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

NCT03873116 | Completed Phase 3 Results DMC

• 1 other identifier: BCX7353-301
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 10

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.

Conditions

Hereditary Angioedema, HAE

Keywords

BCX7353

Outcome Measures

Primary Outcomes (3)

• 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.

  24 weeks

• Part 2: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE

  The safety data was assessed for the safety population for subjects who entered Part 2, and includes TEAEs that occurred in Part 1 and Part 2 for these subjects with a data cut-off date of 10-April-2020. TEAEs are defined as AEs that occurred on or after first dose of study treatment, whether in Part 1 or 2, and were assigned to the relevant treatment depending on when the TEAE began (Part 1 or Part 2 treatment). TEAEs were assessed for severity (graded) using the Division of Microbiology and Infectious Disease (DMID) criteria for grading AEs. TEAEs not covered by the DMID criteria were assessed as Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3) or Life-threatening (Grade 4).

  Part 1: 24 weeks (Week 0 to 24 to 52), Part 2: 28 weeks (Week 24 to 52)

• Part 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat Administered QD Over a 52- to up to 104-week Administration Period in Subjects With HAE.

  The safety data was assessed for the safety population for subjects who entered Part 3, and includes TEAEs that occurred in Part 3 for these subjects.

  Part 3: Week 52 to up to Week 104.

Secondary Outcomes (8)

• Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks.

  24 weeks

• Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period

  Day 8 through to 24 weeks

• Part 1: Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire at Week 24 (Total Score)

  Baseline and 24 weeks

• Part 2: To Assess the Effectiveness of Berotralstat Over a 24- to 52-week Period

  28 weeks (Week 24 to 52)

• Part 2: To Evaluate QoL Following Berotralstat Administration Over a 24- to 52-week Period.

  28 Weeks (Week 24 to 52)

Study Arms (3)

BCX7353 110mg once daily

EXPERIMENTAL

BCX7353 capsules administered orally once daily

Drug: BCX7353 capsules

BCX7353 150mg once daily

EXPERIMENTAL

BCX7353 capsules administered orally once daily

Drug: BCX7353 capsules

Placebo

PLACEBO COMPARATOR

Matching placebo oral capsules administered orally once daily

Drug: Placebo oral capsule

Interventions

BCX7353 capsules DRUG

BCX7353 capsules administered orally once daily

BCX7353 110mg once daily

Placebo oral capsule DRUG

Matching placebo capsules administered orally once daily

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BioCryst Pharmaceuticals: lead

Study Sites (10)

Study Site

Chiba, Japan

Location

Study Site

Gunma, Japan

Location

Study Site

Hokkaido, Japan

Location

Study Site

Nagoya, Japan

Location

Study Site

Osaka, Japan

Location

Study Center

Saga, Japan

Location

Study Site

Saitama, Japan

Location

Study Site

Shimane, Japan

Location

Study Site

Shizuoka, Japan

Location

Study Site

Tokyo, Japan

Location

Related Publications (4)

• Honda D, Hide M, Fukuda T, Koga K, Morita E, Moriwaki S, Sasaki Y, Suzuki Y, Collis P, Johnston DT, Tomita D, Desai B, Ohsawa I. Berotralstat for long-term prophylaxis of hereditary angioedema in Japan: Parts 2 and 3 of the randomized APeX-J Phase III trial. World Allergy Organ J. 2024 Mar 2;17(3):100882. doi: 10.1016/j.waojou.2024.100882. eCollection 2024 Mar.

  PMID: 38445295 DERIVED

• Farkas H, Balla Z. A review of berotralstat for the treatment of hereditary angioedema. Expert Rev Clin Immunol. 2023 Feb;19(2):145-153. doi: 10.1080/1744666X.2023.2150611. Epub 2022 Nov 29.

  PMID: 36408587 DERIVED

• 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.

  PMID: 36326435 DERIVED

• 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.

  PMID: 33247955 DERIVED

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

berotralstat

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Results Point of Contact

• Title: Study Director
• Organization: BioCryst Pharmaceuticals Inc

clinicaltrials@biocryst.com

+1 919-859-1302

Study Officials

• Isao Ohsawa

  Saiyu Soka Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: March 13, 2019
• Study Start: December 27, 2018
• Primary Completion: July 8, 2021
• Study Completion: July 8, 2021
• Last Updated: July 19, 2024
• Results First Posted: March 4, 2021

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

JP (10)