APeX-P: Berotralstat Treatment in Children With Hereditary Angioedema

Sponsor

BioCryst Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05453968

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Hereditary Angioedema Pediatric	Drug: Berotralstat	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a sequential, three-part, open-label study. Minimum participation in this study is expected to be 24 weeks in the SOC treatment period through Part 1 of the study and up to an additional 132 weeks in Parts 2 and 3.This is a sequential, three-part, open-label study. Minimum participation in this study is expected to be 24 weeks in the SOC treatment period through Part 1 of the study and up to an additional 132 weeks in Parts 2 and 3.

Masking:

None (Open Label)

Masking Description:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Berotralstat Berotralstat once daily based on 4 dose cohorts determined by participant weight. Cohorts 1 and 2 will enroll in parallel. After 4 participants from either Cohort 1 and/or 2 have completed the Week 2 visit, PK samples will be analyzed. Prior to opening Cohort 3, available PK and safety data will be reviewed by the DMC to confirm it is safe to proceed and to confirm the weight band for Cohort 3. BioCryst will notify sites when Cohort 3 is open for enrollment. A similar procedure will be followed for opening enrollment into Cohort 4.	Drug: Berotralstat Administered orally once daily at a weight-based dose in up to 4 cohorts Other Names: BCX7353 Orladeyo®

Arm

Intervention/Treatment

Experimental: Berotralstat

Berotralstat once daily based on 4 dose cohorts determined by participant weight. Cohorts 1 and 2 will enroll in parallel. After 4 participants from either Cohort 1 and/or 2 have completed the Week 2 visit, PK samples will be analyzed. Prior to opening Cohort 3, available PK and safety data will be reviewed by the DMC to confirm it is safe to proceed and to confirm the weight band for Cohort 3. BioCryst will notify sites when Cohort 3 is open for enrollment. A similar procedure will be followed for opening enrollment into Cohort 4.

Drug: Berotralstat

Administered orally once daily at a weight-based dose in up to 4 cohorts

Other Names:

BCX7353

Orladeyo®

Outcome Measures

Primary Outcome Measures

Pharmacokinetics: Cmax [Predose and multiple timepoints up to 24 hours postdose]
Maximum plasma concentration 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)
Pharmacokinetics: CL/F [Predose and multiple timepoints up to 24 hours postdose]
Apparent oral clearance of berotralstat

Secondary Outcome Measures

Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) [Over 144 weeks]
Frequency and severity of hereditary angioedema attacks (HAE) attacks [Over 48 weeks]

Other Outcome Measures

Acceptability/palatability of berotralstat oral granules using a self-reported taste rating scale designed with images centered on taste [Time of first dose (Day 1)]
TASTY; 7-point scale [0 "worst" to 6 "best"]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 11 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country
1	Investigative Site #1	Vienna		Austria
2	Investigative Site #1	Ottawa	Ontario	Canada
3	Investigative Site #2	Marseille		France
4	Investigative Site #1	Paris		France
5	Investigative Site #1	Berlin		Germany
6	Investigative Site #2	Frankfurt		Germany
7	Investigative Site #2	Haifa		Israel
8	Investigative Site #1	Tel Aviv		Israel
9	Investigative Site #1	Padova		Italy
10	Investigative Site #1	Skopje		North Macedonia
11	Investigative Site #1	Kraków		Poland
12	Investigative Site #1	Sângeorgiu De Mureş		Romania
13	Investigative Site #1	Madrid		Spain
14	Investigative Site #2	Málaga		Spain
15	Investigative Site #1	Bristol		United Kingdom
16	Investigative Site #2	London		United Kingdom