Study of BCX7353 as a Treatment for Attacks of Hereditary Angioedema
Primary Purpose
Hereditary Angioedema (HAE)
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BCX7353
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hereditary Angioedema (HAE) focused on measuring HAE, hereditary angioedema, kallikrein inhibitor, plasma kallikrein
Eligibility Criteria
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.
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Part1: BCX7353 750 mg
Part 2: BCX7353 500 mg
Part 3: BCX7353 250 mg
Parts 1, 2 and 3: placebo
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03240133
Brief Title
Study of BCX7353 as a Treatment for Attacks of Hereditary Angioedema
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
July 31, 2017 (Actual)
Primary Completion Date
January 29, 2019 (Actual)
Study Completion Date
January 29, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioCryst Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema (HAE)
Keywords
HAE, hereditary angioedema, kallikrein inhibitor, plasma kallikrein
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part1: BCX7353 750 mg
Arm Type
Experimental
Arm Title
Part 2: BCX7353 500 mg
Arm Type
Experimental
Arm Title
Part 3: BCX7353 250 mg
Arm Type
Experimental
Arm Title
Parts 1, 2 and 3: placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
BCX7353
Intervention Description
oral liquid formulation
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
oral liquid formulation to match BCX7353
Primary Outcome Measure Information:
Title
Proportion of Subjects With Improved or Stable Composite Visual Analog Scale (VAS) Score
Description
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.
Time Frame
Mean composite VAS for HAE attack symptoms severity prior to IMP treatment and 4 hours post-dose
Title
Percentage of Attacks Treated With Standard of Care Acute Attack Medication (SOC-Rx) Through 24 Hours
Description
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.
Time Frame
24 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hilary Longhurst, MBBS, PhD
Organizational Affiliation
Barts & The London NHS Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Study Center
City
Graz
Country
Austria
Facility Name
Study Center
City
Odense
Country
Denmark
Facility Name
Study Center
City
Grenoble
Country
France
Facility Name
Study Center
City
Lille
Country
France
Facility Name
Study Center
City
Berlin
Country
Germany
Facility Name
Study Center
City
Frankfurt
Country
Germany
Facility Name
Study Center
City
Budapest
Country
Hungary
Facility Name
Study Center
City
Ashkelon
Country
Israel
Facility Name
Study Center
City
Tel Aviv
Country
Israel
Facility Name
Study Center
City
Tel HaShomer
Country
Israel
Facility Name
Study Center
City
Milano
Country
Italy
Facility Name
Study center
City
Padova
Country
Italy
Facility Name
Study Center
City
Salerno
Country
Italy
Facility Name
Study Center
City
Skopje
Country
North Macedonia
Facility Name
Study Center
City
Kraków
Country
Poland
Facility Name
Study Center
City
Târgu-Mureş
Country
Romania
Facility Name
Study Center
City
Zürich
Country
Switzerland
Facility Name
Study Center
City
Birmingham
Country
United Kingdom
Facility Name
Study Center
City
Bristol
Country
United Kingdom
Facility Name
Study Center
City
Cambridge
Country
United Kingdom
Facility Name
Study Center
City
London
Country
United Kingdom
Facility Name
Study Center
City
Manchester
Country
United Kingdom
Facility Name
Study Center
City
Plymouth
Country
United Kingdom
Facility Name
Study Center
City
Southampton
Country
United Kingdom
12. IPD Sharing Statement
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Study of BCX7353 as a Treatment for Attacks of Hereditary Angioedema
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