Clinical trial NCT03485911: Efficacy and Safety Study of BCX7353 as an Oral Treatment for the Prevention of Attacks in HAE
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
Berotralstat
Lead sponsor: BioCryst Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-04-03
Enrollment: 121
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, 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.


Eligibility 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

Primary outcomes:
measure: Part 1: The Rate of Investigator-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168)
timeFrame: 24 weeks
measure: Part 2 & 3: To Evaluate the Long-term Safety and Tolerability of Berotralstat 110 and 150 mg in Subjects With HAE
timeFrame: Part 2: 24 weeks (Days 169 to 337). Part 3: 48 weeks (Days 338 to 674).
Secondary outcomes:
measure: Part 1: Change From Baseline in Angioedema Quality of Life Questionnaire at Week 24 (Total Score)
timeFrame: Baseline and 24 weeks
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 (or or the last dose date/time in Part 1 + 24 hours for subjects who discontinued drug in Part 1)
measure: Part 2: To Assess the Effectiveness of Berotralstat Over a 24- to 48 Week Period
timeFrame: 24 weeks (Days 169 to 337)
measure: To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks
timeFrame: Up to 144 weeks
measure: To Evaluate Treatment Satisfaction Questionnaire for Medication (TSQM) Following Berotralstat Administration for up to 144 Weeks
timeFrame: Up to 144 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Study center
state: Alabama
city: Scottsdale
country: United States
facility: Study center
state: Arizona
city: Little Rock
country: United States
facility: Study center
state: Arkansas
city: San Diego
country: United States
facility: Study Center
state: California
city: Santa Monica
country: United States
facility: Study center
state: California
city: Walnut Creek
country: United States
facility: Study Center
state: California
city: Colorado Springs
country: United States
facility: Study center
state: Colorado
city: Tampa
country: United States
facility: Study Center
state: Florida
city: Chevy Chase
country: United States
facility: Study center
state: Maryland
city: Boston
country: United States
facility: Study Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Study Center
state: Michigan
city: Plymouth
country: United States
facility: Study center
state: Minnesota
city: Saint Louis
country: United States
facility: Study Center
state: Missouri
city: Belleville
country: United States
facility: Study center
state: New Jersey
city: Fair Lawn
country: United States
facility: Study Center
state: New Jersey
city: Piscataway
country: United States
facility: Study center
state: New Jersey
city: New York
country: United States
facility: Study Center
state: New York
city: Charlotte
country: United States
facility: Study Site
state: North Carolina
city: Durham
country: United States
facility: Study Center
state: North Carolina
city: Cincinnati
country: United States
facility: Study Center
state: Ohio
city: Columbus
country: United States
facility: Study center
state: Ohio
city: Clackamas
country: United States
facility: Study center
state: Oregon
city: Hershey
country: United States
facility: Study Center
state: Pennsylvania
city: Austin
country: United States
facility: Study center
state: Texas
city: Dallas
country: United States
facility: Study center
state: Texas
city: San Antonio
country: United States
facility: Study Center
state: Texas
city: Spokane
country: United States
facility: Study Center
state: Washington
city: Vienna
country: Austria
facility: Study Center
city: Ottawa
country: Canada
facility: Study Center
state: Ontario
city: Toronto
country: Canada
facility: Study Center
state: Ontario
city: Québec
country: Canada
facility: Study Center
city: Brno
country: Czechia
facility: Study Center
city: Plzen
country: Czechia
facility: Study Center
city: Grenoble
country: France
facility: Study Center
city: Paris
country: France
facility: Study Center
city: Berlin
country: Germany
facility: Study Center
city: Frankfurt
country: Germany
facility: Study Center
city: Budapest
country: Hungary
facility: Study Center
city: Skopje
country: North Macedonia
facility: Study Center
city: Sângeorgiu de Mureș
country: Romania
facility: Study Center
state: Jud. Mureș
city: Barcelona
country: Spain
facility: Study Center
city: Madrid
country: Spain
facility: Study Center
city: Seville
country: Spain
facility: Study Center
city: Cambridge
country: United Kingdom
facility: Study Center
city: Frimley
country: United Kingdom
facility: Study Center
city: London
country: United Kingdom
facility: Study Center
city: Plymouth
country: United Kingdom
facility: Study Center
Study officials:
affiliation: UC San Diego School of Medicine, US HAE Angioedema Center
name: Bruce Zuraw, MD
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: Wedner HJ, Aygoren-Pursun E, Bernstein J, Craig T, Gower R, Jacobs JS, Johnston DT, Lumry WR, Zuraw BL, Best JM, Iocca HA, Murray SC, Desai B, Nagy E, Sheridan WP, Kiani-Alikhan S. Randomized Trial of the Efficacy and Safety of Berotralstat (BCX7353) as an Oral Prophylactic Therapy for Hereditary Angioedema: Results of APeX-2 Through 48 Weeks (Part 2). J Allergy Clin Immunol Pract. 2021 Jun;9(6):2305-2314.e4. doi: 10.1016/j.jaip.2021.03.057. Epub 2021 Apr 15.
citation: Zuraw B, Lumry WR, Johnston DT, Aygoren-Pursun E, Banerji A, Bernstein JA, Christiansen SC, Jacobs JS, Sitz KV, Gower RG, Gagnon R, Wedner HJ, Kinaciyan T, Hakl R, Hanzlikova J, Anderson JT, McNeil DL, Fritz SB, Yang WH, Tachdjian R, Busse PJ, Craig TJ, Li HH, Farkas H, Best JM, Clemons D, Cornpropst M, Dobo SM, Iocca HA, Kargl D, Nagy E, Murray SC, Collis P, Sheridan WP, Maurer M, Riedl MA. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial. J Allergy Clin Immunol. 2021 Jul;148(1):164-172.e9. doi: 10.1016/j.jaci.2020.10.015. Epub 2020 Oct 21.