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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/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
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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
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Secondary ID [1]
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BCX7353-203
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Universal Trial Number (UTN)
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Trial acronym
APeX-1
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Hereditary Angioedema (HAE)
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Condition category
Condition code
Cardiovascular
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Diseases of the vasculature and circulation including the lymphatic system
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Blood
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Other blood disorders
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Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Confirmed HAE Attacks
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Assessment method [1]
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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.
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Timepoint [1]
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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).
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Primary outcome [2]
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Proportion of Subjects Who Were HAE Attack-free During the Entire Dosing Period
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Assessment method [2]
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Assessment of the proportion of subjects who had no HAE attacks during the entire dosing period
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Timepoint [2]
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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).
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Secondary outcome [1]
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Number of Confirmed Abdominal HAE Attacks
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Assessment method [1]
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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)
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Timepoint [1]
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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).
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Secondary outcome [2]
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Number of Confirmed Peripheral HAE Attacks
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Assessment method [2]
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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).
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Timepoint [2]
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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).
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Secondary outcome [3]
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HAE Attacks Requiring Treatment
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Assessment method [3]
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A prespecified secondary endpoint analyzed the number of attacks requiring treatment with acute HAE medication (Berinert, Firazyr, Cinryze or Ruconest)
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Timepoint [3]
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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).
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Secondary outcome [4]
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HAE Disease Activity - Modified Angioedema Activity Score
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Assessment method [4]
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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.
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Timepoint [4]
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28-day treatment period + 1 day
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Secondary outcome [5]
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Angioedema Quality of Life (AE-QoL)
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Assessment method [5]
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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.
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Timepoint [5]
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The subject-completed AE-QoL was administered at baseline (Day 1) and at Day 29
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Secondary outcome [6]
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DASS (Depression, Anxiety and Stress Scales)
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Assessment method [6]
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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.
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Timepoint [6]
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The DASS was administered at baseline (Day 1), Day 14, and Day 29.
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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
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Minimum age
18
Years
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Maximum age
70
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Prevention
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/08/2016
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/08/2017
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Sample size
Target
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Accrual to date
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Final
75
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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- Adelaide
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Recruitment hospital [2]
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- Campbelltown
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Recruitment postcode(s) [1]
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- Adelaide
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Recruitment postcode(s) [2]
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- Campbelltown
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Recruitment outside Australia
Country [1]
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Austria
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State/province [1]
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Graz
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Austria
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State/province [2]
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Vienna
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Canada
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Quebec City
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Canada
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Toronto
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Denmark
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State/province [5]
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Odense
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Germany
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State/province [6]
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Berlin
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Country [7]
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Germany
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State/province [7]
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Frankfurt
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Country [8]
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Germany
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State/province [8]
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Ulm
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Country [9]
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Hungary
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State/province [9]
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Budapest
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Italy
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Milano
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Italy
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State/province [11]
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Padova
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Italy
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State/province [12]
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Salerno
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North Macedonia
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State/province [13]
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Skopje
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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State/province [16]
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Sevilla
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Country [17]
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Switzerland
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Zürich
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Country [18]
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United Kingdom
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Brimingham
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United Kingdom
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Bristol
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Country [20]
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United Kingdom
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London
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United Kingdom
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Oxford
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Country [22]
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United Kingdom
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State/province [22]
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Southampton
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
BioCryst Pharmaceuticals
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Address
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02870972
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Emel Aygören-Pürsün, MD
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Address
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University Hospital Frankfurt Goethe University
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Phone
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Fax
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Email
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Contact person for public queries
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02870972
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