Berotralstat Treatment in Children With Hereditary Angioedema (APeX-P)

BioCryst

Status and phase: Active, not recruiting; Phase 3

Conditions: Pediatric; Hereditary Angioedema

Treatments: Drug: Berotralstat

Study type: Interventional

Funder types: Industry

Identifiers

NCT05453968

BCX7353-304

2021-005932-50 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 29 patients

Sex: All

Ages: 2 to 11 years old

Volunteers: No Healthy Volunteers

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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

Berotralstat

Experimental group

Description:

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.

Treatment:

Drug: Berotralstat