Back to resultsA Long Term Safety Study of BCX7353 in Hereditary Angioedema (APeX-S)
Primary Purpose
Hereditary Angioedema, HAE, Prophylaxis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BCX7353
Sponsored by
About this trial
This is an interventional prevention trial for Hereditary Angioedema focused on measuring BCX7353, Hereditary Angioedema, HAE
Eligibility Criteria
Key Inclusion Criteria:
- Subjects with HAE Type I or II who either have participated in a previous BCX7353 study or, in selected countries, in the opinion of the Investigator are expected to derive benefit from an oral treatment for the prevention of angioedema attacks.
- Access to appropriate medication for treatment of acute attacks
- Acceptable effective contraception
- Written informed consent
Key Exclusion Criteria:
- Pregnancy or breast-feeding
- Any clinically significant medical condition or medical history that, in the opinion of the Investigator or Sponsor, would interfere with the subject's safety or ability to participate in the study
- Any laboratory parameter abnormality that, in the opinion of the Investigator, is clinically significant and relevant for this study
- Discontinuation of study drug due to a hypersensitivity reaction BCX7353 in a prior study
- Severe hypersensitivity to multiple medicinal products or severe hypersensitivity/ anaphylaxis with unclear etiology
- Unacceptable noncompliance in a previous BCX7353 study (if applicable) as assessed by the Sponsor or Investigator
- Investigational drug exposure, other than BCX7353, within 30 days prior to the screening visit (or baseline if no screening visit)
Sites / Locations
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Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BCX7353 150 mg once daily
Arm Description
Outcomes
Primary Outcome Measures
Safety & Tolerability
The number and percentage of subjects with treatment-emergent adverse events.
Secondary Outcome Measures
Incidence of Acute Attacks of Angioedema in Subjects During Treatment
Number of 'adjusted' attacks were assessed. Adjusted attacks included at least 1 symptom of swelling, had a response of 'no' to the diary question, 'In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (i.e., allergic reaction, viral cold etc.)?', and were considered unique (attack began > 24 hours from the end of the prior attack). Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.
The Durability of Response to Treatment
To evaluate if the rate of attacks remains consistent (durable) over time, the monthly attack rate was assessed at 0 to 24 weeks, 24 to 48 weeks, 48 to 96 weeks and 96 weeks until the end of the study. Monthly attack rate was defined as the total number of adjusted HAE attacks experienced during the treatment period adjusted for the length of a month (defined as 28 days) and the number of days the subject was on treatment during that month.
Patient Reported Quality of Life (QoL) During Treatment
Quality of Life (QoL) specific to hereditary angioedema (HAE) was assessed at baseline and at each study visit until the end of the study. The questionnaire (i.e. AE-QoL) consisted of 17 questions spanning 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 Mean change from baseline (CFB) in AE-QoL total score over time is presented below.
Patient's Satisfaction With Medication During Long Term Administration of Berotralstat
The Treatment Satisfaction Questionnaire for Medication (TSQM) was completed by subjects at baseline and at each study visit until the end of the study. TSQM scores consisted of 14 items of which 13 items were made up of 3 specific scales (Effectiveness, Side Effects, and Convenience) and 1 global satisfaction scale (Global Satisfaction). At baseline, TSQM questionnaires were completed based on subject's satisfaction with usual medications. At all other time points for collection of TSQM, subjects were asked about their level of satisfaction or dissatisfaction with the study drug. Scale scores were calculated for each scale and were transformed into scores ranging from 0 to 100, with higher scores indicating higher satisfaction. TSQM score and corresponding change from baseline values were calculated at each visit. Note: Subjects in Hong Kong did not complete the TSQM.
Full Information
NCT ID
NCT03472040
First Posted
February 27, 2018
Last Updated
May 23, 2023
Sponsor
BioCryst Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03472040
Brief Title
A Long Term Safety Study of BCX7353 in Hereditary Angioedema
Acronym
APeX-S
Official Title
An Open-label Study to Evaluate the Long-term Safety of Daily Oral BCX7353 in Subjects With Type I and II Hereditary Angioedema
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
February 16, 2018 (Actual)
Primary Completion Date
April 27, 2022 (Actual)
Study Completion Date
April 27, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioCryst Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open-label study to evaluate the long term safety and effectiveness of oral treatment with BCX7353 in preventing acute angioedema attacks in patients with Type I and Type II Hereditary Angioedema (HAE).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema, HAE, Prophylaxis
Keywords
BCX7353, Hereditary Angioedema, HAE
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
387 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BCX7353 150 mg once daily
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BCX7353
Intervention Description
BCX7353 mg oral capsules administered once daily
Primary Outcome Measure Information:
Title
Safety & Tolerability
Description
The number and percentage of subjects with treatment-emergent adverse events.
Time Frame
Up to 96 weeks (US) / 216 weeks (Rest of World (ROW)).
