Study to Evaluate the Efficacy and Safety of BCX7353 as an Oral Treatment for the Prevention of HAE Attacks in Japan

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hereditary Angioedema, HAE

Intervention / Treatment
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* Drug: BCX7353 capsules
* Drug: BCX7353 capsules
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 Key Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCX7353 110mg once daily<br>BCX7353 capsules administered orally once daily | Drug: BCX7353 capsules<br>* BCX7353 capsules administered orally once daily<br>|
| Experimental: BCX7353 150mg once daily<br>BCX7353 capsules administered orally once daily | Drug: BCX7353 capsules<br>* BCX7353 capsules administered orally once daily<br>|
| Placebo Comparator: Placebo<br>Matching placebo oral capsules administered orally once daily | Drug: Placebo oral capsule<br>* Matching placebo capsules administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: The Rate of Expert-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168) | 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. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks. | Assessment of number and proportion of days subjects had angioedema symptoms from expert-confirmed angioedema events during Part 1. | 24 weeks | 
| Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period | The rate of expert-confirmed angioedema events for the effective treatment period gives an analysis of the efficacy of active treatment after berotralstat had reached steady-state concentrations, given the effective half-life of 150 mg berotralstat in Study BCX7353-106 (Study 106) of 89 hours. | Day 8 through to 24 weeks | 
| Part 1: Change From Baseline in Angioedema Quality of Life (AE- QoL) Questionnaire at Week 24 (Total Score) | Change in Quality of Life, on a 1-100 scale, where higher scores indicate more impairment and a decrease (change with a negative value) in AE-QoL questionnaire scores indicates an improvement in the subject's QoL. The minimum clinically important difference (MCID) for the AE-QoL questionnaire is -6 (total score). The AE-QoL is only validated for adults; however, data were collected on all adult and adolescent study subjects. | Baseline and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCX7353