A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Two Dose Levels of BCX7353 as an Oral Treatment for the Prevention of Attacks in Subjects With Hereditary Angioedema
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 121
- 试验地点
- 3
- 主要终点
- Part 1: The Rate of Investigator-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168)
研究概览
简要总结
This is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of oral BCX7353 in preventing acute angioedema attacks in patients with Type I and Type II HAE.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Only Part 1 and Part 2 were blinded. As part 3 was open-label, no blinding was used
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A clinical diagnosis of hereditary angioedema Type 1 or Type 2, defined as having a C1-INH functional level and a C4 level below the lower limit of the normal (LLN) reference range, as assessed during the Screening period.
- •Subject weight of ≥ 40 kg
- •Access to and ability to use one or more acute medications approved by the relevant competent authority for the treatment of acute attacks of HAE
- •Subjects must be medically appropriate for on-demand treatment as the sole medicinal management for their HAE during the study.
- •Subjects must have a specified number of investigator-confirmed attacks during the run-in period of a maximum of 56 days from the Screening visit.
- •Acceptable effective contraception
- •Written informed consent
排除标准
- •Pregnancy or breast-feeding
- •Any clinically significant medical condition or medical history that, in the opinion of the Investigator or Sponsor, would interfere with the subject's safety or ability to participate in the study
- •Any laboratory parameter abnormality that, in the opinion of the Investigator, is clinically significant and relevant for this study
- •Severe hypersensitivity to multiple medicinal products or severe hypersensitivity/ anaphylaxis with unclear etiology
- •Use of C1-INH within 14 days or use of androgens or tranexamic acid within 28 days prior to the Screening visit for prophylaxis of HAE attacks, or initiation of these drugs during the study
- •Current participation in any other investigational drug study or received another investigational drug within 30 days of the Screening visit
- •Prior enrollment in a BCX7353 study
研究组 & 干预措施
BCX7353 110 mg once daily
BCX7353 administered as oral capsules once daily
干预措施: BCX7353 capsules (Drug)
BCX7353 150 mg once daily
BCX7353 administered as oral capsules once daily
干预措施: BCX7353 capsules (Drug)
Placebo
Matching placebo administered as oral capsules once daily
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Part 1: The Rate of Investigator-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168)
时间窗: 24 weeks
Treatment comparisons between each berotralstat dose and placebo in the rate of investigator-confirmed HAE attacks during the Part 1 dosing period were analyzed using a negative binomial model. The number of investigator-confirmed attacks was included as the dependent variable, the treatment was included as a fixed effect, the stratification variable (baseline attack rate) was included as a covariate, and the logarithm of duration on treatment was included as an offset variable. The estimated attack rate for each treatment group, the treatment differences expressed as the attack rate ratio (berotralstat over placebo rate ratio), and the associated 95% confidence intervals (CIs) were provided from the negative binomial model.
Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE
时间窗: Part 2: 24 weeks (Days 169 to 337). Part 3: 48 weeks (Days 338 to 674).
The safety data was assessed for the safety population, for subjects who entered Part 2 and Part 3, and includes TEAEs that began in Part 2 or 3, respectively, for these subjects. Safety data for Part 2 and Part 3 is combined to clearly show TEAEs occurring in subjects as the proceeded through the 2 study parts. TEAEs are defined as AEs that occurred on or after first dose of study treatment, whether in Part 1 or 2, and were assigned to the relevant treatment depending on when the TEAE began (Part 2 or Part 3 treatment). No statistical analysis was performed on this safety data.
次要结局
- Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks(24 weeks)
- Part 2: To Assess the Effectiveness of Berotralstat Over a 24- to 48 Week Period(24 weeks (Days 169 to 337))
- Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period(Day 8 through to 24 weeks (or or the last dose date/time in Part 1 + 24 hours for subjects who discontinued drug in Part 1))
- Part 1: Change From Baseline in Angioedema Quality of Life Questionnaire at Week 24 (Total Score)(Baseline and 24 weeks)
- To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks(Up to 144 weeks)
- To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks(Up to 144 weeks)