A Phase II, Double-blind, Placebo-controlled, Randomized, Cross-over, Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema Due to C1-inhibitor Deficiency Type I and II
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Change of the 3-symptom Composite Visual Analogue Scale (VAS-3) Score From Pre-treatment to 4 Hours Post-treatment
研究概览
简要总结
This study evaluates the efficacy of orally administered deucrictibant for the acute treatment of attacks in patients with hereditary angioedema (HAE). Eligible subjects are randomized to one of three single doses of deucrictibant and placebo. The study will compare symptom relief (skin pain, skin swelling, abdominal pain) during HAE attacks and safety of each dose of deucrictibant with placebo.
详细描述
In Part I of the study, patients in non-attack state receive the assigned active single dose of deucrictibant at the study center to assess pharmacokinetics (the way the body absorbs, distributes, and gets rid of the drug) and safety. In Part II of the study, patients self-administer blinded study drug at home to treat three HAE attacks with deucrictibant or placebo (cross-over).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and dated informed consent form
- •Diagnosis of HAE type I or II
- •Documented history of HAE attacks: at least three in the last 4 months, or at least two in the last 2 months prior to screening
- •Reliable access and experience to use standard of care acute attack medications
排除标准
- •Pregnancy or breast-feeding
- •Clinically significant abnormal electrocardiogram
- •Any other systemic disease or significant disease or disorder that would interfere with the patient's safety or ability to participate in the study
- •Use of C1-esterase inhibitor, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy within a defined period prior to enrollment
- •Positive serology for HIV or active infection with hepatitis B virus or hepatitis C virus
- •Abnormal hepatic function
- •Abnormal renal function
- •History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
- •History of documented severe hypersensitivity to any medicinal product
- •Participation in any other investigational drug study within defined period
研究组 & 干预措施
Low dose/placebo
Single low dose of deucrictibant or placebo
干预措施: Deucrictibant (Drug)
Low dose/placebo
Single low dose of deucrictibant or placebo
干预措施: Placebo (Drug)
Medium dose/placebo
Single medium dose of deucrictibant or placebo
干预措施: Deucrictibant (Drug)
Medium dose/placebo
Single medium dose of deucrictibant or placebo
干预措施: Placebo (Drug)
High dose/placebo
Single high dose of deucrictibant or placebo
干预措施: Deucrictibant (Drug)
High dose/placebo
Single high dose of deucrictibant or placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change of the 3-symptom Composite Visual Analogue Scale (VAS-3) Score From Pre-treatment to 4 Hours Post-treatment
时间窗: Assessed from pre-treatment to 4 hours post-treatment
The primary endpoint of the study was the change of the VAS-3 (3-symptom composite visual analogue scale) score from pre-treatment to 4 hours post-treatment. The VAS-3 was calculated as the mean of the VAS scores of the 3 major HAE symptoms: skin swelling, skin pain, and abdominal pain. The VAS scores of the 3 major HAE symptoms (skin swelling, skin pain, and abdominal pain) could range between 0 (No swelling/No pain) and 100 (Extreme swelling/Excruciating pain)
次要结局
- Time to Onset of Symptom Relief by ≥30% Reduction in Visual Analogue Scale (VAS-3) Composite Score From the Pre-treatment Score(Assessed from pre-treatment to 48-hours post-treatment)
- Time to Onset of Almost Complete or Complete Symptom Relief by Visual Analogue Scale (VAS-3)(Assessed from pre-treatment to 48 hours post-treatment)
- Time to a ≥50% Reduction in VAS-3 Composite Score From the Pre-treatment Score(Assessed from pre-treatment to 48 hours post-treatment)
- Change in the Mean Symptom Complex Severity (MSCS) Score From Pre-treatment to 4 Hours Post-treatment(Pre-treatment and 4 hours post-treatment)
- Treatment Outcome Score (TOS) at 4 Hours Post-treatment(4 hours post-treatment)
- Time to Onset of Primary Symptom Relief Assessed by a 30% Reduction in the VAS for the Primary Symptom(Within 48 hours post-treatment)
- Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 12 Hours.(Assessed at 12 hours post study drug treatment)
- Time to First HAE Rescue Medication Use for Study Drug-treated Attacks Within 48 Hours Post-treatment(Assessed at 48 hours post study drug treatment)
- Time to Change in the VAS Score for Skin Pain Score - 30% Reduction(Within 48 hours post treatment)
- Change in Mean Symptom Complex Severity Score From Pre-treatment to 24 Hours Post-treatment(24 hours post-treatment)
- TOS at 24 Hours Post-treatment(Assessed within 24 hours post treatment)
- Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Effectiveness Domain Score(48 hours post-treatment)
- Time to Onset of Primary Symptom Relief by 50% Reduction in VAS Score(Within 48 hours post-treatment)
- Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 24 Hours.(Assessed at 24 hours post-study drug treatment)
- Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 48 Hours(Assessed at 48 hours post-study drug treatment)
- Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Convenience Domain Score(48 hours post-treatment)
- Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Satisfaction Domain Score(48 hours post-treatment)
- Time to Change in the VAS Score for Skin Swelling Score - 30% Reduction(Within 48 hours post-treatment)
- Time to Change in the VAS Score for Abdominal Pain Score - 30% Reduction(Within 48 hours post-treatment)