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

NCT03485911 | Completed Phase 3 Results FDA Drug

• 1 other identifier: BCX7353-302
• Study Type: interventional
• Target: 121
• Locations: 11 countries
• Sites: 47

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.

Conditions

Hereditary Angioedema; HAE

Keywords

BCX7353; Berotralstat

Outcome Measures

Primary Outcomes (2)

• Part 1: The Rate of Investigator-confirmed HAE Attacks During Dosing in the Entire 24-week Treatment Period (Day 1 to Day 168)

  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.

  24 weeks

• Part 2 & 3: 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 Part 3, and includes TEAEs that began in Part 2 or 3, respectively, for these subjects. Safety data for Part 2 and Part 3 is combined to clearly show TEAEs occurring in subjects as the proceeded through the 2 study parts. 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 2 or Part 3 treatment). No statistical analysis was performed on this safety data.

  Part 2: 24 weeks (Days 169 to 337). Part 3: 48 weeks (Days 338 to 674).

Secondary Outcomes (6)

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

  Baseline and 24 weeks

• 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 (or or the last dose date/time in Part 1 + 24 hours for subjects who discontinued drug in Part 1)

• Part 2: To Assess the Effectiveness of Berotralstat Over a 24- to 48 Week Period

  24 weeks (Days 169 to 337)

• To Evaluate Angioedema Quality of Life Questionnaire (Total Score) Following Berotralstat Administration for up to 144 Weeks

  Up to 144 weeks

Study Arms (3)

BCX7353 110 mg once daily

EXPERIMENTAL

BCX7353 administered as oral capsules once daily

Drug: BCX7353 capsules

BCX7353 150 mg once daily

EXPERIMENTAL

BCX7353 administered as oral capsules once daily

Drug: BCX7353 capsules

Placebo

PLACEBO COMPARATOR

Matching placebo administered as oral capsules once daily

Drug: Placebo oral capsule

Interventions

BCX7353 capsules DRUG

BCX7353 oral capsules administered once daily

Also known as: Berotralstat

BCX7353 110 mg once daily; BCX7353 150 mg once daily

Placebo oral capsule DRUG

Matching oral capsules administered once daily

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

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 (47)

Study center

Birmingham, Alabama, 35209, United States

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Scottsdale, Arizona, 85251, United States

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Little Rock, Arkansas, 72205, United States

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San Diego, California, 92122, United States

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Santa Monica, California, 90404, United States

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Walnut Creek, California, 94598, United States

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Colorado Springs, Colorado, 80907, United States

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Tampa, Florida, 33613, United States

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Chevy Chase, Maryland, 20815, United States

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Boston, Massachusetts, 02114, United States

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Ann Arbor, Michigan, 48106, United States

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Plymouth, Minnesota, 55446, United States

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St Louis, Missouri, 63141, United States

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Belleville, New Jersey, 07109, United States

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Fair Lawn, New Jersey, 07410, United States

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Piscataway, New Jersey, 08854, United States

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New York, New York, 10029, United States

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Charlotte, North Carolina, 28277, United States

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Durham, North Carolina, 27705, United States

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Cincinnati, Ohio, 45231, United States

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Columbus, Ohio, 43235, United States

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Clackamas, Oregon, 97015, United States

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Hershey, Pennsylvania, 17033, United States

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Austin, Texas, 78731, United States

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Dallas, Texas, 75231, United States

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San Antonio, Texas, 78229, United States

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Spokane, Washington, 99202, United States

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Vienna, 1090, Austria

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Ottawa, Ontario, K1G 6C6, Canada

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Toronto, Ontario, M4V 1R2, Canada

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Québec, G1V 4W2, Canada

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Brno, 656 91, Czechia

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Pilsen, 30460, Czechia

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Grenoble, 38043, France

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Paris, 75012, France

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Berlin, 10117, Germany

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Frankfurt, D-60590, Germany

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Budapest, H-1225, Hungary

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Skopje, 1000, North Macedonia

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Sângeorgiu de Mureș, Jud. Mureș, 547530, Romania

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Barcelona, 08907, Spain

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Madrid, 28046, Spain

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Seville, 41013, Spain

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Cambridge, CB2 0QQ, United Kingdom

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Frimley, GU16 7UJ, United Kingdom

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London, E1 2ES, United Kingdom

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Plymouth, PL6 8DH, United Kingdom

Location

Related Publications (4)

• 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

• 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.

  PMID: 33866032 DERIVED

• 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.

  PMID: 33098856 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

• Bruce Zuraw, MD

  UC San Diego School of Medicine, US HAE Angioedema Center

  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
• Masking Details: Only Part 1 and Part 2 were blinded. As part 3 was open-label, no blinding was used
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2018
• First Posted: April 3, 2018
• Study Start: February 6, 2018
• Primary Completion: April 10, 2019
• Study Completion: April 6, 2022
• Last Updated: June 26, 2023
• Results First Posted: March 2, 2021

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); AU (1); US (27); RO (1); FR (2); GB (4); CZ (2); DE (2); NO (1); ES (3); HU (1)