NCT05131204终止3 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Percent Change in Lactate Dehydrogenase (LDH) From Baseline to Week 36
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
- •Treated with eculizumab or ravulizumab prior to screening visit as described in the protocol Note: Biosimilars are not permitted, unless approved by the Sponsor
排除标准
- •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
- •Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
- •Body weight < 40 kilograms at screening visit
- •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
- •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.
- •Any contraindication for receiving Neisseria meningitidis vaccination.
- •Positive for hepatitis B, and/ or hepatitis C as described in the protocol
- •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
- •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.
- •Patients with functional or anatomic asplenia
- •Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
研究组 & 干预措施
Pozelimab and Cemdisiran
Experimental
Randomized 1:1
干预措施: Eculizumab (Drug)
Pozelimab and Cemdisiran
Experimental
Randomized 1:1
干预措施: Pozelimab (Drug)
Pozelimab and Cemdisiran
Experimental
Randomized 1:1
干预措施: Ravulizumab (Drug)
Anti-C5 standard-of-care
Experimental
Randomized 1:1
干预措施: Eculizumab (Drug)
Anti-C5 standard-of-care
Experimental
Randomized 1:1
干预措施: Ravulizumab (Drug)
Pozelimab and Cemdisiran
Experimental
Randomized 1:1
干预措施: Cemdisiran (Drug)
结局指标
主要结局
Percent Change in Lactate Dehydrogenase (LDH) From Baseline to Week 36
时间窗: From baseline to week 36
次要结局
- Percentage of Participants With Transfusion Avoidance After Day 1 Through Week 36(Day 1 through week 36)
- Percentage of Participants With Transfusion Avoidance From Week 4 Through Week 36(Week 4 through week 36)
- Percentage of Participants With Breakthrough Hemolysis After Day 1 Through Week 36(Day 1 through week 36)
- Percentage of Participants With Breakthrough Hemolysis From Week 4 Through Week 36(Week 4 (day 29) through week 36)
- Percentage of Participants With Hemoglobin Stabilization After Day 1 Through Week 36(Day 1 through week 36)
- Percentage of Participants With Hemoglobin Stabilization From Week 4 Through Week 36(Week 4 (day 29) through week 36)
- Percentage of Participants With Adequate Control of LDH From Week 8 Through Week 36(Week 8 (day 57) through week 36)
- Percentage of Participants With Adequate Control of LDH After Day 1 Though Week 36(Day 1 through week 36)
- Percentage of Participants Who Maintained Adequate Control of Hemolysis From Week 8 Through Week 36(Week 8 through week 36)
- Percentage of Participants Who Maintained Adequate Control of Hemolysis After Day 1 Through Week 36(Day 1 through week 36)
- Percentage of Participants With Normalization of LDH From Week 8 Through Week 36(Week 8 (day 57) through week 36)
- Percentage of Participants With Normalization of LDH After Day 1 Through Week 36(Day 1 through week 36)
- Change in Fatigue as Measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline to Week 36(From baseline to week 36)
- 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(From baseline to week 36)
- Incidence of TEAEs Leading to Treatment Discontinuation(Up to week 29)
- Change in Global Health Status (GHS)/QoL Scale Score on the EORTC-QLQ-C30 From Baseline to Week 36(From baseline to week 36)
- Rate of RBCs Transfused Per Protocol Algorithm After Day 1 Through Week 36(Day 1 through week 36)
- Rate of RBCs Transfused Per Protocol Algorithm From Week 4 Through Week 36(Week 4 through week 36)
- Number of Units of RBCs Transfused Per Protocol Algorithm After Day 1 Through Week 36(Day 1 through week 36)
- Number of Units of RBCs Transfused Per Protocol Algorithm From Week 4 Through Week 36(Week 4 through week 36)
- Change in Hemoglobin Levels From Baseline to Week 36(From baseline to week 36)
- Incidence of Treatment Emergent Serious Adverse Events (SAEs)(Up to week 29)
- Incidence of Treatment-emergent Adverse Events (TEAEs) of Special Interest(Up to week 29)
- Change in Total CH50 From Baseline to Week 36(From baseline to week 36)
- Percent Change in Total CH50 From Baseline to Week 36(From baseline to week 36)
- Concentration of Total C5 in Plasma Through Week 62(Through week 62)
- Concentrations of Total Pozelimab in Serum Through Week 62(Through week 62)
- Concentrations of Total Cemdisiran in Plasma Through Week 32(Through week 32)
- Concentrations of Total Eculizumab in Serum Through Week 40(Through week 40)
- Concentrations of Total Ravulizumab in Plasma Through Week 44(Through week 44)
- Incidence of Treatment Emergent Anti-drug Antibodies (ADAs) to Pozelimab Through Week 62(Through week 62)
- Incidence of Treatment Emergent ADAs to Cemdisiran Through Week 62(Through week 62)
研究者
研究点 (1)
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