A Long Term Safety Study of BCX7353 in Hereditary Angioedema

Study Overview
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Brief Summary
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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).

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

Conditions
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HAE, Hereditary Angioedema, Prophylaxis

Intervention / Treatment
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* Drug: BCX7353


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCX7353 150 mg once daily<br> | Drug: BCX7353<br>* BCX7353 mg oral capsules administered once daily<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCX7353, Hereditary Angioedema, HAE