A Phase 3 Study to Evaluate the Safety and Pharmacokinetics of Berotralstat Prophylaxis in Children With Hereditary Angioedema Who Are 2 to < 12 Years of Age
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- BioCryst Pharmaceuticals
- Enrollment
- 29
- Locations
- 15
- Primary Endpoint
- Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUC0-last) of Berotralstat
Study Overview
Brief Summary
The purpose of this study is to evaluate the pharmacokinetics (PK), safety and effectiveness of berotralstat to determine the appropriate weight-based dose for pediatric participants 2 to < 12 years of age for prophylactic treatment to prevent attacks of hereditary angioedema (HAE).
Detailed Description
This is a single-arm, 3-part, open-label study designed to evaluate the PK, safety, and effectiveness of berotralstat weight-based treatment for the prevention of HAE attacks in pediatric participants 2 to < 12 years of age. Participation in this study is expected to be a minimum of 12 weeks in the standard of care (SOC) period, and in the berotralstat period, it is expected to be 12 weeks in Part 1, 36 weeks in Part 2, and 96 weeks in Part 3 of the study.
Participants were enrolled into 4 cohorts; participant weight at baseline was 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 were then used to confirm the dose and weight bands for sequentially enrolling Cohorts 3 and 4. The safety and effectiveness of berotralstat in this population was summarized using descriptive statistical methods.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 2 Years to 11 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •For subjects who are not currently receiving prophylaxis for HAE, documented history of >= 2 HAE attacks in the 6 months prior to the enrollment visit.
Exclusion Criteria
- •Concurrent diagnosis of any other type of recurrent angioedema
- •Known family history of sudden cardiac death at a young age (< 40 years of age)
- •Creatinine clearance using the modified Schwartz formula of ≤ 30 mL/min/1.73 m^2
- •Aspartate aminotransferase or alanine aminotransferase value ≥ 3 × the upper limit of the age-appropriate normal reference range value
- •Clinically significant abnormal electrocardiogram (ECG) including but not limited to, a corrected QT interval 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
Arms & Interventions
Cohort 1: ≥ 40 kg body weight (Berotralstat 150 mg)
Participants received 150 milligram (mg) berotralstat capsule orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.
Intervention: Berotralstat (Drug)
Cohort 2: 32 to < 40 kg body weight (Berotralstat 108 mg)
Participants received 108 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.
Intervention: Berotralstat (Drug)
Cohort 3: 24 to < 32 kg body weight (Berotralstat 96 mg)
Participants received 96 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.
Intervention: Berotralstat (Drug)
Cohort 4: 12 to <24 kg body weight (Berotralstat 78 mg)
Participants received 78 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.
Intervention: Berotralstat (Drug)
Outcomes
Primary Outcomes
Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUC0-last) of Berotralstat
Time Frame: Week 2
AUC0-last is the area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration.
Area Under the Plasma Concentration-Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6) of Berotralstat
Time Frame: Predose and up to 6 hours post dose at Week 2
AUC0-6 is the area under the plasma concentration-time curve from time 0 to 6 hours.
Concentration at the End of the Dosing Interval (Ctrough) of Berotralstat
Time Frame: Predose at Week 2
Ctrough is the concentration at the end of a dosing interval of berotralstat.
Maximum Observed Plasma Concentration (Cmax) of Berotralstat
Time Frame: Predose and up to 6 hours post dose at Week 2
Cmax is the maximum observed plasma concentration of berotralstat.
Time of Last Measurable Plasma Concentration (Tlast) of Berotralstat
Time Frame: Predose and up to 6 hours post dose at Week 2
Tlast is the time of the last measurable concentration (Clast) of berotralstat collected over the sampling interval.
Time to Maximum Plasma Concentration (Tmax) of Berotralstat
Time Frame: Predose and up to 6 hours post dose at Week 2
Tmax is the time taken to reach the maximum observed plasma concentration of berotralstat.
Secondary Outcomes
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From first dose of study treatment up to approximately 73 weeks)
- Number of Adjusted Hereditary Angioedema (HAE) Attacks(Week 1 through Week 12 and Week 1 through Week 48)
- Rate of Adjusted HAE Attacks(Week 1 through Week 12 and Week 1 through Week 48)
- Duration of Adjusted HAE Attack Symptoms(Week 1 through Week 12 and Week 1 through Week 48)
- Incidence of Adjusted HAE Attack Based on Anatomical Location(Week 1 through Week 12 and Week 1 through Week 48)
- Number of Adjusted Attacks Requiring On-Demand Treatment(Week 1 through Week 12 and Week 1 through Week 48)
- Proportion of Adjusted Attacks Requiring On-Demand Treatment(Week 1 through Week 12 and Week 1 through Week 48)
- Number of Days With Angioedema Symptoms(Week 1 through Week 12 and Week 1 through Week 48)
- Proportion of Days With Angioedema Symptoms(Week 1 through Week 12 and Week 1 through Week 48)
- Assessment of Adjusted HAE Attack Severity(Week 1 through Week 12 and Week 1 through Week 48)
- Number of Participants Who Discontinued Treatment Due to Perceived Lack of Efficacy(Week 1 through Week 12 and Week 1 through Week 48)
- Number of Hospitalizations and Clinic Visits Due to HAE(Week 1 through Week 12 and Week 1 through Week 48)