Hereditary Angioedema (HAE)Phase 2APeX-1NCT02870972
Efficacy and Safety of BCX7353 to Prevent Angioedema Attacks in Subjects With Hereditary Angioedema
A Phase 2 study testing BCX7353 in people with Hereditary Angioedema (HAE), run by BioCryst Pharmaceuticals at 24 sites in 11 countries.
Trial summary
This 3-part study will evaluate the safety and efficacy of an oral treatment, BCX7353, in preventing angioedema attacks in subjects with hereditary angioedema (HAE). In Part 1 of the study, eligible subjects will be randomized to receive oral BCX7353 or placebo for 4 weeks. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hereditary Angioedema (HAE)
- What is being tested?
- BCX7353
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 24 sitesin 11 countries
- Study dates
- Aug 2016to Aug 2017
- Phase
- Phase 2
- 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 to 70 years
- 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
- Access to acute attack medications
- Sexually active women of child-bearing potential and sexually active men must utilize 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, 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
Trial locations and contacts
24 sites in 11 countries.
24 sites in 11 countries
United Kingdom5 sites
Study site
Brimingham
Study site
Bristol
Study site
London
Study site
Oxford
Study site
Southampton
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Dose-ranging, Parallel-group Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BCX7353 as a Preventative Treatment to Reduce the Frequency of Attacks in Subjects With Hereditary Angioedema
This 3-part study will evaluate the safety and efficacy of an oral treatment, BCX7353, in preventing angioedema attacks in subjects with hereditary angioedema (HAE). In Part 1 of the study, eligible subjects will be randomized to receive oral BCX7353 or placebo for 4 weeks. Assuming successful completion of Part 1, additional subjects will be randomized in Part 2 to one of 2 lower doses of BCX7353 or placebo. Part 3 will enroll additional subjects into one of three doses of BCX7353 or placebo. The study will compare the number of acute attacks in each treatment group, as well as a number of other clinical and pharmacologic outcomes, and the safety and tolerability of each dose of BCX7353 compared to placebo.
- Conditions
- Hereditary Angioedema (HAE)
- Being tested
- BCX7353, Placebo
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCX7353Drug
Plasma kallikrein inhibitor
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Part 1: BCX7353 350 mg once daily | Experimental | BCX7353 capsules, 350 mg dose administered once per day for 28 days Receives: Drug: BCX7353 |
| Parts 2 and 3: BCX7353 250 mg once daily | Experimental | BCX7353 capsules, 250 mg dose administered once per day for 28 days Receives: Drug: BCX7353 |
| Parts 2 and 3: BCX7353 125 mg once daily | Experimental | BCX7353 capsules, 125 mg dose administered once per day for 28 days Receives: Drug: BCX7353 |
| Parts 1, 2 and 3: Placebo | Placebo comparator | Placebo capsules, administered once per day for 28 days Receives: Drug: Placebo |
| Part 3: BCX7353 62.5 mg once daily | Experimental | BCX7353 capsules, 62.5 mg dose administered once per day for 28 days Receives: Drug: BCX7353 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Confirmed HAE Attacks
Efficacy was evaluated by the number of acute angioedema attacks. To ensure that consistent, objective assessments were used in accepting subject-reported attack data, a panel of expert physicians in the treatment of HAE patients adjudicated all subject-reported attacks prior to their inclusion in primary efficacy analyses.
Measured: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).
Proportion of Subjects Who Were HAE Attack-free During the Entire Dosing Period
Assessment of the proportion of subjects who had no HAE attacks during the entire dosing period
Measured: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).
Secondary outcomes (6)
Number of Confirmed Abdominal HAE Attacks
A prespecified secondary endpoint analyzed confirmed attacks by anatomical location; abdominal HAE attacks included any abdominal symptoms (i.e. swelling in the stomach/gut, or any symptoms of nausea, vomiting, or abdominal pain)
Measured: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).
Number of Confirmed Peripheral HAE Attacks
A prespecified secondary endpoint analyzed confirmed attacks by anatomical location; peripheral attacks included any with peripheral symptoms only (i.e. peripheral swelling or erythema marginatum).
Measured: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).
HAE Attacks Requiring Treatment
A prespecified secondary endpoint analyzed the number of attacks requiring treatment with acute HAE medication (Berinert, Firazyr, Cinryze or Ruconest)
Measured: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).
HAE Disease Activity - Modified Angioedema Activity Score
Activity of disease (i.e. disease severity) was assessed using a modified Angioedema Activity Score (AAS). The relevant endpoint for this study was the total modified AAS score, defined as the sum of the individual scores for 4 AAS domains (daily activities, appearance, physical discomfort, and overall severity) for all subject-reported attacks reported during the treatment period. Individual domain scores were based on answers to questions each of which had 4 possible responses scored 0-3 (0 - no impact; 1-3 - increasing levels of impact). The total modified AAS score per attack could range from 0 to 12; lower scores \& higher scores represent lower \& higher disease activities, respectively. However, the overall total modified AAS score reported for this study included the total scores for all subject-reported attacks, therefore the upper limit of the range was subject-specific. The statistical analysis of the total modified AAS scores for the treatment period is presented below.