Secondary Outcome Measure Information:
Title
Incidence of Acute Attacks of Angioedema in Subjects During Treatment
Description
Number of 'adjusted' attacks were assessed. Adjusted attacks included at least 1 symptom of swelling, had a response of 'no' to the diary question, 'In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (i.e., allergic reaction, viral cold etc.)?', and were considered unique (attack began > 24 hours from the end of the prior attack). Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.
Time Frame
Up to 96 weeks (US) / 216 weeks (ROW)
Title
The Durability of Response to Treatment
Description
To evaluate if the rate of attacks remains consistent (durable) over time, the monthly attack rate was assessed at 0 to 24 weeks, 24 to 48 weeks, 48 to 96 weeks and 96 weeks until the end of the study. Monthly attack rate was defined as the total number of adjusted HAE attacks experienced during the treatment period adjusted for the length of a month (defined as 28 days) and the number of days the subject was on treatment during that month.
Time Frame
Up to 96 weeks (US) / 216 weeks (ROW)
Title
Patient Reported Quality of Life (QoL) During Treatment
Description
Quality of Life (QoL) specific to hereditary angioedema (HAE) was assessed at baseline and at each study visit until the end of the study. The questionnaire (i.e. AE-QoL) consisted of 17 questions spanning 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 Mean change from baseline (CFB) in AE-QoL total score over time is presented below.
Time Frame
Up to 96 weeks (US) / 216 weeks (ROW)
Title
Patient's Satisfaction With Medication During Long Term Administration of Berotralstat
Description
The Treatment Satisfaction Questionnaire for Medication (TSQM) was completed by subjects at baseline and at each study visit until the end of the study. TSQM scores consisted of 14 items of which 13 items were made up of 3 specific scales (Effectiveness, Side Effects, and Convenience) and 1 global satisfaction scale (Global Satisfaction). At baseline, TSQM questionnaires were completed based on subject's satisfaction with usual medications. At all other time points for collection of TSQM, subjects were asked about their level of satisfaction or dissatisfaction with the study drug. Scale scores were calculated for each scale and were transformed into scores ranging from 0 to 100, with higher scores indicating higher satisfaction. TSQM score and corresponding change from baseline values were calculated at each visit. Note: Subjects in Hong Kong did not complete the TSQM.
Time Frame
Up to 96 weeks (US) / 216 weeks (ROW)
10. Eligibility
Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Subjects with HAE Type I or II who either have participated in a previous BCX7353 study or, in selected countries, in the opinion of the Investigator are expected to derive benefit from an oral treatment for the prevention of angioedema attacks.
Access to appropriate medication for treatment of acute attacks
Acceptable effective contraception
Written informed consent
Key Exclusion Criteria:
Pregnancy or breast-feeding
Any clinically significant medical condition or medical history that, in the opinion of the Investigator or Sponsor, would interfere with the subject's safety or ability to participate in the study
Any laboratory parameter abnormality that, in the opinion of the Investigator, is clinically significant and relevant for this study
Discontinuation of study drug due to a hypersensitivity reaction BCX7353 in a prior study
Severe hypersensitivity to multiple medicinal products or severe hypersensitivity/ anaphylaxis with unclear etiology
Unacceptable noncompliance in a previous BCX7353 study (if applicable) as assessed by the Sponsor or Investigator
Investigational drug exposure, other than BCX7353, within 30 days prior to the screening visit (or baseline if no screening visit)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henriette Farkas, MD
Organizational Affiliation
Semmelweis University, Budapest, Hungary
Official's Role
Principal Investigator
Facility Information:
Facility Name
Study Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Study Center
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
Study Center
City
Bentonville
State/Province
Arkansas
ZIP/Postal Code
72712
Country
United States
Facility Name
Study Center
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Study Center
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Study Center
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
Study Center
City
Centennial
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
Study Center
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
Study Center
City
Wheat Ridge
State/Province
Colorado
ZIP/Postal Code
80033
Country
United States
Facility Name
Study Center
City
Waterbury
State/Province
Connecticut
ZIP/Postal Code
06708
Country
United States
Facility Name
Study Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Study Center
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Facility Name
Study Center
City
Normal
State/Province
Illinois
ZIP/Postal Code
61761
Country
United States
Facility Name
Study Center
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47713
Country
United States
Facility Name
Study Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Study Center
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66210
Country
United States
Facility Name
Study Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40215
Country
United States
Facility Name
Study Center
