Study of BCX7353 as a Treatment for Attacks of Hereditary Angioedema

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hereditary Angioedema (HAE)

Intervention / Treatment
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* Drug: BCX7353
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAE, hereditary angioedema, kallikrein inhibitor, plasma kallikrein