NCT04888507已完成2 期
A Single Arm, Open-Label Study to Assess the Safety, Efficacy, and Pharmacodynamic Effects of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Switch From Eculizumab Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- OLTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The primary objective of the study is to evaluate the safety and tolerability of pozelimab and cemdisiran combination therapy in participants with PNH who switch from eculizumab therapy
The secondary objectives of the study are:
- To evaluate the effect of the combination treatment on the following parameters of intravascular hemolysis: lactate dehydrogenase (LDH) control, breakthrough hemolysis, and inhibition of CH50
- To evaluate the effect of the combination treatment on the stability of LDH during the transition period from eculizumab monotherapy to combination with pozelimab and cemdisiran
- To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements
- To evaluate the effect of the combination treatment on hemoglobin levels
- To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life (HRQoL)
- To assess the concentrations of total pozelimab and eculizumab in serum; and total cemdisiran and C5 protein in plasma
- To assess the immunogenicity of pozelimab and cemdisiran
- To assess safety after dose intensification
- To evaluate the long-term safety and efficacy of the combination treatment in an optional open-label extension period (OLEP)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 paroxysmal nocturnal hemoglobinuria confirmed by a history of high-sensitivity flow cytometry from prior testing
- •Treated with stable (ie, no change in dose or frequency) eculizumab therapy at the labeled dosing regimen or a higher dose and/or more frequently administered than labeled for at least 12 weeks prior to screening visit
排除标准
- •History of bone marrow transplantation or receipt of an organ transplant
- •Body weight <40 kg at screening
- •Current plans for modification of the following background concomitant medications, as applicable, during screening and treatment period: erythropoietin, immunosuppressive drugs, corticosteroids, anti-thrombotic agents, anticoagulants, iron supplements, and folic acid as described in the protocol
- •Any use of complement inhibitor therapy other than eculizumab in the 12 weeks prior to the screening visit or planned use during the study
- •Known hypocellular bone marrow based on a history of reduced age-adjusted bone marrow cellularity and/or bone marrow cellularity ≤25%
- •No documented meningococcal vaccination within 5 years prior to screening visit unless it is documented that vaccination has been administered during the screening period and prior to initiation of study treatment
- •Unable to take antibiotics for meningococcal prophylaxis, if required by local standard of care
- •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
- •Documented positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as described in the protocol
- •Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
- •Recent, unstable medical conditions, excluding PNH and PNH-related complications, within the past 3 months prior to screening visit as described in the protocol
- •Anticipated need for major surgery during the study
- •NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply.
研究组 & 干预措施
Pozelimab+Cemdisiran
Experimental
干预措施: Pozelimab (Drug)
Pozelimab+Cemdisiran
Experimental
干预措施: Cemdisiran (Drug)
结局指标
主要结局
OLTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to Day 225
次要结局
- OLTP: Number of Participants With Cemdisiran ADA(Baseline through Week 32)
- OLTP: Number of Participants Who Received Dose Intensification With TEAEs(Baseline through Week 32)
- OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP(Baseline, Days 57, 113, 169, 225, 281, 365 of the OLEP)
- OLTP: Percent Change in Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period(Screening (Day 1) through Day 225)
- OLTP: Percent Change in LDH From Pre-treatment Through Day 29(Screening (Day 1) through Day 29)
- OLTP: Percentage of Participants Who Were Transfusion-free From Baseline Through Week 32(Baseline through Week 32)
- OLTP: Percentage of Participants Who Were Transfusion-free From Week 4 Through Week 32(Week 4 through Week 32)
- OLTP: Rate of Red Blood Cell (RBC) Transfusions From Baseline Through Week 32(Baseline through Week 32)
- OLTP: Rate of RBC Transfusions From Week 4 Through Week 32(Week 4 through Week 32)
- OLTP: Number of RBC Units Transfused From Baseline Through Week 32(Baseline through Week 32)
- OLTP: Number of RBC Units Transfused From Week 4 Through Week 32(Week 4 through Week 32)
- OLEP: Number of Participants With TEAEs(Day 1 through Week 52 of the OLEP)
- OLTP: Percentage of Participants With Breakthrough Hemolysis From Baseline Through Week 32(Baseline through Week 32)
