Study of BCX7353 as a Treatment for Attacks of Hereditary Angioedema

• ClinicalTrials.gov Identifier: NCT03240133
• Recruitment Status: Completed
• First Posted: August 4, 2017
• Results First Posted: April 1, 2021
• Last Update Posted: April 1, 2021
• Sponsor: BioCryst Pharmaceuticals
• Information provided by (Responsible Party): BioCryst Pharmaceuticals

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.

Condition or disease	Intervention/treatment	Phase
Hereditary Angioedema (HAE)	Drug: BCX7353; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: July 31, 2017
• Actual Primary Completion Date: January 29, 2019
• Actual Study Completion Date: January 29, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Proportion of Subjects With Improved or Stable Composite Visual Analog Scale (VAS) Score [ Time Frame: Mean composite VAS for HAE attack symptoms severity prior to IMP treatment and 4 hours post-dose ]
   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.
2. Percentage of Attacks Treated With Standard of Care Acute Attack Medication (SOC-Rx) Through 24 Hours [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Austria

Study Center

Graz, Austria

Denmark

Study Center

Odense, Denmark

France

Study Center

Grenoble, France

Study Center

Lille, France

Germany

Study Center

Berlin, Germany

Study Center

Frankfurt, Germany

Hungary

Study Center

Budapest, Hungary

Israel

Study Center

Ashkelon, Israel

Study Center

Tel Aviv, Israel

Study Center

Tel HaShomer, Israel

Italy

Study Center

Milano, Italy

Study center

Padova, Italy

Study Center

Salerno, Italy

North Macedonia

Study Center

Skopje, North Macedonia

Poland

Study Center

Kraków, Poland

Romania

Study Center

Târgu-Mureş, Romania

Switzerland

Study Center

Zürich, Switzerland

United Kingdom

Study Center

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

Sponsors and Collaborators

BioCryst Pharmaceuticals

Investigators

• Principal Investigator: Hilary Longhurst, MBBS, PhD; Barts & The London NHS Trust

  Study Documents (Full-Text)

Documents provided by BioCryst Pharmaceuticals:

Statistical Analysis Plan  [PDF] January 29, 2019

Study Protocol  [PDF] March 16, 2018

More Information

• Responsible Party: BioCryst Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03240133
• Other Study ID Numbers: BCX7353-202
• First Posted: August 4, 2017
• Results First Posted: April 1, 2021
• Last Update Posted: April 1, 2021
• Last Verified: March 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by BioCryst Pharmaceuticals:

HAE; hereditary angioedema; kallikrein inhibitor; plasma kallikrein

Additional relevant MeSH terms:

Angioedema; Angioedemas, Hereditary; Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Berotralstat; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action