Hereditary AngioedemaPhase 2/3OPuS-2NCT02303626
12-Week Safety and Efficacy Study of BCX4161 as an Oral Prophylaxis Against HAE Attacks
A Phase 2/3 study testing BCX4161 in people with Hereditary Angioedema and HAE, run by BioCryst Pharmaceuticals at 40 sites in 8 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Angioedema, HAE
- What is being tested?
- BCX4161
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- 40 sitesin 8 countries
- Study dates
- 17 Dec 2014to Jan 2016
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A clinical diagnosis of HAE type I or II
- 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
- Access to acute attack medications
- Sexually active women of child-bearing potential and sexually active men must utilize highly effective contraception
Who cannot join
- 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 or tranexamic acid for prophylaxis of HAE attacks
- Current participation in any other investigational drug study or within the last 30 days
- History of or current alcohol or drug abuse
- Infection with hepatitis B, hepatitis C or HIV
Trial locations and contacts
40 sites in 8 countries.
40 sites in 8 countries
United States25 sites
Study site
Birmingham, Alabama, 35209
Study site
Boston, Massachusetts, 02114
Study site
Charlotte, North Carolina, 28277
Study site
Chevy Chase, Maryland, 20815
Study site
Cincinnati, Ohio, 45267
Study site
Colorado Springs, Colorado, 80907
Study site
Dallas, Texas, 75231
Study site
Fairfax, Virginia, 63141
Study site
Galveston, Texas, 77555
Study site
Granada Hills, California, 91344
Study site
Hershey, Pennsylvania, 17033
Study site
Lake Oswego, Oregon, 97035
Study site
New York, New York, 10029
Study site
Oklahoma City, Oklahoma, 73131
Study site
Pittsburgh, Pennsylvania, 15241
Study site
Plymouth, Minnesota, 55446
Study site
San Diego, California, 92093
Study site
San Diego, California, 92112
Study site
Scottsdale, Arizona, 85251
Study site
Shreveport, Louisiana, 71106
Study site
Spokane, Washington, 99204
Study site
St Louis, Missouri, 63141
Study site
Tacoma, Washington, 98405
Study site
Tulsa, Oklahoma, 74133
Study site
Walnut Creek, California, 94598
United Kingdom5 sites
Study site
Birmingham
Study site
Bristol
Study site
Cardiff
Study site
London
Study site
Manchester
Germany3 sites
Study site
Berlin
Study site
Frankfurt
Study site
Mörfelden-Walldorf
About this study
Official title: 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.
- Conditions
- Hereditary Angioedema, HAE
- Being tested
- BCX4161, Placebo
- Keywords
- BCX4161, Prophylaxis, Prevention, HAE, Hereditary Angioedema
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCX4161Drug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| BCX4161 300 mg three times daily | Experimental | Three BCX4161 capsules (100 mg) and two placebo capsules to be taken three times daily by mouth Receives: Drug: BCX4161; Drug: Placebo |
| BCX4161 500 mg three times daily | Experimental | Five BCX4161 capsules (100 mg) to be taken three times daily by mouth Receives: Drug: BCX4161 |
| Placebo three times daily | Placebo comparator | Five placebo capsules to be taken three times daily by mouth Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (6)
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.
Measured: 12 weeks
Number of Participants Who Are Attack-free
The number of participants who reported no attacks during the 12-week treatment period.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: Baseline (Day 1) and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2014 (estimated)
- Study start17 Dec 2014
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioCryst Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marc Riedl, MD MS, Principal investigator, UCSD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02303626
- Sponsor's protocol ID
- BCX4161-301
- Acronym
- OPuS-2
- Status last verified
- Nov 2025
- First submitted
- 24 Nov 2014
- Last updated
- 17 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 36326435
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02303626
- Acronym / sponsor ID
- OPuS-2 / BCX4161-301
- Conditions
- Hereditary Angioedema, HAE
- Keywords
- BCX4161, Prophylaxis, Prevention, HAE, Hereditary Angioedema
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- BioCryst PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 17 Dec 2014 (actual)
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 1 Dec 2014 (estimated)
- Results
- Posted 17 Nov 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BCX4161 300 mg three times daily | Experimental | Drug: BCX4161, Drug: PlaceboThree BCX4161 capsules (100 mg) and two placebo capsules to be taken three times daily by mouth |
| BCX4161 500 mg three times daily | Experimental | Drug: BCX4161Five BCX4161 capsules (100 mg) to be taken three times daily by mouth |
| Placebo three times daily | Placebo comparator | Drug: PlaceboFive placebo capsules to be taken three times daily by mouth |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- A clinical diagnosis of HAE type I or II
- 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
- Access to acute attack medications
- Sexually active women of child-bearing potential and sexually active men must utilize highly effective contraception
Key exclusion criteria (6 listed)
- 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 or tranexamic acid for prophylaxis of HAE attacks
- Current participation in any other investigational drug study or within the last 30 days
- History of or current alcohol or drug abuse
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCX4161 | Drug | BCX4161 300 mg three times daily, BCX4161 500 mg three times daily |
| Placebo | Drug | BCX4161 300 mg three times daily, Placebo three times daily |
Primary outcome
The Mean Acute Angioedema Attack Rate
Time frame: 12 weeks
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.
6 secondary outcomes
Number of Attack-free Days
Time frame: 12 weeks
Number of Participants Who Are Attack-free
Time frame: 12 weeks
Disease Activity, as Measured by the 84-day Angioedema Activity Score
Time frame: 12 weeks
Change From Baseline at Week 12, in Quality of Life as Measured by the Angioedema Quality of Life Questionnaire
Time frame: Baseline (Day 1) and Week 12
Number of Participants With Treatment Emergent Adverse Events
Time frame: 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
Time frame: Baseline (Day 1) and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36326435Beard 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Riedl, MD MS principal investigator
UCSD
40 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing BCX4161 in people with Hereditary Angioedema and HAE, run by BioCryst Pharmaceuticals at 40 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States, United Kingdom, France, Germany, Belgium and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Mean Acute Angioedema Attack Rate (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02303626, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2025.