NCT05133531进行中（未招募）3 期
A Randomized, Open-Label, C5 Inhibitor-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
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 202
- 试验地点
- 134
- 主要终点
- Percent change in lactate dehydrogenase (LDH)
研究概览
简要总结
This study is researching a clinical treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on people with paroxysmal nocturnal hemoglobinuria (PNH). The aim of the study is to see how safe and effective the pozelimab + cemdisiran combination is for people with PNH and how the combination compares with 2 existing treatments: ravulizumab and eculizumab.
The pozelimab + cemdisiran combination may be referred to as "study drugs". Ravulizumab and eculizumab may also be called the "comparator drug".
The study is looking at several research questions, including:
- How effective is the pozelimab + cemdisiran combination compared to ravulizumab?
- How effective is pozelimab + cemdisiran combination compared to eculizumab?
- What side effects may happen from taking the study drugs?
- How much study drugs are in the blood at different times?
- Whether the body makes antibodies against the study drugs (which could make the study drugs less effective or could lead to side effects)
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 high-sensitivity flow cytometry testing with PNH granulocytes or monocytes as described in the protocol
- •Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms as described in the protocol
- •LDH level ≥2 × ULN at the screening visit
- •Willing and able to comply with clinic/remote visits and study-related procedures, including completion of the full series of meningococcal vaccinations required per protocol
排除标准
- •Prior treatment with eculizumab within 3 months prior to screening, ravulizumab within 6 months prior to screening, or other complement inhibitors within 5 half-lives of the respective agent prior to screening
- •Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
- •Body weight <40 kilograms at screening visit
- •Planned use of any complement inhibitor therapy other than study drugs during the treatment period
- •Not meeting meningococcal vaccination requirements and, at a minimum documentation of quadrivalent meningococcal vaccination within 5 years prior to the screening visit and serotype B vaccine within 3 years prior to the screening visit as described in the protocol.
- •Any contraindication for receiving Neisseria meningitidis vaccinations (serotypes ACWY and B).
- •Unable to take antibiotics for meningococcal prophylaxis (if required by local ravulizumab [Cohort A] or eculizumab [Cohort B] prescribing information, where available, or national guidelines/local practice, or if necessary when administration of the first dose of the quadrivalent meningococcal vaccine [serotype ACWY] or the second dose of the serotype B meningococcal vaccine [when available] is less than 2 weeks prior to study treatment initiation) as described in the protocol
- •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 history of active, uncontrolled, ongoing systemic autoimmune diseases
- •Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
研究组 & 干预措施
Cohort A
Experimental
Randomized 1:1
干预措施: Ravulizumab (Drug)
Cohort A
Experimental
Randomized 1:1
干预措施: Pozelimab (Drug)
Cohort A
Experimental
Randomized 1:1
干预措施: Cemdisiran (Drug)
Cohort B
Experimental
Randomized 1:1
干预措施: Pozelimab (Drug)
Cohort B
Experimental
Randomized 1:1
干预措施: Cemdisiran (Drug)
Cohort B
Experimental
Randomized 1:1
干预措施: Eculizumab (Drug)
结局指标
主要结局
Percent change in lactate dehydrogenase (LDH)
时间窗: From baseline to week 26
Cohort A
Transfusion avoidance
时间窗: From post-baseline day 1 through week 26
Cohort B Not requiring a red blood cell (RBC) transfusion per the protocol
Adequate control of hemolysis
时间窗: From week 8 through week 26, inclusive
Cohort B LDH ≤1.5 × ULN at each visit
次要结局
- Maintenance of adequate control of hemolysis(From week 8 through week 26, inclusive)
- Breakthrough hemolysis(From post-baseline day 1 through week 26)
- Adequate control of hemolysis(From week 8 through week 26, inclusive)
- Hemoglobin stabilization(From day 1 (post-baseline) through week 26)
- Normalization of LDH(Between week 8 through week 26, inclusive)
- Transfusion avoidance(Day 1 through week 26)
- Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale(From baseline to week 26)
- Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)(From baseline to week 26)
- Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30(From baseline to week 26)
- Percent change in LDH(From baseline to week 26)
- Rate of RBC transfused(Post-baseline Day 1 through week 26)
- Number of units of RBC transfused(Post-baseline Day 1 through week 26)
- Time to first LDH ≤1.5 × ULN(Up to Week 26)
- Time to first LDH ≤1.0 × ULN(Up to Week 26)
- Percentage of days with LDH ≤1.5 × ULN(Between week 8 and week 26, inclusive)
- Change in hemoglobin levels(From baseline to week 26)
- Incidence and severity of treatment emergent serious adverse events (SAEs)(Up to 26 weeks)
- Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest(Up to 26 weeks)
- Incidence and severity of TEAEs leading to treatment discontinuation(Up to 26 weeks)
- Change in total CH50(From baseline to week 26)
- Percent change in total CH50(From baseline to week 26)
- Concentration of total C5 in plasma(Up to 60 weeks)
- Concentrations of total pozelimab in serum(Up to 60 weeks)
- Concentrations of cemdisiran in plasma(Up to 60 weeks)
- Concentrations of total ravulizumab in serum(Up to 34 weeks)
- Concentrations of total eculizumab in serum(Up to 30 weeks)
- Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab(Up to 60 weeks)
- Incidence of treatment emergent ADAs to cemdisiran(Up to 60 weeks)
研究者
研究点 (134)
Loading locations...
相似试验
终止
3 期
Efficacy and Safety of the Combination of Pozelimab and Cemdisiran Versus Continued Eculizumab or Ravulizumab Treatment in Adult Patients With Paroxysmal Nocturnal HemoglobinuriaParoxysmal Nocturnal HemoglobinuriaNCT05131204Regeneron Pharmaceuticals2
已完成
3 期
A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Combination With Methotrexate in the Treatment of Disease Modifying Antirheumatic Drugs (DMARD)-naïve Adults With Early Active Rheumatoid ArthritisRheumatoid ArthritisNCT01519791UCB Pharma SA880
已完成
3 期
A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Combination With Methotrexate in the Treatment of Disease Modifying Antirheumatic Drugs (DMARD)-naïve Adults With Early Active Rheumatoid ArthritisRheumatoid ArthritisNCT01521923UCB Pharma359
终止
1 期
A Phase Ib/II, Multicenter, Single Arm, Open-Label Study, To Evaluate the Safety, Tolerability and Efficacy of the BL-8040 and Atezolizumab Combination for Maintenance Treatment in Subjects With Acute Myeloid Leukemia Who Are 60 Years or Older - The BATTLE StudyAcute Myeloid LeukemiaNCT03154827BioLineRx, Ltd.1
已完成
1 期
A First in Human Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics Effects of OC514Cancer CachexiaNCT05264038Oncocross Australia Pty Ltd.23