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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02870972




Registration number
NCT02870972
Ethics application status
Date submitted
10/08/2016
Date registered
18/08/2016
Date last updated
23/03/2021

Titles & IDs
Public title
Efficacy and Safety of BCX7353 to Prevent Angioedema Attacks in Subjects With Hereditary Angioedema
Scientific 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
Secondary ID [1] 0 0
BCX7353-203
Universal Trial Number (UTN)
Trial acronym
APeX-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hereditary Angioedema (HAE) 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BCX7353
Treatment: Drugs - Placebo

Experimental: Part 1: BCX7353 350 mg once daily - BCX7353 capsules, 350 mg dose administered once per day for 28 days

Experimental: Parts 2 and 3: BCX7353 250 mg once daily - BCX7353 capsules, 250 mg dose administered once per day for 28 days

Experimental: Parts 2 and 3: BCX7353 125 mg once daily - BCX7353 capsules, 125 mg dose administered once per day for 28 days

Placebo Comparator: Parts 1, 2 and 3: Placebo - Placebo capsules, administered once per day for 28 days

Experimental: Part 3: BCX7353 62.5 mg once daily - BCX7353 capsules, 62.5 mg dose administered once per day for 28 days


Treatment: Drugs: BCX7353
Plasma kallikrein inhibitor

Treatment: Drugs: Placebo


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
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).
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
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 outcome [1] 0 0
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)
Timepoint [1] 0 0
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 outcome [2] 0 0
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).
Timepoint [2] 0 0
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 outcome [3] 0 0
HAE Attacks Requiring Treatment - A prespecified secondary endpoint analyzed the number of attacks requiring treatment with acute HAE medication (Berinert, Firazyr, Cinryze or Ruconest)
Timepoint [3] 0 0
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 outcome [4] 0 0
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.
Timepoint [4] 0 0
28-day treatment period + 1 day
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
The subject-completed AE-QoL was administered at baseline (Day 1) and at Day 29
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
The DASS was administered at baseline (Day 1), Day 14, and Day 29.

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Campbelltown
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Campbelltown
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Graz
Country [2] 0 0
Austria
State/province [2] 0 0
Vienna
Country [3] 0 0
Canada
State/province [3] 0 0
Quebec City
Country [4] 0 0
Canada
State/province [4] 0 0
Toronto
Country [5] 0 0
Denmark
State/province [5] 0 0
Odense
Country [6] 0 0
Germany
State/province [6] 0 0
Berlin
Country [7] 0 0
Germany
State/province [7] 0 0
Frankfurt
Country [8] 0 0
Germany
State/province [8] 0 0
Ulm
Country [9] 0 0
Hungary
State/province [9] 0 0
Budapest
Country [10] 0 0
Italy
State/province [10] 0 0
Milano
Country [11] 0 0
Italy
State/province [11] 0 0
Padova
Country [12] 0 0
Italy
State/province [12] 0 0
Salerno
Country [13] 0 0
North Macedonia
State/province [13] 0 0
Skopje
Country [14] 0 0
Spain
State/province [14] 0 0
Barcelona
Country [15] 0 0
Spain
State/province [15] 0 0
Madrid
Country [16] 0 0
Spain
State/province [16] 0 0
Sevilla
Country [17] 0 0
Switzerland
State/province [17] 0 0
Zürich
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Brimingham
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Bristol
Country [20] 0 0
United Kingdom
State/province [20] 0 0
London
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Oxford
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
BioCryst Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
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.
Trial website
https://clinicaltrials.gov/show/NCT02870972
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Emel Aygören-Pürsün, MD
Address 0 0
University Hospital Frankfurt Goethe University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications