LEVP2005-1/Part A: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) for the Treatment of HAE in Acute Attacks
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 83
- 试验地点
- 37
- 主要终点
- Time to Beginning of Substantial Relief of the Defining Symptom
研究概览
简要总结
The study objective was to determine the safety and efficacy of C1INH-nf for the treatment of acute HAE attacks.
详细描述
Randomized subjects treated for a qualifying attack were eligible to receive rescue dosing with 1,000 U of C1INH-nf if they did not achieve beginning of substantial relief of the defining symptom within 4 hours after initial treatment with blinded study drug, or if at any time the attack progressed to include airway compromise. A second 1,000 U rescue dose was permitted 60 minutes after the initial rescue dose, if necessary.
The study design also allowed for administration of open-label C1INH-nf for laryngeal angioedema attacks, which were non-randomizable events due to the presence of or potential for airway compromise (immediate 1,000 U dose of C1INH-nf, repeated after 60 minutes, if necessary). In addition, subjects were eligible to receive open-label C1INH-nf (1,000 U single dose) prior to emergency surgical (non-cosmetic) procedures.
A total of 83 subjects were enrolled in the study. Seventy-one (71) subjects experienced qualifying attacks and were randomized to blinded study drug (36 C1INH-nf, 35 placebo); only the 71 randomized subjects were analyzed for efficacy. An additional 12 subjects were never randomized but received open-label C1INH-nf for treatment of laryngeal angioedema and/or prior to emergency surgical procedures. Of the 35 subjects randomized to placebo, 23 also received C1INH-nf (eg, rescue, open-label). In total, 83 subjects received at least 1 dose of study drug and were analyzed for safety; 71 subjects were exposed to C1INH-nf (59 randomized, 12 open-label only) and 12 subjects were exposed only to placebo.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented HAE
- •Normal C1q level
排除标准
- •Low C1q level
- •B-cell malignancy
- •Presence of anti-C1INH autoantibody
- •History of allergic reaction to C1INH or other blood products
- •Narcotic addiction
- •Current participation in any other investigational drug study or within the past 30 days
- •Participation in a C1 esterase inhibitor trial, or received blood or a blood product in the past 90 days
- •Pregnancy or lactation
- •Any clinically significant medical condition, such as renal failure, that in the opinion of the investigator would interfere with the subject's ability to participate in the study
研究组 & 干预措施
C1INH-nf
1,000 Units (U) of C1INH-nf administered intravenously (IV). If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
干预措施: C1 esterase inhibitor [human] (C1INH-nf) (Biological)
Placebo
Matching placebo (saline) administered IV. If there was no response to treatment 60 minutes after the first dose, a second placebo (saline) dose could be administered.
干预措施: Placebo (saline) (Drug)
结局指标
主要结局
Time to Beginning of Substantial Relief of the Defining Symptom
时间窗: Within 4 hours after initial treatment
Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug or until substantial relief of the defining symptom was achieved. Substantial relief was defined as 3 consecutive assessments of improvement of the defining symptom. Beginning of substantial relief was considered the first of the 3 consecutive assessments.
次要结局
- Number of Subjects With Beginning of Substantial Relief of the Defining Symptom(Within 4 hours after initial treatment)
- Antigenic C1 Inhibitor (C1INH) Serum Levels(Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion)
- Time to Complete Resolution of the HAE Attack(72 hours)
- Functional C1INH Serum Levels(Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion)
- Complement C4 Serum Levels(Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion)