Berotralstat Treatment in Children With Hereditary Angioedema
- Conditions
- Hereditary AngioedemaPediatric
- Interventions
- Registration Number
- NCT05453968
- Lead Sponsor
- BioCryst Pharmaceuticals
- Brief Summary
The purpose of this study is to evaluate the pharmacokinetics (PK) and safety of berotralstat to determine the appropriate weight-based dose for pediatric participants 2 to \< 12 years old for prophylactic treatment to prevent attacks of hereditary angioedema (HAE).
- Detailed Description
This is a single-arm, open-label study designed to evaluate the PK and safety of berotralstat weight-based treatment for the prevention of hereditary angioedema attacks in pediatric participants 2 to \< 12 years of age. This study will consist of two treatment periods: a 12-week standard-of-care (SOC) treatment period followed by an open-label berotralstat treatment period lasting up to 144 weeks.
Participants will be enrolled into 4 dose cohorts; participant weight will be used to determine assignment to each cohort with the higher weight cohorts (Cohorts 1 and 2) enrolling first and in parallel. Safety assessments and PK modelling from all available PK data will then be used to confirm the weight bands for sequentially enrolling Cohorts 3 and 4.The effectiveness of berotralstat in this population will be summarized using descriptive statistical methods.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 29
- Male and non-pregnant, non-lactating females 2 to < 12 years of age
- Body weight ≥ 12 kg
- Clinical diagnosis of HAE
- In the opinion of the investigator, the participant would benefit from long term oral HAE prophylaxis
- Concurrent diagnosis of any other type of recurrent angioedema
- Known family history of sudden cardiac death
- Creatinine clearance using the modified Schwartz formula of ≤ 30 mL/min/1.73 m2
- Aspartate aminotransferase or alanine aminotransferase value ≥ 3 × the upper limit of the age-appropriate normal reference range value
- Clinically significant abnormal ECG including but not limited to, a corrected QT interval calculated using Fridericia's correction > 450 msec, or ventricular and/or atrial premature contractions that are more frequent than occasional, and/or as couplets or higher in grouping
- Current participation in any other investigational drug study or received another investigational drug within 30 days of enrollment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Berotralstat Berotralstat Berotralstat administered once daily in 4 dose cohorts determined by participant weight. Cohorts 1 and 2 will enroll in parallel. After 4 participants from Cohort 1 and 2, with ≥ 2 subjects from Cohort 2, have reached Week 2, Cohort 3 will open for enrollment. Cohort 4 will open for enrollment, after ≥ 4 subjects in Cohort 3 have reached Week 2. Prior to dosing Cohort 3 and 4, available PK and safety data will be reviewed to confirm it is safe to proceed and the appropriate weight bands for each. BioCryst will notify sites when Cohorts 3 and 4 are open for enrollment.
- Primary Outcome Measures
Name Time Method Pharmacokinetics: Cmax Predose and multiple timepoints up to 24 hours postdose Maximum plasma concentration of berotralstat
Pharmacokinetics: CL/F Predose and multiple timepoints up to 24 hours postdose Apparent oral clearance of berotralstat
Pharmacokinetics: AUC0-tau Predose and multiple timepoints up to 24 hours postdose Area under the plasma concentration berotralstat time curve from time zero to the end of dosing (tau)
- Secondary Outcome Measures
Name Time Method Frequency and severity of hereditary angioedema (HAE) attacks Over 48 weeks Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) Over 144 weeks
Trial Locations
- Locations (3)
Investigative Site #1
🇬🇧Bristol, United Kingdom
Investigative Site #2
🇪🇸Málaga, Spain
Investigative Site #3
🇫🇷Grenoble, France