A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 202
- 试验地点
- 1
- 主要终点
- Percent Change In Lactate Dehydrogenase Levels From Baseline To Day 183
研究概览
简要总结
The primary purpose of this study was to assess the noninferiority of ravulizumab compared to eculizumab in adult participants with PNH who were clinically stable after having been treated with eculizumab for at least 6 months.
详细描述
The study consisted of a 4-week Screening Period and a 26-week Randomized Treatment Period (Primary Evaluation Period). After completion of the Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants will receive ravulizumab for up to 4 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 6 months prior to Day
- •Lactate dehydrogenase level ≤1.5 times the upper limit of normal (ULN) at screening.
- •PNH diagnosis confirmed by documented by high-sensitivity flow cytometry.
- •Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
- •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
- •History of bone marrow transplantation.
- •Body weight <40 kilograms at screening.
- •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 bleeding, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, or coexisting chronic anemia unrelated to PNH).
- •Female participants 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 treatment 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
On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 milligrams (mg). Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127.
After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants will receive weight-based doses of ravulizumab for up to 4 years.
干预措施: Ravulizumab (Biological)
Eculizumab
Participants received 900 mg of eculizumab every 2 weeks (q2w) for 26 weeks.
After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants will receive weight-based doses of ravulizumab for up to 4 years.
干预措施: Ravulizumab (Biological)
Eculizumab
Participants received 900 mg of eculizumab every 2 weeks (q2w) for 26 weeks.
After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants will receive weight-based doses of ravulizumab for up to 4 years.
干预措施: Eculizumab (Biological)
结局指标
主要结局
Percent Change In Lactate Dehydrogenase Levels From Baseline To Day 183
时间窗: Baseline, Day 183
Lactate dehydrogenase (LDH) is an indicator of intravascular hemolysis that occurs in participants with paroxysmal nocturnal hemoglobinuria. A decrease in LDH indicates reduction (improvement) in hemolysis. Baseline was defined as the average of all available on-study assessments prior to the first study drug infusion. The percent change in LDH was analyzed using a mixed-effect model for repeated measures (MMRM) with the fixed, categorical effects of treatment, study visit, and study visit by treatment group interaction, as well as the continuous, fixed covariate of baseline LDH and the stratification randomization indicator of packed red blood cells transfusion history (yes/no within 12 months prior to Day 1).
次要结局
- Number Of Participants With Breakthrough Hemolysis Through Day 183(Baseline through Day 183)
- Change From Baseline To Day 183 In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Scores(Baseline, Day 183)
- Percentage Of Participants Who Achieved Transfusion Avoidance Through Day 183(Baseline through Day 183)
- Percentage Of Participants With Stabilized Hemoglobin Levels Through Day 183(Baseline through Day 183)
- Number Of Participants With Breakthrough Hemolysis Through End of Study(Baseline through end of study (up to 4 years))
- Percentage Of Participants Who Achieved Transfusion Avoidance Through End of Study(Baseline through end of study (up to 4 years))
- Percentage Of Participants With Stabilized Hemoglobin Levels Through End of Study(Baseline through end of study (up to 4 years))
- Change From Baseline To End of Study In FACIT-Fatigue Scores Through End of Study(Baseline, End of Study (up to 4 years))