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Study Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Study Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
Study Center
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49506
Country
United States
Facility Name
Study Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Study Center
City
Madison
State/Province
Mississippi
ZIP/Postal Code
39110
Country
United States
Facility Name
Study Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Study Center
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68505
Country
United States
Facility Name
Study Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28277
Country
United States
Facility Name
Study Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Study Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45231
Country
United States
Facility Name
Study Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43235
Country
United States
Facility Name
Study Center
City
Clackamas
State/Province
Oregon
ZIP/Postal Code
97015
Country
United States
Facility Name
Study Center
City
Happy Valley
State/Province
Oregon
ZIP/Postal Code
97086
Country
United States
Facility Name
Study Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Study Center
City
East Providence
State/Province
Rhode Island
ZIP/Postal Code
02914
Country
United States
Facility Name
Study Center
City
Greer
State/Province
South Carolina
ZIP/Postal Code
29651
Country
United States
Facility Name
Study Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
Facility Name
Study Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Study Center
City
Irving
State/Province
Texas
ZIP/Postal Code
75063
Country
United States
Facility Name
Study Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Study Center
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
Study Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98115
Country
United States
Facility Name
Study Center
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Facility Name
Study Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Study Center
City
Adelaide
Country
Australia
Facility Name
Study Center
City
Campbelltown
Country
Australia
Facility Name
Study Center
City
Camperdown
Country
Australia
Facility Name
Study Center
City
Melbourne
Country
Australia
Facility Name
Study Center
City
Murdoch
Country
Australia
Facility Name
Study Center
City
Nedlands
Country
Australia
Facility Name
Study Center
City
Graz
Country
Austria
Facility Name
Study Center
City
Vienna
Country
Austria
Facility Name
Study Center
City
Odense
Country
Denmark
Facility Name
Study Center
City
Grenoble
Country
France
Facility Name
Study Center
City
Lille
Country
France
Facility Name
Study Center
City
Paris
Country
France
Facility Name
Study Center
City
Berlin
Country
Germany
Facility Name
Study Center
City
Frankfurt
Country
Germany
Facility Name
Study Center
City
Ulm
Country
Germany
Facility Name
Study Center
City
Central
Country
Hong Kong
Facility Name
Study Center
City
Budapest
Country
Hungary
Facility Name
Study Center
City
Ashkelon
Country
Israel
Facility Name
Study Center
City
Haifa
Country
Israel
Facility Name
Study Center
City
Tel Aviv
Country
Israel
Facility Name
Study Center
City
Tel HaShomer
Country
Israel
Facility Name
Study Center
City
Milan
Country
Italy
Facility Name
Study Center
City
Padova
Country
Italy
Facility Name
Study Center
City
Salerno
Country
Italy
Facility Name
Study Center
City
Daegu
Country
Korea, Republic of
Facility Name
Study Center
City
Donggu
Country
Korea, Republic of
Facility Name
Study Center
City
Gyeonggi-do
Country
Korea, Republic of
Facility Name
Study Center
City
Seoul
Country
Korea, Republic of
Facility Name
Study Center
City
Auckland
Country
New Zealand
Facility Name
Study Center
City
Wellington
Country
New Zealand
Facility Name
Study Center
City
Skopje
Country
North Macedonia
Facility Name
Study Center
City
Kraków
Country
Poland
Facility Name
Study Center
City
Belgrade
Country
Serbia
Facility Name
Study Center
City
Niš
Country
Serbia
Facility Name
Study Center
City
Martin
Country
Slovakia
Facility Name
Study Center
City
Cape Town
Country
South Africa
Facility Name
Study Center
City
Barcelona
Country
Spain
Facility Name
Study Center
City
Madrid
Country
Spain
Facility Name
Study Center
City
Zürich
Country
Switzerland
Facility Name
Study center
City
Birmingham
Country
United Kingdom
Facility Name
Study Center
City
Bristol
Country
United Kingdom
Facility Name
Study Center
City
Cambridge
Country
United Kingdom
Facility Name
Study Center
City
London
Country
United Kingdom
Facility Name
Study Center
City
Plymouth
Country
United Kingdom
Facility Name
Study Center
City
Southampton
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35820771
Citation
Riedl MA, Neville D, Cloud B, Desai B, Bernstein JA. Shared decision-making in the management of hereditary angioedema: An analysis of patient and physician perspectives. Allergy Asthma Proc. 2022 Sep 1;43(5):397-405. doi: 10.2500/aap.2022.43.220050. Epub 2022 Jul 12.
Results Reference
derived
PubMed Identifier
34161665
Citation
Farkas H, Stobiecki M, Peter J, Kinaciyan T, Maurer M, Aygoren-Pursun E, Kiani-Alikhan S, Wu A, Reshef A, Bygum A, Fain O, Hagin D, Huissoon A, Jesenak M, Lindsay K, Panovska VG, Steiner UC, Zubrinich C, Best JM, Cornpropst M, Dix D, Dobo SM, Iocca HA, Desai B, Murray SC, Nagy E, Sheridan WP. Long-term safety and effectiveness of berotralstat for hereditary angioedema: The open-label APeX-S study. Clin Transl Allergy. 2021 Jun;11(4):e12035. doi: 10.1002/clt2.12035.
Results Reference
derived
Learn more about this trial
A Long Term Safety Study of BCX7353 in Hereditary Angioedema
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