Measured: 28-day treatment period + 1 day
Angioedema Quality of Life (AE-QoL)
Quality of Life (QoL) specific to hereditary angioedema (HAE) was assessed at baseline and Day 29 by a questionnaire (i.e. AE-QoL) consisting of 17 questions that spanned 4 domains (functioning, fatigue/mood, fear/shame, and nutrition). Each AE-QoL question had 5 answer options (scored 1-5), with lower and higher scores indicting less and more adverse impact, respectively. Per-subject scores for each domain were computed using the appropriate scoring algorithm applied to the question response scores for each domain. Per-subject total scores (including all 4 domains) were similarly computed using the question response scores for all 17 questions. The outputs from the scoring algorithm were normalized on a scale ranging from 0 (less adverse impact) to 100 (most adverse impact). The statistical analysis of the AE-QoL total score change from baseline to Day 29 is presented below.
Measured: The subject-completed AE-QoL was administered at baseline (Day 1) and at Day 29
DASS (Depression, Anxiety and Stress Scales)
The Depression, Anxiety \& Stress Scale (DASS) was used to measure the negative emotional states of depression, anxiety \& stress. This assessment was based on a DASS questionnaire administered at baseline, Day 14 \& Day 29. The questionnaire consisted of 3 DASS scales (depression, anxiety \& stress) containing 14 items each on a scale of 0 to 3 (0, did not apply to me at all; 1, applied to me to some degree/some of the time; 2, applied to me to a considerable degree/a good part of the time; 3, applied to me very much or most of the time). Per-subject scores for the depression, anxiety \& stress scales were obtained by summing the scores for the appropriate questionnaire items for the respective category. Total DASS scores were then derived as the sum of the 3 individual scales \& ranged from 0 to 126. Higher \& lower total scores are associated with more \& less adverse impact, respectively. The statistical analysis of the total DASS score change from baseline to Day 29 is presented below.
Measured: The DASS was administered at baseline (Day 1), Day 14, and Day 29.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2016 (estimated)
- Study startAug 2016
- Primary completionAug 2017
- Study completionAug 2017
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 (3)Papers the sponsor has linked to this study.
- Other trials for Hereditary Angioedema (HAE)Studies 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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioCryst Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Emel Aygören-Pürsün, MD, Principal investigator, University Hospital Frankfurt Goethe University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02870972
- Sponsor's protocol ID
- BCX7353-203
- Acronym
- APeX-1
- Status last verified
- Mar 2021
- First submitted
- 10 Aug 2016
- Last updated
- 23 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
Farkas H, Balla Z. A review of berotralstat for the treatment of hereditary angioedema. Expert Rev Clin Immunol. 2023 Feb;19(2):145-153. doi: 10.1080/1744666X.2023.2150611. Epub 2022 Nov 29.
PubMed 36408587Beard 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 36326435Aygoren-Pursun E, Bygum A, Grivcheva-Panovska V, Magerl M, Graff J, Steiner UC, Fain O, Huissoon A, Kinaciyan T, Farkas H, Lleonart R, Longhurst HJ, Rae W, Triggiani M, Aberer W, Cancian M, Zanichelli A, Smith WB, Baeza ML, Du-Thanh A, Gompels M, Gonzalez-Quevedo T, Greve J, Guilarte M, Katelaris C, Dobo S, Cornpropst M, Clemons D, Fang L, Collis P, Sheridan W, Maurer M, Cicardi M. Oral Plasma Kallikrein Inhibitor for Prophylaxis in Hereditary Angioedema. N Engl J Med. 2018 Jul 26;379(4):352-362. doi: 10.1056/NEJMoa1716995.
