Hereditary Angioedema (HAE)Phase 2NCT03240133

Study of BCX7353 as a Treatment for Attacks of Hereditary Angioedema

A Phase 2 study testing BCX7353 in people with Hereditary Angioedema (HAE), run by BioCryst Pharmaceuticals at 24 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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: 58 participants
Where: 24 sitesin 12 countries
Study dates: 31 Jul 2017to 29 Jan 2019
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

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.

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.
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.

Trial locations and contacts

24 sites in 12 countries.

Country

City, postcode or hospital

24 sites in 12 countries

United Kingdom7 sites

Study Center
Birmingham
Study Center
Bristol
Study Center
Cambridge
Study Center
London
Study Center
Manchester
Study Center
Plymouth
Study Center
Southampton

Other trials in United Kingdom

Israel3 sites

Study Center
Ashkelon
Study Center
Tel Aviv
Study Center
Tel HaShomer

Other trials in Israel

Italy3 sites

Study Center
Milan
Study center
Padova
Study Center
Salerno

Other trials in Italy

France2 sites

Study Center
Grenoble
Study Center
Lille

Other trials in France

Germany2 sites

Study Center
Berlin
Study Center
Frankfurt

Other trials in Germany

Austria1 site

Study Center
Graz

Other trials in Austria

Denmark1 site

Study Center
Odense

Other trials in Denmark

Hungary1 site

Study Center
Budapest

Other trials in Hungary

North Macedonia1 site

Study Center
Skopje

Other trials in North Macedonia

Poland1 site

Study Center
Krakow

Other trials in Poland

Romania1 site

Study Center
Târgu Mureş

Other trials in Romania

Switzerland1 site

Study Center
Zurich

Other trials in Switzerland

About this study

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

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.

Conditions: Hereditary Angioedema (HAE)
Being tested: BCX7353, Placebo
Keywords: HAE, hereditary angioedema, kallikrein inhibitor, plasma kallikrein
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
oral liquid formulation
PlaceboDrug
oral liquid formulation to match BCX7353

Study groups in NCT03240133
Study group	Role	What they receive
Part1: BCX7353 750 mg	Experimental	Not described Receives: Drug: BCX7353
Part 2: BCX7353 500 mg	Experimental	Not described Receives: Drug: BCX7353
Part 3: BCX7353 250 mg	Experimental	Not described Receives: Drug: BCX7353
Parts 1, 2 and 3: placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Mean composite VAS for HAE attack symptoms severity prior to IMP treatment and 4 hours post-dose
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.
Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Jul 201729 Jan 2019

First posted4 Aug 2017
Study start31 Jul 2017
Primary completion29 Jan 2019
Study completion29 Jan 2019

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 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: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 58 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03240133
Sponsor's protocol ID: BCX7353-202
Status last verified: Mar 2021
First submitted: 2 Aug 2017
Last updated: 1 Apr 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

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 36408587

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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RecruitingObservational study
A Study of Takhzyro in Teenagers and Adults With Hereditary Angioedema (HAE) in South Korea
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HAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE)
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RecruitingPhase 3
Study of IV Human Plasma-derived C1 Esterase Inhibitor Concentrate in Patients With Congenital C1-INH Deficiency for Treatment and Pre-procedure Preventing of Acute Hereditary Angioedema Attacks
Acute Hereditary Angio Edema
Active, not recruitingPhase 1/2
NTLA-2002 in Adults With Hereditary Angioedema (HAE)
Hereditary Angioedema

All Hereditary Angioedema (HAE) trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03240133
Acronym / sponsor ID: BCX7353-202
Conditions: Hereditary Angioedema (HAE)
Keywords: HAE, hereditary angioedema, kallikrein inhibitor, plasma kallikrein
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 58 participants (actual)
Lead sponsor: BioCryst PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 31 Jul 2017 (actual)
Primary completion: 29 Jan 2019 (actual)
Study completion: 29 Jan 2019 (actual)
First posted: 4 Aug 2017 (actual)
Results: Posted 1 Apr 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Part1: BCX7353 750 mg	Experimental	Drug: BCX7353
Part 2: BCX7353 500 mg	Experimental	Drug: BCX7353
Part 3: BCX7353 250 mg	Experimental	Drug: BCX7353
Parts 1, 2 and 3: placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (8 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
BCX7353oral liquid formulation	Drug	Part 2: BCX7353 500 mg, Part 3: BCX7353 250 mg, Part1: BCX7353 750 mg
Placebooral liquid formulation to match BCX7353	Drug	Parts 1, 2 and 3: placebo

Primary outcome

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.
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.

