Berotralstat Treatment in Children With Hereditary Angioedema

Pediatric Clinical Trial

— APeX-P  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05453968
• Other study ID #: BCX7353-304
• Secondary ID: 2021-005932-50
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 25, 2022
• Est. completion date: July 2027

Study information

• Verified date: March 2024
• Source: BioCryst Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 29
• Est. completion date: July 2027
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 11 Years

Eligibility

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

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema
• Pediatric

Intervention

Drug:
• Berotralstat
Administered orally once daily at a weight-based dose in up to 4 cohorts

Locations

Country	Name	City	State
Austria	Investigative Site #1	Vienna
Canada	Investigative Site #1	Ottawa	Ontario
France	Investigative Site #3	Grenoble
France	Investigative Site #2	Marseille
France	Investigative Site #1	Paris
Germany	Investigative Site #1	Berlin
Germany	Investigative Site #2	Frankfurt
Israel	Investigative Site #2	Haifa
Israel	Investigative Site #1	Tel Aviv
Italy	Investigative Site #1	Padova
Poland	Investigative Site #1	Kraków
Romania	Investigative Site #1	Sângeorgiu De Mures
Spain	Investigative Site #1	Madrid
Spain	Investigative Site #2	Málaga
United Kingdom	Investigative Site #1	Bristol

Sponsors (1)

Lead Sponsor	Collaborator
BioCryst Pharmaceuticals

Countries where clinical trial is conducted

Austria,  Canada,  France,  Germany,  Israel,  Italy,  Poland,  Romania,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Acceptability/palatability of berotralstat oral granules using a self-reported taste rating scale designed with images centered on taste	TASTY; 7-point scale [0 "worst" to 6 "best"]	Time of first dose (Day 1)
Primary	Pharmacokinetics: Cmax	Maximum plasma concentration of berotralstat	Predose and multiple timepoints up to 24 hours postdose
Primary	Pharmacokinetics: AUC0-tau	Area under the plasma concentration berotralstat time curve from time zero to the end of dosing (tau)	Predose and multiple timepoints up to 24 hours postdose
Primary	Pharmacokinetics: CL/F	Apparent oral clearance of berotralstat	Predose and multiple timepoints up to 24 hours postdose
Secondary	Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)		Over 144 weeks
Secondary	Frequency and severity of hereditary angioedema (HAE) attacks		Over 48 weeks