PubMed 30044938
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Dose-ranging, Parallel-group Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BCX7353 as a Preventative Treatment to Reduce the Frequency of Attacks in Subjects With Hereditary Angioedema
- ClinicalTrials.gov ID
- NCT02870972
- Acronym / sponsor ID
- APeX-1 / BCX7353-203
- Conditions
- Hereditary Angioedema (HAE)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- BioCryst PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Aug 2016 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 18 Aug 2016 (estimated)
- Results
- Posted 4 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 3-part study will evaluate the safety and efficacy of an oral treatment, BCX7353, in preventing angioedema attacks in subjects with hereditary angioedema (HAE). In Part 1 of the study, eligible subjects will be randomized to receive oral BCX7353 or placebo for 4 weeks. Assuming successful completion of Part 1, additional subjects will be randomized in Part 2 to one of 2 lower doses of BCX7353 or placebo. Part 3 will enroll additional subjects into one of three doses of BCX7353 or placebo. The study will compare the number of acute attacks in each treatment group, as well as a number of other clinical and pharmacologic outcomes, and the safety and tolerability of each dose of BCX7353 compared to placebo.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part 1: BCX7353 350 mg once daily | Experimental | Drug: BCX7353BCX7353 capsules, 350 mg dose administered once per day for 28 days |
| Parts 2 and 3: BCX7353 250 mg once daily | Experimental | Drug: BCX7353BCX7353 capsules, 250 mg dose administered once per day for 28 days |
| Parts 2 and 3: BCX7353 125 mg once daily | Experimental | Drug: BCX7353BCX7353 capsules, 125 mg dose administered once per day for 28 days |
| Parts 1, 2 and 3: Placebo | Placebo comparator | Drug: PlaceboPlacebo capsules, administered once per day for 28 days |
| Part 3: BCX7353 62.5 mg once daily | Experimental | Drug: BCX7353BCX7353 capsules, 62.5 mg dose administered once per day for 28 days |
Who may qualify
- Ages
- 18 to 70 years
- 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
- Access to acute attack medications
- Sexually active women of child-bearing potential and sexually active men must utilize 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, 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
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 |
|---|---|---|
| BCX7353Plasma kallikrein inhibitor | Drug | Part 1: BCX7353 350 mg once daily, Part 3: BCX7353 62.5 mg once daily, Parts 2 and 3: BCX7353 125 mg once daily, Parts 2 and 3: BCX7353 250 mg once daily |
| Placebo | Drug | Parts 1, 2 and 3: Placebo |
Primary outcome
Number of Confirmed HAE Attacks
Time frame: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).
Efficacy was evaluated by the number of acute angioedema attacks. To ensure that consistent, objective assessments were used in accepting subject-reported attack data, a panel of expert physicians in the treatment of HAE patients adjudicated all subject-reported attacks prior to their inclusion in primary efficacy analyses.
Proportion of Subjects Who Were HAE Attack-free During the Entire Dosing Period
Time frame: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).
Assessment of the proportion of subjects who had no HAE attacks during the entire dosing period
6 secondary outcomes
Number of Confirmed Abdominal HAE Attacks
Time frame: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).
Number of Confirmed Peripheral HAE Attacks
Time frame: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).
HAE Attacks Requiring Treatment
Time frame: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).
HAE Disease Activity - Modified Angioedema Activity Score
Time frame: 28-day treatment period + 1 day
Angioedema Quality of Life (AE-QoL)
Time frame: The subject-completed AE-QoL was administered at baseline (Day 1) and at Day 29
DASS (Depression, Anxiety and Stress Scales)
Time frame: The DASS was administered at baseline (Day 1), Day 14, and Day 29.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36408587Farkas H, Balla Z. A review of berotralstat for the treatment of hereditary angioedema. Expert Rev Clin Immunol. 2023 Feb;19(2):145-153. doi: 10.1080/1744666X.2023.2150611. Epub 2022 Nov 29.
- 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.
- Derived from this study: PubMed 30044938Aygoren-Pursun E, Bygum A, Grivcheva-Panovska V, Magerl M, Graff J, Steiner UC, Fain O, Huissoon A, Kinaciyan T, Farkas H, Lleonart R, Longhurst HJ, Rae W, Triggiani M, Aberer W, Cancian M, Zanichelli A, Smith WB, Baeza ML, Du-Thanh A, Gompels M, Gonzalez-Quevedo T, Greve J, Guilarte M, Katelaris C, Dobo S, Cornpropst M, Clemons D, Fang L, Collis P, Sheridan W, Maurer M, Cicardi M. Oral Plasma Kallikrein Inhibitor for Prophylaxis in Hereditary Angioedema. N Engl J Med. 2018 Jul 26;379(4):352-362. doi: 10.1056/NEJMoa1716995.
- Individual participant dataSharing planned: Yes
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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.
Emel Aygören-Pürsün, MD principal investigator
University Hospital Frankfurt Goethe University
24 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BCX7353 in people with Hereditary Angioedema (HAE), run by BioCryst Pharmaceuticals at 24 sites in 11 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 23 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United Kingdom, Germany, Italy, Spain, Australia and 6 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 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.
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 4 Mar 2021). 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?
Number of Confirmed HAE Attacks (time frame: Investigators collected data from patient diaries from the first day of dosing through to Day 29 or last day of dosing +24 hrs (the effective dosing period).). The study lists 2 primary outcomes in all. 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 NCT02870972, which also lists 3 linked publications.
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 23 Mar 2021.