Study of BCX7353 as a Treatment for Attacks of Hereditary Angioedema

NCT03240133 | Completed Phase 2 Results DMC

• 1 other identifier: BCX7353-202
• Study Type: interventional
• Target: 58
• Locations: 12 countries
• Sites: 24

Brief Summary

This 3-part study will evaluate the efficacy and safety of an oral kallikrein inhibitor, BCX7353, in the treatment angioedema attacks in subjects with Type I or II hereditary angioedema (HAE). In each study part, subjects will treat 3 attacks with BCX7353 (2 attacks) or placebo (1 attack), in a randomly allocated order. In Part 1, the dose of 750mg will be assessed relative to placebo in up to 36 patients. If this is shown to be effective, then a further 12 patients will be enrolled at a 500mg dose (Part 1), followed by a further 12 (if efficacy still shown) at a dose of 250mg (Part 3) to determine the minimum effective dose of BCX7353 compared to placebo for treating HAE attacks. Efficacy will be determined by subject diary entries completed at pre-defined times post-dose.

Conditions

Hereditary Angioedema (HAE)

Keywords

HAE; hereditary angioedema; kallikrein inhibitor; plasma kallikrein

Outcome Measures

Primary Outcomes (2)

• Proportion of Subjects With Improved or Stable Composite Visual Analog Scale (VAS) Score

  Subjects completed a 3-component VAS on a 100 mm scale for severity of abdominal pain, skin pain and skin swelling associated with the HAE attack, where zero indicated no pain or swelling and 100 mm indicated worst possible pain or swelling. Subjects completed the VAS immediately prior to study drug administration, then at 1, 2, 3, 4, approximately 8 \& at 24 hours post-dose. The primary endpoint was the proportion of subject attacks with an improved or stable 3-symptom composite VAS score at 4 hours post dose. The 3-symptom composite was calculated as the average of the VAS scores for abdominal pain, skin pain, and skin swelling. A subject was considered improved or stable if the change from baseline (CFB; time of drug administration) in VAS was ≤ 0.

  Mean composite VAS for HAE attack symptoms severity prior to IMP treatment and 4 hours post-dose

• Percentage of Attacks Treated With Standard of Care Acute Attack Medication (SOC-Rx) Through 24 Hours

  The proportion of attacks for which subjects took SOC-Rx in the 24 hours following treatment with study drug. HAE Rescue Medications included C1-INH (Berinert, Cinryze, Ruconest) and Firazyr/Icatibant.

  24 hours

Study Arms (4)

Part1: BCX7353 750 mg

EXPERIMENTAL

Drug: BCX7353

Part 2: BCX7353 500 mg

EXPERIMENTAL

Drug: BCX7353

Part 3: BCX7353 250 mg

EXPERIMENTAL

Drug: BCX7353

Parts 1, 2 and 3: placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

BCX7353 DRUG

oral liquid formulation

Part 2: BCX7353 500 mg; Part 3: BCX7353 250 mg; Part1: BCX7353 750 mg

Placebo DRUG

oral liquid formulation to match BCX7353

Parts 1, 2 and 3: placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written, informed consent.
• A clinical diagnosis of hereditary angioedema Type 1 or Type 2 as documented at any time in the medical records or at the screening visit.
• Access to and ability to use standard of care acute attack treatment for attacks of HAE.
• 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.
• Positive drugs of abuse screen (unless as used as medical treatment, e.g., with a prescription).
• An immediate family relationship to either Sponsor employees, the Investigator or employees of the study site.

Sponsors & Collaborators

• BioCryst Pharmaceuticals: lead

Study Sites (24)

Study Center

Graz, Austria

Location

Study Center

Odense, Denmark

Location

Study Center

Grenoble, France

Location

Study Center

Lille, France

Location

Study Center

Berlin, Germany

Location

Study Center

Frankfurt, Germany

Location

Study Center

Budapest, Hungary

Location

Study Center

Ashkelon, Israel

Location

Study Center

Tel Aviv, Israel

Location

Study Center

Tel Litwinsky, Israel

Location

Study Center

Milan, Italy

Location

Study center

Padua, Italy

Location

Study Center

Salerno, Italy

Location

Study Center

Skopje, North Macedonia

Location

Study Center

Krakow, Poland

Location

Study Center

Târgu Mureş, Romania

Location

Study Center

Zurich, Switzerland

Location

Study Center

Birmingham, United Kingdom

Location

Study Center

Bristol, United Kingdom

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Study Center

Cambridge, United Kingdom

Location

Study Center

London, United Kingdom

Location

Study Center

Manchester, United Kingdom

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Study Center

Plymouth, United Kingdom

Location

Study Center

Southampton, United Kingdom

Location

Related Publications (1)

• 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

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

Limitations and Caveats

In this interim clinical study report (CSR), the VAS change from pre-dose at 4 hours and the proportion of attacks requiring SOC-Rx through the 24 hour post dose were discussed. Assessment of other efficacy endpoints were to be discussed in a final CSR, but this is no longer planned due to a decision to not proceed further with trials of acute treatment of HAE attacks with berotralstat.

Results Point of Contact

• Title: Study Director
• Organization: BioCryst Pharmaceuticals Inc

clinicaltrials@biocryst.com

+1 919-859-1302

Study Officials

• Hilary Longhurst, MBBS, PhD

  Barts & The London NHS Trust

  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: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 4, 2017
• Study Start: July 31, 2017
• Primary Completion: January 29, 2019
• Study Completion: January 29, 2019
• Last Updated: April 1, 2021
• Results First Posted: April 1, 2021

Record last verified: 2021-03

Locations

FR (2); HU (1); NO (1); GB (7); DK (1); IT (3); DE (2); PL (1); AU (1); CH (1); IL (3); RO (1)