12-Week Safety and Efficacy Study of BCX4161 as an Oral Prophylaxis Against HAE Attacks (OPuS-2)

OPuS-2: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Two Dose Levels of BCX4161 for 12 Weeks as an Oral Prophylaxis Treatment for Attacks of Hereditary Angioedema

This study will evaluate the safety and efficacy of an oral treatment, BCX4161, in preventing acute attacks in participants with hereditary angioedema (HAE). Eligible participants will be randomized to receive one of two doses of BCX4161 or placebo for 12 weeks. The study will compare the number of acute attacks in each treatment group, as well as a number of other clinical outcomes, and the safety and tolerability of each dose of BCX4161 compared to placebo.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema; HAE
• Intervention / Treatment: Drug: Placebo; Drug: BCX4161

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
• Canada
  • Ottawa, Canada
• France
  • Grenoble, France
  • Lille, France
  • Paris, France
• Germany
  • Berlin, Germany
  • Frankfurt, Germany
  • Mörfelden-Walldorf, Germany
• Hungary
  • Budapest, Hungary
• Italy
  • Milan, Italy
• United Kingdom
  • Birmingham, United Kingdom
  • Bristol, United Kingdom
  • Cardiff, United Kingdom
  • London, United Kingdom
  • Manchester, United Kingdom
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
  • Arizona
    • Scottsdale, Arizona, United States, 85251
  • California
    • Granada Hills, California, United States, 91344
    • San Diego, California, United States, 92093
    • San Diego, California, United States, 92112
    • Walnut Creek, California, United States, 94598
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
  • Louisiana
    • Shreveport, Louisiana, United States, 71106
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
  • Missouri
    • St Louis, Missouri, United States, 63141
  • New York
    • New York, New York, United States, 10029
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
  • Ohio
    • Cincinnati, Ohio, United States, 45267
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73131
    • Tulsa, Oklahoma, United States, 74133
  • Oregon
    • Lake Oswego, Oregon, United States, 97035
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
    • Pittsburgh, Pennsylvania, United States, 15241
  • Texas
    • Dallas, Texas, United States, 75231
    • Galveston, Texas, United States, 77555
  • Virginia
    • Fairfax, Virginia, United States, 63141
  • Washington
    • Spokane, Washington, United States, 99204
    • Tacoma, Washington, United States, 98405

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. A clinical diagnosis of HAE type I or II
2. Documented HAE attacks within a defined calendar period; in the absence of documented HAE attacks, participants will be required to enter a run-in period to document attacks
3. Access to acute attack medications
4. Sexually active women of child-bearing potential and sexually active men must utilize highly effective contraception

Key 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 or tranexamic acid for prophylaxis of HAE attacks
4. Current participation in any other investigational drug study or within the last 30 days
5. History of or current alcohol or drug abuse
6. Infection with hepatitis B, hepatitis C or HIV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCX4161 300 mg three times daily; Three BCX4161 capsules (100 mg) and two placebo capsules to be taken three times daily by mouth	Drug: Placebo; Drug: BCX4161
Experimental: BCX4161 500 mg three times daily; Five BCX4161 capsules (100 mg) to be taken three times daily by mouth	Drug: BCX4161
Placebo Comparator: Placebo three times daily; Five placebo capsules to be taken three times daily by mouth	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Mean Acute Angioedema Attack Rate	An angioedema attack was defined as swelling at any location reported by participant, which had no swelling earlier. Total number of confirmed attacks during the treatment period standardized to a weekly attack-rate to adjust for the total duration of treatment. The attack rate was derived for each participant by treatment period. The weekly attack rate was equal to the total number of confirmed attacks during a treatment period divided by the duration of the treatment (in days) times 7 days.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Attack-free Days	The number of attack free days was the sum of the days during the treatment period for which participants reported no attacks.	12 weeks
Number of Participants Who Are Attack-free	The number of participants who reported no attacks during the 12-week treatment period.	12 weeks
Disease Activity, as Measured by the 84-day Angioedema Activity Score	Angioedema Activity Score (AAS) consists of 5 questions (period in which swelling occurred, physical discomfort, daily activity restriction, cosmetic disfigurement, and overall severity) to be answered for each day during which a subject experiences an HAE attack. A score between 0 (no symptoms) and 3 (Severe symptoms) was assigned to the responses for each question and the total daily score will be derived as the sum of the 5 question scores for each day during which the subject experiences a confirmed attack. Daily AAS ranged from 0 to 15 with higher scores indicating the greater disease severity. For participants who completed the study, the 84-day AAS was obtained by sum of AAS score during the treatment period and ranged from 0 (best) to 1,260 (worst).For participants who discontinued the study prematurely the 84-day AAS was obtained using the formula: Sum of AAS score of each day on treatment ∗ 84/Number of days on treatment.	12 weeks
Change From Baseline at Week 12, in Quality of Life as Measured by the Angioedema Quality of Life Questionnaire	Angioedema Quality of Life questionnaire (AE-QoL) consisted of 4 domains (i.e., functioning, fatigue/mood, fear/shame, and nutrition) and a total score based on a total of 17 possible responses. The results of all the responses are summed up and transformed to a scale ranging from 0 (best) to 100 (worst).	Baseline (Day 1) and Week 12
Number of Participants With Treatment Emergent Adverse Events	An adverse event (AE) is any untoward medical occurrence in a clinical study participant. No causal relationship with study drug or with the clinical study itself is implied. An AE could be an unfavorable and unintended sign, symptom (including an abnormal laboratory finding), syndrome, or illness that developed or worsened during the clinical study. A serious adverse event (SAE) is any untoward medical occurrence resulting in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or other medically important event. Any graded abnormality that occurred following the initiation of study drug and up to 30 days after the last dose of study drug, and represented at least a 1-grade increase from the baseline assessment, was defined as treatment emergent.	From first dose up to 14 weeks
Change From Baseline at Week 12 in Quality of Life, as Measured by the EuroQoL Five-dimensional, 5-level Questionnaire	The EuroQoL five-dimensional, 5-level (EQ-5D-5L) was used to assess overall wellbeing and comprised the following five domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each domain has 5 response levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. It included the EQ Visual Analogue scale (EQ VAS) to rate overall health on a scale of 0 (worst health) to 100 (best health).	Baseline (Day 1) and Week 12

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals
• Investigators: Principal Investigator: Marc Riedl, MD MS, UCSD

Publications and helpful links

General Publications

• Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: November 24, 2014
• First Submitted That Met QC Criteria: November 25, 2014
• First Posted (Estimated): December 1, 2014

Study Record Updates

• Last Update Posted (Estimated): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 3, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Prevention; Prophylaxis; HAE; Hereditary Angioedema; BCX4161
• Additional Relevant MeSH Terms: Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immunologic Deficiency Syndromes; Skin Diseases; Urticaria; Skin Diseases, Vascular; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Angioedema; Angioedemas, Hereditary; avoralstat
• Other Study ID Numbers: BCX4161-301