Clinical trial NCT03873116: Study to Evaluate the Efficacy and Safety of BCX7353 as an Oral Treatment for the Prevention of HAE Attacks in Japan
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema, HAE
Keywords: BCX7353
Lead sponsor: BioCryst Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-03-13
Enrollment: 19
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Part 1: The Rate of Expert-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168)
timeFrame: 24 weeks
measure: Part 2: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE
timeFrame: Part 1: 24 weeks (Week 0 to 24 to 52), Part 2: 28 weeks (Week 24 to 52)
measure: 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.
timeFrame: Part 3: Week 52 to up to Week 104.
Secondary outcomes:
measure: Part 1: Proportion of Days With Angioedema Symptoms Through 24 Weeks.
timeFrame: 24 weeks
measure: Part 1: Rate of Expert-confirmed Angioedema Events During Dosing in the Effective Treatment Period
timeFrame: Day 8 through to 24 weeks
measure: Part 1: Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire at Week 24 (Total Score)
timeFrame: Baseline and 24 weeks
measure: Part 2: To Assess the Effectiveness of Berotralstat Over a 24- to 52-week Period
timeFrame: 28 weeks (Week 24 to 52)
measure: Part 2: To Evaluate QoL Following Berotralstat Administration Over a 24- to 52-week Period.
timeFrame: 28 Weeks (Week 24 to 52)
measure: Part 3: To Assess the Effectiveness of Berotralstat Over a 52- to up to 104-week Administration Period
timeFrame: 52 weeks (Week 52 to 104)
measure: Part 3: To Evaluate QoL Following Berotralstat Administration Over a 52- to up to 104-week Period
timeFrame: 52 Weeks (Week 52 to 104)
measure: Part 3: To Evaluate Subject's Satisfaction With Berotralstat During 52- to 104-week Administration Period
timeFrame: 52 Weeks (Week 52 to 104)
Other outcomes:
Locations:
city: Chiba
country: Japan
facility: Study Site
city: Gunma
country: Japan
facility: Study Site
city: Hokkaido
country: Japan
facility: Study Site
city: Nagoya
country: Japan
facility: Study Site
city: Osaka
country: Japan
facility: Study Site
city: Saga
country: Japan
facility: Study Center
city: Saitama
country: Japan
facility: Study Site
city: Shimane
country: Japan
facility: Study Site
city: Shizuoka
country: Japan
facility: Study Site
city: Tokyo
country: Japan
facility: Study Site
Study officials:
affiliation: Saiyu Soka Hospital
name: Isao Ohsawa
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.