A Long Term Safety Study of BCX7353 in Hereditary Angioedema

Hereditary Angioedema Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03472040
• Other study ID #: BCX7353-204
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: February 16, 2018
• Est. completion date: April 27, 2022

Study information

• Verified date: May 2023
• Source: BioCryst Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 387
• Est. completion date: April 27, 2022
• Est. primary completion date: April 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Angioedema
• HAE
• Hereditary Angioedema
• Prophylaxis

Intervention

Drug:
• BCX7353
BCX7353 mg oral capsules administered once daily

Locations

Country	Name	City	State
Australia	Study Center	Adelaide
Australia	Study Center	Campbelltown
Australia	Study Center	Camperdown
Australia	Study Center	Melbourne
Australia	Study Center	Murdoch
Australia	Study Center	Nedlands
Austria	Study Center	Graz
Austria	Study Center	Vienna
Denmark	Study Center	Odense
France	Study Center	Grenoble
France	Study Center	Lille
France	Study Center	Paris
Germany	Study Center	Berlin
Germany	Study Center	Frankfurt
Germany	Study Center	Ulm
Hong Kong	Study Center	Central
Hungary	Study Center	Budapest
Israel	Study Center	Ashkelon
Israel	Study Center	Haifa
Israel	Study Center	Tel Aviv
Israel	Study Center	Tel HaShomer
Italy	Study Center	Milan
Italy	Study Center	Padova
Italy	Study Center	Salerno
Korea, Republic of	Study Center	Daegu
Korea, Republic of	Study Center	Donggu
Korea, Republic of	Study Center	Gyeonggi-do
Korea, Republic of	Study Center	Seoul
New Zealand	Study Center	Auckland
New Zealand	Study Center	Wellington
North Macedonia	Study Center	Skopje
Poland	Study Center	Kraków
Serbia	Study Center	Belgrade
Serbia	Study Center	Niš
Slovakia	Study Center	Martin
South Africa	Study Center	Cape Town
Spain	Study Center	Barcelona
Spain	Study Center	Madrid
Switzerland	Study Center	Zürich
United Kingdom	Study center	Birmingham
United Kingdom	Study Center	Bristol
United Kingdom	Study Center	Cambridge
United Kingdom	Study Center	London
United Kingdom	Study Center	Plymouth
United Kingdom	Study Center	Southampton
United States	Study Center	Ann Arbor	Michigan
United States	Study Center	Austin	Texas
United States	Study Center	Bentonville	Arkansas
United States	Study Center	Birmingham	Alabama
United States	Study Center	Boston	Massachusetts
United States	Study Center	Centennial	Colorado
United States	Study Center	Charlotte	North Carolina
United States	Study Center	Chevy Chase	Maryland
United States	Study Center	Cincinnati	Ohio
United States	Study Center	Clackamas	Oregon
United States	Study Center	Colorado Springs	Colorado
United States	Study Center	Columbus	Ohio
United States	Study Center	Dallas	Texas
United States	Study Center	Durham	North Carolina
United States	Study Center	East Providence	Rhode Island
United States	Study Center	Evansville	Indiana
United States	Study Center	Grand Rapids	Michigan
United States	Study Center	Greer	South Carolina
United States	Study Center	Happy Valley	Oregon
United States	Study Center	Hershey	Pennsylvania
United States	Study Center	Indianapolis	Indiana
United States	Study Center	Irving	Texas
United States	Study Center	Lincoln	Nebraska
United States	Study Center	Little Rock	Arkansas
United States	Study Center	Louisville	Kentucky
United States	Study Center	Madison	Mississippi
United States	Study Center	Marietta	Georgia
United States	Study Center	Milwaukee	Wisconsin
United States	Study Center	Murray	Utah
United States	Study Center	Normal	Illinois
United States	Study Center	Overland Park	Kansas
United States	Study Center	Rochester	Minnesota
United States	Study Center	Saint Louis	Missouri
United States	Study Center	San Antonio	Texas
United States	Study Center	San Diego	California
United States	Study Center	Scottsdale	Arizona
United States	Study Center	Seattle	Washington
United States	Study Center	Spokane	Washington
United States	Study Center	Tampa	Florida
United States	Study Center	Walnut Creek	California
United States	Study Center	Waterbury	Connecticut
United States	Study Center	Wheat Ridge	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
BioCryst Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Denmark,  France,  Germany,  Hong Kong,  Hungary,  Israel,  Italy,  Korea, Republic of,  New Zealand,  North Macedonia,  Poland,  Serbia,  Slovakia,  South Africa,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety & Tolerability	The number and percentage of subjects with treatment-emergent adverse events.	Up to 96 weeks (US) / 216 weeks (Rest of World (ROW)).
Secondary	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.	Up to 96 weeks (US) / 216 weeks (ROW)
Secondary	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.	Up to 96 weeks (US) / 216 weeks (ROW)
Secondary	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.	Up to 96 weeks (US) / 216 weeks (ROW)
Secondary	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.	Up to 96 weeks (US) / 216 weeks (ROW)