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
- 19
- 试验地点
- 2
- 主要终点
- Part 1: The Rate of Expert-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, multi-center, 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 who live in Japan.
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)
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 (HAE) 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.
- •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 expert-confirmed attacks during the run-in period 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 110mg once daily
BCX7353 capsules administered orally once daily
干预措施: BCX7353 capsules (Drug)
BCX7353 150mg once daily
BCX7353 capsules administered orally once daily
干预措施: BCX7353 capsules (Drug)
Placebo
Matching placebo oral capsules administered orally once daily
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Part 1: The Rate of Expert-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168)
时间窗: 24 weeks
The angioedema event rate and the treatment comparisons between each berotralstat dose and placebo in the rate of expert-confirmed angioedema events during the entire dosing period was analyzed using a negative binomial regression model. The number of expert-confirmed angioedema events was included as the dependent variable, the treatment was included as a fixed effect, the stratification variable (baseline monthly angioedema event rate) and study (for the combined study analysis) were included as covariates, and the logarithm of duration on treatment was included as an offset variable. The estimated rate of angioedema events for each treatment group, the treatment differences expressed as the angioedema event rate ratio (berotralstat) over placebo rate ratio), and their associated 95% confidence intervals (CIs) were provided from the negative binomial regression model.
Part 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat Administered QD Over a 52- to up to 104-week Administration Period in Subjects With HAE.
时间窗: Part 3: Week 52 to up to Week 104.
The safety data was assessed for the safety population for subjects who entered Part 3, and includes TEAEs that occurred in Part 3 for these subjects.
Part 2: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE
时间窗: Part 1: 24 weeks (Week 0 to 24 to 52), Part 2: 28 weeks (Week 24 to 52)
The safety data was assessed for the safety population for subjects who entered Part 2, and includes TEAEs that occurred in Part 1 and Part 2 for these subjects with a data cut-off date of 10-April-2020. 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 1 or Part 2 treatment). TEAEs were assessed for severity (graded) using the Division of Microbiology and Infectious Disease (DMID) criteria for grading AEs. TEAEs not covered by the DMID criteria were assessed as Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3) or Life-threatening (Grade 4).
次要结局
- Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks.(24 weeks)
- Part 1: Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire at Week 24 (Total Score)(Baseline and 24 weeks)
- Part 3: To Assess the Effectiveness of Berotralstat Over a 52- to up to 104-week Administration Period(52 weeks (Week 52 to 104))
- Part 3: To Evaluate Subject's Satisfaction With Berotralstat During 52- to 104-week Administration Period(52 Weeks (Week 52 to 104))
- Part 2: To Assess the Effectiveness of Berotralstat Over a 24- to 52-week Period(28 weeks (Week 24 to 52))
- Part 2: To Evaluate QoL Following Berotralstat Administration Over a 24- to 52-week Period.(28 Weeks (Week 24 to 52))
- Part 3: To Evaluate QoL Following Berotralstat Administration Over a 52- to up to 104-week Period(52 Weeks (Week 52 to 104))
- Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period(Day 8 through to 24 weeks)