NCT02870972

Brief Summary

This 3-part study will evaluate the safety and efficacy of an oral treatment, BCX7353, in preventing angioedema attacks in subjects with hereditary angioedema (HAE). In Part 1 of the study, eligible subjects will be randomized to receive oral BCX7353 or placebo for 4 weeks. Assuming successful completion of Part 1, additional subjects will be randomized in Part 2 to one of 2 lower doses of BCX7353 or placebo. Part 3 will enroll additional subjects into one of three doses of BCX7353 or placebo. The study will compare the number of acute attacks in each treatment group, as well as a number of other clinical and pharmacologic outcomes, and the safety and tolerability of each dose of BCX7353 compared to placebo.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
75

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Aug 2016

Shorter than P25 for phase_2

Geographic Reach
10 countries

22 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2016

Completed
9 days until next milestone

First Submitted

Initial submission to the registry

August 10, 2016

Completed
8 days until next milestone

First Posted

Study publicly available on registry

August 18, 2016

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2017

Completed
3.6 years until next milestone

Results Posted

Study results publicly available

March 4, 2021

Completed
Last Updated

March 23, 2021

Status Verified

March 1, 2021

Enrollment Period

1 year

First QC Date

August 10, 2016

Results QC Date

November 17, 2020

Last Update Submit

March 3, 2021

Conditions

Outcome Measures

Primary Outcomes (2)

  • Number of Confirmed HAE Attacks

    Efficacy was evaluated by the number of acute angioedema attacks. To ensure that consistent, objective assessments were used in accepting subject-reported attack data, a panel of expert physicians in the treatment of HAE patients adjudicated all subject-reported attacks prior to their inclusion in primary efficacy analyses.

    Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).

  • Proportion of Subjects Who Were HAE Attack-free During the Entire Dosing Period

    Assessment of the proportion of subjects who had no HAE attacks during the entire dosing period

    Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).

Secondary Outcomes (6)

  • Number of Confirmed Abdominal HAE Attacks

    Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).

  • Number of Confirmed Peripheral HAE Attacks

    Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).

  • HAE Attacks Requiring Treatment

    Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).

  • HAE Disease Activity - Modified Angioedema Activity Score

    28-day treatment period + 1 day

  • Angioedema Quality of Life (AE-QoL)

    The subject-completed AE-QoL was administered at baseline (Day 1) and at Day 29

  • +1 more secondary outcomes

Study Arms (5)

Part 1: BCX7353 350 mg once daily

EXPERIMENTAL

BCX7353 capsules, 350 mg dose administered once per day for 28 days

Drug: BCX7353

Parts 2 and 3: BCX7353 250 mg once daily

EXPERIMENTAL

BCX7353 capsules, 250 mg dose administered once per day for 28 days

Drug: BCX7353

Parts 2 and 3: BCX7353 125 mg once daily

EXPERIMENTAL

BCX7353 capsules, 125 mg dose administered once per day for 28 days

Drug: BCX7353

Parts 1, 2 and 3: Placebo

PLACEBO COMPARATOR

Placebo capsules, administered once per day for 28 days

Drug: Placebo

Part 3: BCX7353 62.5 mg once daily

EXPERIMENTAL

BCX7353 capsules, 62.5 mg dose administered once per day for 28 days

Drug: BCX7353

Interventions

Plasma kallikrein inhibitor

Part 1: BCX7353 350 mg once dailyPart 3: BCX7353 62.5 mg once dailyParts 2 and 3: BCX7353 125 mg once dailyParts 2 and 3: BCX7353 250 mg once daily
Parts 1, 2 and 3: Placebo

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • A clinical diagnosis of HAE type I or II
  • Documented HAE attacks within a defined calendar period
  • Access to acute attack medications
  • Sexually active women of child-bearing potential and sexually active men must utilize effective contraception

You may not qualify if:

  • Women who are pregnant or breast-feeding
  • Any clinical condition or medical history that would interfere with the subject's safety or ability to participate in the study
  • Use of C1INH, androgens or tranexamic acid for prophylaxis of HAE attacks
  • History of or current alcohol or drug abuse
  • Infection with hepatitis B, hepatitis C or HIV
  • Participation in any other investigational drug study currently or within the last 30 days

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

Unknown Facility

Adelaide, Australia

Location

Unknown Facility

Campbelltown, Australia

Location

Unknown Facility

Graz, Austria

Location

Unknown Facility

Vienna, Austria

Location

Unknown Facility

Québec, Canada

Location

Unknown Facility

Toronto, Canada

Location

Unknown Facility

Odense, Denmark

Location

Unknown Facility

Berlin, Germany

Location

Unknown Facility

Frankfurt, Germany

Location

Unknown Facility

Ulm, Germany

Location

Unknown Facility

Budapest, Hungary

Location

Unknown Facility

Milan, Italy

Location

Unknown Facility

Padua, Italy

Location

Unknown Facility

Salerno, Italy

Location

Unknown Facility

Skopje, North Macedonia

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Seville, Spain

Location

Unknown Facility

Zurich, Switzerland

Location

Unknown Facility

Brimingham, United Kingdom

Location

Unknown Facility

Bristol, United Kingdom

Location

Unknown Facility

London, United Kingdom

Location

Unknown Facility

Oxford, United Kingdom

Location

Unknown Facility

Southampton, United Kingdom

Location

Related Publications (3)

  • 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.

  • 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.

  • Aygoren-Pursun E, Bygum A, Grivcheva-Panovska V, Magerl M, Graff J, Steiner UC, Fain O, Huissoon A, Kinaciyan T, Farkas H, Lleonart R, Longhurst HJ, Rae W, Triggiani M, Aberer W, Cancian M, Zanichelli A, Smith WB, Baeza ML, Du-Thanh A, Gompels M, Gonzalez-Quevedo T, Greve J, Guilarte M, Katelaris C, Dobo S, Cornpropst M, Clemons D, Fang L, Collis P, Sheridan W, Maurer M, Cicardi M. Oral Plasma Kallikrein Inhibitor for Prophylaxis in Hereditary Angioedema. N Engl J Med. 2018 Jul 26;379(4):352-362. doi: 10.1056/NEJMoa1716995.

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

berotralstat

Condition Hierarchy (Ancestors)

AngioedemaVascular DiseasesCardiovascular DiseasesHereditary Complement Deficiency DiseasesPrimary Immunodeficiency DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesUrticariaSkin Diseases, VascularSkin DiseasesSkin and Connective Tissue DiseasesHypersensitivity, ImmediateHypersensitivityImmune System DiseasesImmunologic Deficiency Syndromes

Results Point of Contact

Title
Study Director
Organization
BioCryst Pharmaceuticals Inc

Study Officials

  • Emel Aygören-Pürsün, MD

    University Hospital Frankfurt Goethe University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 10, 2016

First Posted

August 18, 2016

Study Start

August 1, 2016

Primary Completion

August 1, 2017

Study Completion

August 1, 2017

Last Updated

March 23, 2021

Results First Posted

March 4, 2021

Record last verified: 2021-03

Data Sharing

IPD Sharing
Will share

Locations