A Long Term Safety Study of BCX7353 in Hereditary Angioedema (APeX-S)

An Open-label Study to Evaluate the Long-term Safety of Daily Oral BCX7353 in Subjects With Type I and II Hereditary Angioedema

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).

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema; Prophylaxis; HAE
• Intervention / Treatment: Drug: BCX7353

• Study Type: Interventional
• Enrollment (Actual): 387
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Study Center
  • Campbelltown, Australia
    • Study Center
  • Camperdown, Australia
    • Study Center
  • Melbourne, Australia
    • Study Center
  • Murdoch, Australia
    • Study Center
  • Nedlands, Australia
    • Study Center
• Austria
  • Graz, Austria
    • Study Center
  • Vienna, Austria
    • Study Center
• Denmark
  • Odense, Denmark
    • Study Center
• France
  • Grenoble, France
    • Study Center
  • Lille, France
    • Study Center
  • Paris, France
    • Study Center
• Germany
  • Berlin, Germany
    • Study Center
  • Frankfurt, Germany
    • Study Center
  • Ulm, Germany
    • Study Center
• Hong Kong
  • Central, Hong Kong
    • Study Center
• Hungary
  • Budapest, Hungary
    • Study Center
• Israel
  • Ashkelon, Israel
    • Study Center
  • Haifa, Israel
    • Study Center
  • Tel Aviv, Israel
    • Study Center
  • Tel HaShomer, Israel
    • Study Center
• Italy
  • Milan, Italy
    • Study Center
  • Padova, Italy
    • Study Center
  • Salerno, Italy
    • Study Center
• Korea, Republic of
  • Daegu, Korea, Republic of
    • Study Center
  • Donggu, Korea, Republic of
    • Study Center
  • Gyeonggi-do, Korea, Republic of
    • Study Center
  • Seoul, Korea, Republic of
    • Study Center
• New Zealand
  • Auckland, New Zealand
    • Study Center
  • Wellington, New Zealand
    • Study Center
• North Macedonia
  • Skopje, North Macedonia
    • Study Center
• Poland
  • Kraków, Poland
    • Study Center
• Serbia
  • Belgrade, Serbia
    • Study Center
  • Niš, Serbia
    • Study Center
• Slovakia
  • Martin, Slovakia
    • Study Center
• South Africa
  • Cape Town, South Africa
    • Study Center
• Spain
  • Barcelona, Spain
    • Study Center
  • Madrid, Spain
    • Study Center
• Switzerland
  • Zürich, Switzerland
    • Study Center
• United Kingdom
  • 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 Kingdom
    • Study Center
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Study Center
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Study Center
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Study Center
    • Little Rock, Arkansas, United States, 72205
      • Study Center
  • California
    • San Diego, California, United States, 92123
      • Study Center
    • Walnut Creek, California, United States, 94598
      • Study Center
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Study Center
    • Colorado Springs, Colorado, United States, 80907
      • Study Center
    • Wheat Ridge, Colorado, United States, 80033
      • Study Center
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Study Center
  • Florida
    • Tampa, Florida, United States, 33613
      • Study Center
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Study Center
  • Illinois
    • Normal, Illinois, United States, 61761
      • Study Center
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Study Center
    • Indianapolis, Indiana, United States, 46202
      • Study Center
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Study Center
  • Kentucky
    • Louisville, Kentucky, United States, 40215
      • Study Center
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Study Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Study Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Study Center
    • Grand Rapids, Michigan, United States, 49506
      • Study Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Study Center
  • Mississippi
    • Madison, Mississippi, United States, 39110
      • Study Center
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Study Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68505
      • Study Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Study Center
    • Durham, North Carolina, United States, 27705
      • Study Center
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Study Center
    • Columbus, Ohio, United States, 43235
      • Study Center
  • Oregon
    • Clackamas, Oregon, United States, 97015
      • Study Center
    • Happy Valley, Oregon, United States, 97086
      • Study Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Study Center
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Study Center
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Study Center
  • Texas
    • Austin, Texas, United States, 78731
      • Study Center
    • Dallas, Texas, United States, 75231
      • Study Center
    • Irving, Texas, United States, 75063
      • Study Center
    • San Antonio, Texas, United States, 78229
      • Study Center
  • Utah
    • Murray, Utah, United States, 84107
      • Study Center
  • Washington
    • Seattle, Washington, United States, 98115
      • Study Center
    • Spokane, Washington, United States, 99202
      • Study Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Study Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCX7353 150 mg once daily	Drug: BCX7353; BCX7353 mg oral capsules administered once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals
• Investigators: Principal Investigator: Henriette Farkas, MD, Semmelweis University, Budapest, Hungary

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2018
• Primary Completion (Actual): April 27, 2022
• Study Completion (Actual): April 27, 2022

Study Registration Dates

• First Submitted: February 27, 2018
• First Submitted That Met QC Criteria: March 14, 2018
• First Posted (Actual): March 21, 2018

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: HAE; Hereditary Angioedema; BCX7353
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Berotralstat
• Other Study ID Numbers: BCX7353-204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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