Study of BCX7353 as a Treatment for Attacks of Hereditary Angioedema

A Randomized, Double-blind, Placebo-controlled, Dose-ranging, Study to Evaluate the Efficacy, Safety and Tolerability of Single Doses of BCX7353 as an Acute Attack Treatment in Subjects With Hereditary Angioedema

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.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema (HAE)
• Intervention / Treatment: Drug: BCX7353; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • Study Center
• Denmark
  • Odense, Denmark
    • Study Center
• France
  • Grenoble, France
    • Study Center
  • Lille, France
    • Study Center
• Germany
  • Berlin, Germany
    • Study Center
  • Frankfurt, Germany
    • Study Center
• Hungary
  • Budapest, Hungary
    • Study Center
• Israel
  • Ashkelon, Israel
    • Study Center
  • Tel Aviv, Israel
    • Study Center
  • Tel HaShomer, Israel
    • Study Center
• Italy
  • Milano, Italy
    • Study Center
  • Padova, Italy
    • Study Center
  • Salerno, Italy
    • Study Center
• North Macedonia
  • Skopje, North Macedonia
    • Study Center
• Poland
  • Kraków, Poland
    • Study Center
• Romania
  • Târgu-Mureş, Romania
    • Study Center
• Switzerland
  • Zürich, Switzerland
    • Study Center
• United Kingdom
  • Birmingham, United Kingdom
    • Study Center
  • Bristol, United Kingdom
    • Study Center
  • Cambridge, United Kingdom
    • Study Center
  • London, United Kingdom
    • Study Center
  • Manchester, United Kingdom
    • Study Center
  • Plymouth, United Kingdom
    • Study Center
  • Southampton, United Kingdom
    • Study Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able to provide written, informed consent.
2. 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.
3. Access to and ability to use standard of care acute attack treatment for attacks of HAE.
4. Sexually active women of child-bearing potential and sexually active men must utilize effective contraception.

Exclusion Criteria:

1. Women who are pregnant or breast-feeding.
2. Any clinical condition or medical history that would interfere with the subject's safety or ability to participate in the study.
3. Use of C1INH, androgens or tranexamic acid for prophylaxis of HAE attacks.
4. History of or current alcohol or drug abuse.
5. Infection with hepatitis B, hepatitis C or HIV.
6. Participation in any other investigational drug study currently or within the last 30 days.
7. Positive drugs of abuse screen (unless as used as medical treatment, e.g., with a prescription).
8. An immediate family relationship to either Sponsor employees, the Investigator or employees of the study site.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part1: BCX7353 750 mg	Drug: BCX7353; oral liquid formulation
Experimental: Part 2: BCX7353 500 mg	Drug: BCX7353; oral liquid formulation
Experimental: Part 3: BCX7353 250 mg	Drug: BCX7353; oral liquid formulation
Placebo Comparator: Parts 1, 2 and 3: placebo	Drug: Placebo; oral liquid formulation to match BCX7353

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals
• Investigators: Principal Investigator: Hilary Longhurst, MBBS, PhD, Barts & The London NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2017
• Primary Completion (Actual): January 29, 2019
• Study Completion (Actual): January 29, 2019

Study Registration Dates

• First Submitted: August 2, 2017
• First Submitted That Met QC Criteria: August 3, 2017
• First Posted (Actual): August 4, 2017

Study Record Updates

• Last Update Posted (Actual): April 1, 2021
• Last Update Submitted That Met QC Criteria: March 8, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: HAE; hereditary angioedema; kallikrein inhibitor; plasma kallikrein
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Berotralstat
• Other Study ID Numbers: BCX7353-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No