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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03873116
Recruitment Status : Active, not recruiting
First Posted : March 13, 2019
Results First Posted : March 4, 2021
Last Update Posted : March 4, 2021
Information provided by (Responsible Party):
BioCryst Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Hereditary Angioedema, HAE Drug: BCX7353 capsules Drug: Placebo oral capsule Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
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
Actual Study Start Date : February 28, 2019
Actual Primary Completion Date : November 15, 2019
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BCX7353 110mg once daily
BCX7353 capsules administered orally once daily
Drug: BCX7353 capsules
BCX7353 capsules administered orally once daily

Experimental: BCX7353 150mg once daily
BCX7353 capsules administered orally once daily
Drug: BCX7353 capsules
BCX7353 capsules administered orally once daily

Placebo Comparator: Placebo
Matching placebo oral capsules administered orally once daily
Drug: Placebo oral capsule
Matching placebo capsules administered orally once daily

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks. [ Time Frame: 24 weeks ]
    Assessment of number and proportion of days subjects had angioedema symptoms from expert-confirmed angioedema events during Part 1.

  2. Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period [ Time Frame: Day 8 through to 24 weeks ]
    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.

  3. Part 1: Change From Baseline in Angioedema Quality of Life (AE- QoL) Questionnaire at Week 24 (Total Score) [ Time Frame: Baseline and 24 weeks ]
    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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03873116

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Study Site
Chiba, Japan
Study Site
Gunma, Japan
Study Site
Hokkaido, Japan
Study Site
Nagoya, Japan
Study Site
Osaka, Japan
Study Center
Saga, Japan
Study Site
Saitama, Japan
Study Site
Shimane, Japan
Study Site
Shizuoka, Japan
Study Site
Tokyo, Japan
Sponsors and Collaborators
BioCryst Pharmaceuticals
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Principal Investigator: Isao Ohsawa Saiyu Soka Hospital
  Study Documents (Full-Text)

Documents provided by BioCryst Pharmaceuticals:
Study Protocol  [PDF] August 7, 2020
Statistical Analysis Plan  [PDF] November 4, 2019

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: BioCryst Pharmaceuticals Identifier: NCT03873116    
Other Study ID Numbers: BCX7353-301
First Posted: March 13, 2019    Key Record Dates
Results First Posted: March 4, 2021
Last Update Posted: March 4, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioCryst Pharmaceuticals:
Additional relevant MeSH terms:
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Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Immune System Diseases
Hereditary Complement Deficiency Diseases
Primary Immunodeficiency Diseases
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action