Title

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

    Phase 3
  • Study Type

    Interventional
  • Study Participants

    19
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.
Study Started
Feb 28
2019
Primary Completion
Nov 15
2019
Study Completion
Jun 30
2021
Anticipated
Results Posted
Mar 04
2021
Last Update
Mar 04
2021

Drug BCX7353 capsules

BCX7353 capsules administered orally once daily

Drug BCX7353 capsules

BCX7353 capsules administered orally once daily

Drug Placebo oral capsule

Matching placebo capsules administered orally once daily

BCX7353 110mg once daily Experimental

BCX7353 capsules administered orally once daily

BCX7353 150mg once daily Experimental

BCX7353 capsules administered orally once daily

Placebo Placebo Comparator

Matching placebo oral capsules administered orally once daily

Criteria

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

Summary

Berotralstat 110mg Once Daily

Berotralstat 150mg Once Daily

Placebo

All Events

Event Type Organ System Event Term Berotralstat 110mg Once Daily Berotralstat 150mg Once Daily Placebo

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.

Berotralstat 110mg Once Daily

1.961
Angioedema event rate per 28 days (Mean)
Standard Deviation: 1.3021

Berotralstat 150mg Once Daily

1.089
Angioedema event rate per 28 days (Mean)
Standard Deviation: 0.9168

Placebo

2.734
Angioedema event rate per 28 days (Mean)
Standard Deviation: 1.6359

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.

Berotralstat 110mg Once Daily

1.988
Angioedema event rate per 28 days (Mean)
Standard Deviation: 1.3422

Berotralstat 150mg Once Daily

1.136
Angioedema event rate per 28 days (Mean)
Standard Deviation: 0.9564

Placebo

2.775
Angioedema event rate per 28 days (Mean)
Standard Deviation: 1.6472

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.

Berotralstat 110mg Once Daily

0.258
Proportion days with angioedema symptoms (Least Squares Mean)
Standard Error: 0.0534

Berotralstat 150mg Once Daily

0.118
Proportion days with angioedema symptoms (Least Squares Mean)
Standard Error: 0.0500

Placebo

0.24
Proportion days with angioedema symptoms (Least Squares Mean)
Standard Error: 0.0536

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.

Berotralstat 110mg Once Daily

-9.47
AE-QoL Total Score Change from baseline (Least Squares Mean)
Standard Error: 6.933

Berotralstat 150mg Once Daily

-15.82
AE-QoL Total Score Change from baseline (Least Squares Mean)
Standard Error: 6.424

Placebo

3.18
AE-QoL Total Score Change from baseline (Least Squares Mean)
Standard Error: 6.832

Total

19
Participants

Age, Continuous

42.1
years (Mean)
Standard Deviation: 12.61

Baseline expert-confirmed angioedema event rate

Race (NIH/OMB)

Sex: Female, Male

Overall Study

Berotralstat 110mg Once Daily

Berotralstat 150mg Once Daily

Placebo

Drop/Withdrawal Reasons

Placebo