through hemolysis, in patients with a baseline LDH =<1.5 x ULN [Time Frame: week 4 through week 36, in-clusive ]
12. Proportion of patients with hemo-globin stabilization [Time Frame: week 4 through week 36, inclusive]
13. Proportion of patients with maintenance of adequate control of hemolysis[Time Frame: day 1 through week 36, inclusive]
14. Proportion of patients with ade-quate control of hemolysis [Time Frame: day 1 through week 36, inclu-sive]
15. Proportion of patients with nor-malization of LDH [Time Frame: day 1 through week 36, inclusive]
16. Rate and number of units of RBCs transfused per protocol algorithm [Time Frame: day 1 through week 36, and from week 4 through week 36]
17. Change in hemoglobin levels [Time Frame: baseline to week 36]
18. Incidence and severity of treat-ment-emergent SAEs, TEAEs of spe-cial interest and TEAEs leading to treatment discontinuation over 36 weeks
19. Change and percent change in total CH50 [Time Frame: baseline to week 36]
20. Concentration of total C5 in plasma [Time Frame: throughout the study]
21. Concentrations of total pozelimab in serum [Time Frame: throughout the study]
22. Concentrations of cemdisiran in plasma [Time Frame: throughout the study]
23. Concentrations of total eculizumab or ravulizumab in serum [Time Frame: throughout the study]
24. Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab [Time Frame: throughout the study]
25. Incidence of treatment emergent ADAs to cemdisiran assessed over 36 weeks

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
2. Ongoing treatment with eculizumab 900 mg IV Q 14 days for at least 12 weeks prior to screening visit. or Ongoing treatment with ravulizumab IV Q8W based on BW for at least 24 weeks prior to screening visit. Note: Biosimilars are not permitted, unless approved by the Sponsor.
Other protocol-defined Inclusion Criteria apply

Exclude criteria

1. Patients with a screening LDH >1.5 x ULN who have not taken their C5 inhibitor within the labeled dose in-terval at the dose prior to the screen-ing LDH assessment.
2. Receipt of an organ transplant, history of bone marrow transplanta-tion 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 visi or planned use during the study with the exception of study treatments.
5. Not meeting meningococcal vac-cination requirements for eculizumab or ravulizumab according to the current local pre-scribing 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 hepatitis B surface antigen or hepatitis C virus RNA during screening 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 interven-tional 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 ravuli-zumab.
10. Patients with functional or ana-tomic asplenia
Other protocol-defined Exclusion Criteria apply

Related Information

• Primary Sponsor: Aurand Lisa
• Secondary ID(s): NCT05131204,2020-002761-33