search
Back to results

Study to Evaluate the Efficacy and Safety of BCX7353 as an Oral Treatment for the Prevention of HAE Attacks in Japan (APeX-J)

Primary Purpose

Hereditary Angioedema, HAE

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
BCX7353 capsules
BCX7353 capsules
Placebo oral capsule
Sponsored by
BioCryst Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hereditary Angioedema, HAE focused on measuring BCX7353

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Study Site
  • Study Site
  • Study Site
  • Study Site
  • Study Site
  • Study Center
  • Study Site
  • Study Site
  • Study Site
  • Study Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

BCX7353 110mg once daily

BCX7353 150mg once daily

Placebo

Arm Description

BCX7353 capsules administered orally once daily

BCX7353 capsules administered orally once daily

Matching placebo oral capsules administered orally once daily

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
March 11, 2019
Last Updated
January 12, 2023
Sponsor
BioCryst Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT03873116
Brief Title
Study to Evaluate the Efficacy and Safety of BCX7353 as an Oral Treatment for the Prevention of HAE Attacks in Japan
Acronym
APeX-J
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
February 28, 2019 (Actual)
Primary Completion Date
November 15, 2019 (Actual)
Study Completion Date
July 8, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioCryst Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema, HAE
Keywords
BCX7353

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BCX7353 110mg once daily
Arm Type
Experimental
Arm Description
BCX7353 capsules administered orally once daily
Arm Title
BCX7353 150mg once daily
Arm Type
Experimental
Arm Description
BCX7353 capsules administered orally once daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo oral capsules administered orally once daily
Intervention Type
Drug
Intervention Name(s)
BCX7353 capsules
Intervention Description
BCX7353 capsules administered orally once daily
Intervention Type
Drug
Intervention Name(s)
BCX7353 capsules
Intervention Description
BCX7353 capsules administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
Matching placebo capsules administered orally once daily
Primary Outcome Measure Information:
Title
Part 1: The Rate of Expert-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168)
Description
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.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks.
Description
Assessment of number and proportion of days subjects had angioedema symptoms from expert-confirmed angioedema events during Part 1.
Time Frame
24 weeks
Title
Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period
Description
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.
Time Frame
Day 8 through to 24 weeks
Title
Part 1: Change From Baseline in Angioedema Quality of Life (AE- QoL) Questionnaire at Week 24 (Total Score)
Description
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.
Time Frame
Baseline and 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Isao Ohsawa
Organizational Affiliation
Saiyu Soka Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Study Site
City
Chiba
Country
Japan
Facility Name
Study Site
City
Gunma
Country
Japan
Facility Name
Study Site
City
Hokkaido
Country
Japan
Facility Name
Study Site
City
Nagoya
Country
Japan
Facility Name
Study Site
City
Osaka
Country
Japan
Facility Name
Study Center
City
Saga
Country
Japan
Facility Name
Study Site
City
Saitama
Country
Japan
Facility Name
Study Site
City
Shimane
Country
Japan
Facility Name
Study Site
City
Shizuoka
Country
Japan
Facility Name
Study Site
City
Tokyo
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36326435
Citation
Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
Results Reference
derived
PubMed Identifier
33247955
Citation
Ohsawa I, Honda D, Suzuki Y, Fukuda T, Kohga K, Morita E, Moriwaki S, Ishikawa O, Sasaki Y, Tago M, Chittick G, Cornpropst M, Murray SC, Dobo SM, Nagy E, Van Dyke S, Reese L, Best JM, Iocca H, Collis P, Sheridan WP, Hide M. Oral berotralstat for the prophylaxis of hereditary angioedema attacks in patients in Japan: A phase 3 randomized trial. Allergy. 2021 Jun;76(6):1789-1799. doi: 10.1111/all.14670. Epub 2020 Dec 23.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs