A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Complement Inhibitor-Naïve Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 272
- 试验地点
- 121
- 主要终点
- Percentage Of Participants Who Achieved Transfusion Avoidance (TA)
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 had never been treated with a complement inhibitor (treatment-naïve).
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 26-week Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants will receive ravulizumab for up to 5 years.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥18 years of age.
- •PNH diagnosis confirmed by documented by high-sensitivity flow cytometry.
- •Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia (hemoglobin <10 gram/deciliter), history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of packed red blood cells (pRBC) transfusion due to PNH.
- •Lactate dehydrogenase (LDH) level ≥1.5 times the upper limit of normal at screening.
- •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
- •Treatment with a complement inhibitor at any time.
- •History of bone marrow transplantation.
- •Body weight <40 kg.
- •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.
- •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). Eligibility Criteria For Roll-over Cohort:
- •All participants regardless of age, who are currently receiving ALXN1210 IV in an ongoing ALXN1210 study in patients with PNH
- •Participants must be willing and able to give written informed consent and to comply with all Extension study visits and procedures, including the use of any data collection device(s) to directly record patient data
- •Females of childbearing potential and male patients with female partners of childbearing potential must use highly effective contraception continuing until at least 8 months after the last dose of ravulizumab.
结局指标
主要结局
Percentage Of Participants Who Achieved Transfusion Avoidance (TA)
时间窗: Baseline through Day 183
Transfusion avoidance was defined as the percentage of participants who remained transfusion free and did not require a transfusion per protocol-specified guidelines through Day 183.
Proportion Of Participants With Normalization Of Lactate Dehydrogenase (LDH) Levels
时间窗: Day 29 through Day 183
LDH is an indicator of intravascular hemolysis that occurs in participants with paroxysmal nocturnal hemoglobinuria (PNH). A decrease in LDH from above the upper limit of normal (ULN) to below the ULN indicates reduction (improvement) in hemolysis. Normalization of LDH levels (LDH-N) was LDH levels less than or equal to 1 x ULN, from Day 29 through Day 183. The ULN for LDH is 246 U/L.
次要结局
- Percent Change From Baseline In LDH Levels(Baseline, Day 183)
- Percentage Of Participants With Breakthrough Hemolysis (BTH)(Baseline through Day 183)
- Change From Baseline In Quality Of Life As Assessed By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue(Baseline, Day 183)
- Percentage Of Participants With Stabilized Hemoglobin Levels(Baseline through Day 183)