- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03873116
Study to Evaluate the Efficacy and Safety of BCX7353 as an Oral Treatment for the Prevention of HAE Attacks in Japan (APeX-J)
January 12, 2023 updated by: BioCryst Pharmaceuticals
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
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 Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
19
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Chiba, Japan
- Study Site
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Gunma, Japan
- Study Site
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Hokkaido, Japan
- Study Site
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Nagoya, Japan
- Study Site
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Osaka, Japan
- Study Site
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Saga, Japan
- Study Center
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Saitama, Japan
- Study Site
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Shimane, Japan
- Study Site
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Shizuoka, Japan
- Study Site
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Tokyo, Japan
- Study Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
12 years and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BCX7353 110mg once daily
BCX7353 capsules administered orally once daily
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BCX7353 capsules administered orally once daily
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Experimental: BCX7353 150mg once daily
BCX7353 capsules administered orally once daily
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BCX7353 capsules administered orally once daily
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Placebo Comparator: Placebo
Matching placebo oral capsules administered orally once daily
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Matching placebo capsules administered orally once daily
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What is the study measuring?
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)
Time Frame: 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.
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24 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks.
Time Frame: 24 weeks
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Assessment of number and proportion of days subjects had angioedema symptoms from expert-confirmed angioedema events during Part 1.
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24 weeks
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Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period
Time Frame: Day 8 through to 24 weeks
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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.
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Day 8 through to 24 weeks
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Part 1: Change From Baseline in Angioedema Quality of Life (AE- QoL) Questionnaire at Week 24 (Total Score)
Time Frame: Baseline and 24 weeks
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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.
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Baseline and 24 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Isao Ohsawa, Saiyu Soka Hospital
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 28, 2019
Primary Completion (Actual)
November 15, 2019
Study Completion (Actual)
July 8, 2021
Study Registration Dates
First Submitted
March 11, 2019
First Submitted That Met QC Criteria
March 11, 2019
First Posted (Actual)
March 13, 2019
Study Record Updates
Last Update Posted (Estimate)
January 16, 2023
Last Update Submitted That Met QC Criteria
January 12, 2023
Last Verified
January 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Skin Diseases
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Hypersensitivity, Immediate
- Genetic Diseases, Inborn
- Skin Diseases, Vascular
- Hypersensitivity
- Urticaria
- Hereditary Complement Deficiency Diseases
- Primary Immunodeficiency Diseases
- Angioedema
- Angioedemas, Hereditary
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Berotralstat
Other Study ID Numbers
- BCX7353-301
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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