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Efficacy and Safety Study of BCX7353 as an Oral Treatment for the Prevention of Attacks in HAE (APeX-2)

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.
 
ClinicalTrials.gov Identifier: NCT03485911
Recruitment Status : Completed
First Posted : April 3, 2018
Results First Posted : March 2, 2021
Last Update Posted : January 17, 2023
Sponsor:
Information provided by (Responsible Party):
BioCryst Pharmaceuticals

Study Description
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Brief Summary:
This is a phase 3, multicenter, 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.

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 121 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 6, 2018
Actual Primary Completion Date : April 10, 2019
Actual Study Completion Date : April 6, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: BCX7353 110 mg once daily
BCX7353 administered as oral capsules once daily
 Drug: BCX7353 capsules
BCX7353 oral capsules administered once daily
Other Name: Berotralstat
Experimental: BCX7353 150 mg once daily
BCX7353 administered as oral capsules once daily
 Drug: BCX7353 capsules
BCX7353 oral capsules administered once daily
Other Name: Berotralstat
Placebo Comparator: Placebo
Matching placebo administered as oral capsules once daily
 Drug: Placebo oral capsule
Matching oral capsules administered once daily


Outcome Measures
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Primary Outcome Measures :
  1. Part 1: The Rate of Investigator-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168) [ Time Frame: 24 weeks ]
    Treatment comparisons between each berotralstat dose and placebo in the rate of investigator confirmed HAE attacks during the Part 1 dosing period were analyzed using a negative binomial model. The number of investigator-confirmed attacks was included as the dependent variable, the treatment was included as a fixed effect, the stratification variable (baseline attack rate) was included as a covariate, and the logarithm of duration on treatment was included as an offset variable. The estimated attack rate for each treatment group, the treatment differences expressed as the attack rate ratio (berotralstat over placebo rate ratio), and the associated 95% confidence intervals (CIs) were provided from the negative binomial model.


Secondary Outcome Measures :
  1. Part 1: Change From Baseline in Angioedema Quality of Life 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.

  2. Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks [ Time Frame: 24 weeks ]
    Assessment of proportion of days subjects had angioedema symptoms from expert-confirmed HAE attacks during Part 1.

  3. Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period [ Time Frame: Day 8 through to 24 weeks (or or the last dose date/time in Part 1 + 24 hours for subjects who discontinued drug in Part 1) ]
    The rate of expert-confirmed HAE attacks 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.


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

Key Inclusion Criteria:

  • A clinical diagnosis of hereditary angioedema 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.
  • Subject weight of ≥ 40 kg
  • 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 investigator-confirmed attacks during the run-in period of a maximum 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
Contacts and Locations
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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 ClinicalTrials.gov identifier (NCT number): NCT03485911


Locations
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Sponsors and Collaborators
BioCryst Pharmaceuticals
Investigators
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Principal Investigator: Bruce Zuraw, MD UC San Diego School of Medicine, US HAE Angioedema Center
  Study Documents (Full-Text)

Documents provided by BioCryst Pharmaceuticals:
Study Protocol  [PDF] February 10, 2020
Statistical Analysis Plan  [PDF] January 29, 2019

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03485911    
Other Study ID Numbers: BCX7353-302
First Posted: April 3, 2018    Key Record Dates
Results First Posted: March 2, 2021
Last Update Posted: January 17, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioCryst Pharmaceuticals:
BCX7353
Berotralstat
Additional relevant MeSH terms:
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Angioedema
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
 Hereditary Complement Deficiency Diseases
Primary Immunodeficiency Diseases
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Berotralstat
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action