- OLTP: Percentage of Participants With Breakthrough Hemolysis From Week 4 Through Week 32(Week 4 through Week 32)
- OLTP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 32(Day 1 through Week 32)
- OLTP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Week 8 Through Week 32(Week 8 through Week 32)
- OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit(Days 1, 8, 15, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225)
- OLTP: Number of Participants With Normalization of Their LDH at Each Visit(Days 1, 8, 15, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225)
- OLTP: Average LDH From Baseline Through Week 32(Baseline through Week 32)
- OLTP: Average LDH From Week 8 Through Week 32(Week 8 through Week 32)
- OLTP: Percentage of Participants With Hemoglobin Stabilization From Baseline Through Week 32(Baseline through Week 32)
- OLTP: Percentage of Participants With Hemoglobin Stabilization From Week 4 Through Week 32(Week 4 through Week 32)
- OLTP: Change From Baseline in Hemoglobin Levels(Baseline, Week 32)
- OLEP: Average LDH From Day 1 Through Week 24 of the OLEP(Day 1 through Week 24 of the OLEP)
- OLTP: Change From Baseline in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score(Baseline, Week 32)
- OLTP: Change From Baseline in Health Related Quality of Life (HRQoL) as Measured by the Global Health Status Subscale of the European Organization for Research and Treatment of Cancer (EORTC)- Quality of Life Cancer Patients Questionnaire (QLQ) - 30 Scale(Baseline, Week 32)
- OLTP: Change From Baseline in Physical Function (PF) Scores on the EORTC QLQ-C30(Baseline, Week 32)
- OLTP: Change From Baseline in Total Complement Hemolytic Activity Assay (CH50)(Baseline through Week 32)
- OLTP and OLEP: Concentration of Total Pozelimab in Serum(Pre-dose Days 28, 56, 84, 112, 140, 168, 196, 224, 392, 588; Post-dose Day 28)
- OLTP: Concentration of Total Eculizumab in Serum(Pre-dose Days 0, 14, 28, 56, 84, 112, 140, 168, 196, 224)
- OLTP and OLEP: Concentration of Total Cemdisiran in Plasma(Pre-dose and Post-dose Days 0, 84, 196, 224, 588)
- OLTP and OLEP: Concentration of Total C5 in Plasma(Pre-dose Days 0, 7, 14, 28, 56, 84, 112, 140, 168, 196, 224, 392, 588)
- OLTP: Number of Participants With Pozelimab Anti-drug Antibodies (ADA)(Baseline through Week 32)
- OLEP: Percent Change in LDH From Day 1 Through Week 24 of the OLEP(Day 1 through Week 24 of the OLEP)
- OLEP: Percent Change in LDH From Day 1 Through Week 52 of the OLEP(Day 1 through Week 52 of the OLEP)
- OLEP: Percentage of Participants Who Were Transfusion-free From Day 1 Through Week 24 of the OLEP(Day 1 through Week 24 of the OLEP)
- OLEP: Percentage of Participants Who Were Transfusion-free From Day 1 Through Week 52 of the OLEP(Day 1 through Week 52 of the OLEP)
- OLEP: Rate of RBC Transfusions From Day 1 Through Week 24 of the OLEP(Day 1 through Week 24 of the OLEP)
- OLEP: Rate of RBC Transfusions From Day 1 Through Week 52 of the OLEP(Day 1 through Week 52 of the OLEP)
- OLEP: Number of RBC Units Transfused From Day 1 Through Week 24 of the OLEP(Day 1 through Week 24 of the OLEP)
- OLEP: Number of RBC Units Transfused From Day 1 Through Week 52 of the OLEP(Day 1 through Week 52 of the OLEP)
- OLEP: Percentage of Participants With Breakthrough Hemolysis From Day 1 Through Week 24 of the OLEP(Day 1 through Week 24 of the OLEP)
- OLEP: Percentage of Participants With Breakthrough Hemolysis From Day 1 Through Week 52 of the OLEP(Day 1 through Week 52 of the OLEP)
- OLEP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 24 of the OLEP(Day 1 through Week 24 of the OLEP)
- OLEP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 52 of the OLEP(Day 1 through Week 52 of the OLEP)
- OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP(Baseline, Days 57, 113, 169, 225, 281, 365 of the OLEP)
- OLEP: Average LDH From Day 1 Through Week 52 of the OLEP(Day 1 through Week 52 of the OLEP)
- OLEP: Percentage of Participants With Hemoglobin Stabilization From Day 1 Through Week 24 of the OLEP(Day 1 through Week 24 of the OLEP)
- OLEP: Percentage of Participants With Hemoglobin Stabilization From Day 1 Through Week 52 of the OLEP(Day 1 through Week 52 of the OLEP)
- OLEP: Change From Baseline in Hemoglobin Levels(Day 1 and Week 52 of the OLEP)
- OLEP: Change From Baseline in FACIT-Fatigue Score(Day 1 and Week 52 of the OLEP)
- OLEP: Change From Baseline in HRQoL as Measured by the Global Health Status Subscale of the EORTC-QLQ-30 Scale(Day 1 and Week 52 of the OLEP)
- OLEP: Change From Baseline in PF Scores on the EORTC QLQ-C30(Day 1 and Week 52 of the OLEP)
- OLEP: Change From Baseline in CH50(Baseline, Week 16, Week 32, Week 52 of the OLEP)
- OLEP: Number of Participants With Pozelimab ADA(Day 1 through Week 52 of the OLEP)
- OLEP: Number of Participants With Cemdisiran ADA(Day 1 through Week 52 of the OLEP)
研究者
研究点 (1)
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