Results and safety

Results posted to the registry on 1 Apr 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: Berotralstat (750 mg) & Placebo Treated HAE Attacks	33	30
Part 2: Berotralstat (500 mg) & Placebo Treated HAE Attacks	14	11
Part 3: Berotralstat (250 mg) & Placebo Treated HAE Attacks	11	10

Primary outcome: 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. Mean (Standard Deviation). Unit: VAS score - millimeters

Measure	Part 1: Berotralstat 750 mg - Predose n = 33	Part 1: Placebo - Pre-dose n = 28	Part 1: Berotralstat 750 mg - 4hr Post-dose n = 33	Part 1: Placebo - 4hr Post-dose n = 28	Part 2: Berotralstat 500 mg - Predose n = 14	Part 2: Placebo - Pre-dose n = 9	Part 2: Berotralstat 500 mg - 4hr Post-dose n = 14	Part 2: Placebo - 4hr Post-dose n = 9	Part 3: Berotralstat 250 mg - Predose n = 11	Part 3: Placebo - Pre-dose n = 11	Part 3: Berotralstat 250 mg - 4hr Post-dose n = 11	Part 3: Placebo - 4hr Post-dose n = 11
Value	13.96 (9.84)	15.04 (11.90)	10.54 (11.39)	18.42 (14.19)	17.69 (15.25)	13.48 (16.11)	11.31 (15.75)	9.26 (11.53)	14.57 (11.78)	11.33 (10.17)	10.92 (10.31)	9.21 (9.67)

Part 1: Berotralstat 750 mg - Predose vs Part 1: Placebo - Pre-dose vs Part 1: Berotralstat 750 mg - 4hr Post-dose vs Part 1: Placebo - 4hr Post-dose: Difference in Least Square Means: -6.98 (95% CI -11.37 to -2.6), p = 0.0024, Mixed effect linear model
Part 2: Berotralstat 500 mg - Predose vs Part 2: Placebo - Pre-dose vs Part 2: Berotralstat 500 mg - 4hr Post-dose vs Part 2: Placebo - 4hr Post-dose: Difference in Least Square Means: -2.1 (95% CI -11.49 to 7.29), p = 0.6424, Mixed effect linear model
Part 3: Berotralstat 250 mg - Predose vs Part 3: Placebo - Pre-dose vs Part 3: Berotralstat 250 mg - 4hr Post-dose vs Part 3: Placebo - 4hr Post-dose: Difference in Least Square Means: 0.57 (95% CI -4.9 to 6.03), p = 0.8283, Mixed effect linear model

Population analysed: The number of participants analyzed in each analysis set corresponds to number of HAE attacks treated with placebo or berotralstat.

Primary outcome: Percentage of Attacks Treated With Standard of Care Acute Attack Medication (SOC-Rx) Through 24 Hours

Time frame: 24 hours. Number. Unit: Percentage attacks treated with SOC-Rx

Measure	Part 1: Berotralstat 750 mg n = 33	Part 1: Placebo n = 28	Part 2: Berotralstat 500 mg n = 14	Part 2: Placebo n = 9	Part 3: Berotralstat 250 mg n = 11	Part 3: Placebo n = 11
Value	29.7	61.3	32.0	45.5	38.1	45.5

Part 1: Berotralstat 750 mg vs Part 1: Placebo: Odds Ratio (OR): 0.196 (95% CI 0.069 to 0.559), p = 0.0029, logistic mixed effect model
Part 2: Berotralstat 500 mg vs Part 2: Placebo: Odds Ratio (OR): 0.472 (95% CI 0.074 to 2.988), p = 0.4048, logistic mixed effect model
Part 3: Berotralstat 250 mg vs Part 3: Placebo: Odds Ratio (OR): 0.587 (95% CI 0.073 to 4.733), p = 0.5984, logistic mixed effect model

Adverse events

Time frame: Adverse events (AEs) were collected from informed consent signature until 16 to 19 days after the 3rd or final HAE attack treated with IMP. As the HAE attack frequency varied between subjects, subject duration of study participation and therefore the duration over which AEs were collected was dependent on attack frequency and therefore variable. The maximum period over which AEs were collected was 281 days.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part1: Berotralstat 750 mg	0 of 33 (0%)	12 of 33 (36.4%)	0 of 33
Part 2: Berotralstat 500 mg	1 of 14 (7.1%)	8 of 14 (57.1%)	0 of 14
Part 3: Berotralstat 250 mg	0 of 11 (0%)	7 of 11 (63.6%)	0 of 11
Parts 1, 2 and 3: Placebo	1 of 53 (1.9%)	17 of 53 (32.1%)	0 of 53

Limitations and caveats (from the sponsor): In this interim clinical study report (CSR), the VAS change from pre-dose at 4 hours and the proportion of attacks requiring SOC-Rx through the 24 hour post dose were discussed. Assessment of other efficacy endpoints were to be discussed in a final CSR, but this is no longer planned due to a decision to not proceed further with trials of acute treatment of HAE attacks with berotralstat.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 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.

Related trials for Hereditary Angioedema (HAE)

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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.

Hilary Longhurst, MBBS, PhD principal investigator

Barts & The London NHS Trust

24 sites in 12 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 12 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 8 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 1 Apr 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, Israel, Italy, France, Germany and 7 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 1 Apr 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?

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). 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 NCT03240133, 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 1 Apr 2021.