A Phase III Randomized, Double-Blind,Placebo-Controlled, Multicenter Study of Icatibant for Subcutaneous Injection in Patients With Acute Attacks of Hereditary Angioedema (HAE)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 98
- 试验地点
- 64
- 主要终点
- Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient
研究概览
简要总结
This study is being conducted to evaluate the efficacy and safety of icatibant compared to placebo in patients experiencing acute attacks of hereditary angioedema (HAE).
详细描述
This Phase III study consisted of two parts: A controlled phase and an open label extension (OLE) phase.
The controlled phase describes the double blind part of the study and was intended to evaluate the efficacy and safety of icatibant compared with placebo for the first treated cutaneous and/or abdominal attack.
Patients with moderate to severe abdominal or cutaneous attacks were randomized to receive a single, blinded, subcutaneous injection of icatibant (30 mg) or placebo. After a protocol amendment, patients with mild to moderate laryngeal HAE attacks were also randomized to receive a single, blinded subcutaneous injection of icatibant (30 mg) or placebo in order to obtain blinded, controlled efficacy and safety data for this subset of subjects. Patients experiencing severe laryngeal attacks (post-amendment) or mild to severe laryngeal attacks (pre-amendment) were to receive open-label icatibant.
After treatment of the first attack in the controlled phase, patients were eligible to enter the OLE phase. In the OLE phase, patients who experienced angioedema attacks severe enough to warrant treatment were to be treated with s.c. icatibant as appropriate until the study was discontinued or the product was commercially available.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Each patient must meet the following criteria to be enrolled in this study.
- •The patient is ≥18 years old at the time of informed consent.
- •The patient has a documented diagnosis of HAE type I or II. The diagnosis will be confirmed either by documented decreased C4 levels and/or immunogenic or functional C1-INH deficiency results (<50% of normal levels) consistent with HAE types I and II or by medical history.
- •The current HAE attack must be in the cutaneous, abdominal and/or laryngeal (inclusive of laryngeal and pharyngeal) areas.
- •Cutaneous or abdominal HAE attacks must be moderate to very severe as determined by investigator global assessment at pre-treatment assessments
- •The patient must report at least 1 VAS score ≥ 30mm
- •The patient commences treatment within 6 hours of the attack becoming at least mild (laryngeal) or moderate (non-laryngeal) in severity, but not more than 12 hours after the onset of the attack.
- •Women of childbearing potential must have a negative urine pregnancy test and must use appropriate methods to prevent pregnancy during their participation in the study.
排除标准
- •Patients who meet any of the following criteria will be excluded from the study.
- •The patient has a diagnosis of angioedema other than HAE type I or II.
- •The patient has received previous treatment with icatibant.
- •The patient has participated in a clinical trial and has received treatment with another investigational medicinal product within the past 30 days.
- •The patient has received treatment with any pain medication since the onset of the current angioedema attack.
- •The patient has received replacement therapy (fresh frozen plasma [FFP], C1-INH products) less than 5 days (120 hours) from the onset of the current angioedema attack.
- •The patient is receiving treatment with angiotensin converting enzyme (ACE) inhibitors.
- •Evidence of coronary artery disease based on medical history or screening examination in particular unstable angina pectoris or severe coronary heart disease;
- •The patient has a serious concomitant illness or condition that, in the opinion of the Investigator, would be a contraindication for participation in the trial.
- •The patient is pregnant or breastfeeding.
研究组 & 干预措施
Placebo
Single subcutaneous injection of matching placebo
干预措施: Placebo (Drug)
Icatibant
Single subcutaneous injection of icatibant, 30 mg
干预措施: Icatibant (Drug)
结局指标
主要结局
Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient
时间窗: Up to 120 hours post-dose
Time to onset of symptom relief was calculated from study drug administration to onset of symptom relief, where onset of symptom relief was defined as the earliest of 3 consecutive measurements in which there was a 50% reduction from pretreatment in composite VAS score. Composite VAS score comprised 3 symptoms, including skin swelling, skin pain, and abdominal pain, for cutaneous and abdominal attacks and 5 symptoms, including skin swelling, skin pain, abdominal pain, difficulty swallowing, and voice change, for laryngeal attacks. Subjects who did not achieve symptom relief within the observation period were censored at the last observation time.
次要结局
- Time to Almost Complete Symptom Relief(Up to 120 Hours post treatment)
- Time to Subject-Assessed Initial Symptom Improvement(Up to 120 hours post-dose)
- Time to Investigator-Assessed Initial Symptom Improvement(Up to 120 hours post-dose)
- Time to Onset of Primary Symptom Relief(Up to 120 hours post-dose)