A Phase 3, Randomized, Parallel-Group, Multicenter, Open-Label, Pharmacokinetic, Noninferiority Study of Ravulizumab Administered Subcutaneously Versus Intravenously in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With Eculizumab
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 139
- 试验地点
- 1
- 主要终点
- Ctrough Serum Concentration of Ravulizumab
研究概览
简要总结
The primary objective of this study is to evaluate pharmacokinetics (PK) of ravulizumab administered subcutaneously via an on-body delivery system (OBDS) compared with intravenously administered ravulizumab in adult participants with PNH who are clinically stable on eculizumab for at least 3 months prior to study entry.
详细描述
The study will consist of up to a 30-day Screening Period, a 10-week Randomized Treatment Period, and an Extension Period of up to 172 weeks.
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
- •Male or female ≥18 years of age
- •Treated with eculizumab for PNH for at least 3 months prior to Day 1
- •LDH level ≤1.5 × upper limit of normal (ULN) at screening
- •PNH diagnosis confirmed by documented high-sensitivity flow cytometry.
- •Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
- •Body weight ≥40 to <100 kilogram (kg)
- •Female participants of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
- •Willing and able to give written informed consent and comply with study visit schedule.
排除标准
- •More than 1 LDH value > 2 × ULN within the 3 months prior to study entry
- •History of bone marrow transplantation.
- •History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the Investigator or Sponsor, would preclude participation.
- •Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH).
- •Females who are pregnant, breastfeeding or who have a positive pregnancy test at screening or Day
- •Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.
研究组 & 干预措施
Ravulizumab SC Treatment Group
In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by SC maintenance doses of ravulizumab administered via the ravulizumab OBDS on Day 15 and every week (qw) thereafter for a total of 10 weeks of study treatment.
In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.
干预措施: Ravulizumab OBDS (Combination Product)
Ravulizumab SC Treatment Group
In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by SC maintenance doses of ravulizumab administered via the ravulizumab OBDS on Day 15 and every week (qw) thereafter for a total of 10 weeks of study treatment.
In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.
干预措施: Ravulizumab (Biological)
Ravulizumab IV Treatment Group
In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by IV maintenance doses of ravulizumab on Day 15.
In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.
干预措施: Ravulizumab OBDS (Combination Product)
Ravulizumab IV Treatment Group
In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by IV maintenance doses of ravulizumab on Day 15.
In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.
干预措施: Ravulizumab (Biological)
结局指标
主要结局
Ctrough Serum Concentration of Ravulizumab
时间窗: Predose at Day 71
次要结局
- Ctrough Serum Concentration of Ravulizumab at Day 351(Predose at Day 351)
- Free Serum Complement Component 5 (C5) Concentrations at Day 71(Predose at Day 71)
- Free Serum Complement Component 5 (C5) Concentrations at Day 351(Predose at Day 351)
- Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71(Baseline, Day 71)
- Percent Change From Baseline in LDH Levels at Day 351(Baseline, Day 351)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71(Baseline, Day 71)
- Change From Baseline in FACIT-Fatigue Scale Version 4 Score at Day 351(Baseline, Day 351)
- Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71(Baseline, Day 71)
- Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351(Baseline, Day 351)
- Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71(Baseline up to Day 71)
- Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351(Baseline up to Day 351)
- Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71(Baseline up to Day 71)
- Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351(Baseline up to Day 351)
- Percentage of Participants Who Maintained Stabilized Hemoglobin (SHg) up to Day 71(Baseline up to Day 71)
- Percentage of Participants Who Maintained SHg up to Day 351(Baseline up to Day 351)