Back to resultsBerotralstat Treatment in Children With Hereditary Angioedema (APeX-P)
Primary Purpose
Hereditary Angioedema, Pediatric
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Berotralstat
Sponsored by
About this trial
This is an interventional treatment trial for Hereditary Angioedema focused on measuring berotralstat, BCX7353, Orladeyo®, once a day, Hereditary angioedema (HAE), Pediatric, oral once a day dosing, kallikrein inhibitor
Eligibility Criteria
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
Sites / Locations
- Investigative Site #1Recruiting
- Investigative Site #1Recruiting
- Investigative Site #3
- Investigative Site #2Recruiting
- Investigative Site #1Recruiting
- Investigative Site #1
- Investigative Site #2Recruiting
- Investigative Site #2Recruiting
- Investigative Site #1Recruiting
- Investigative Site #1Recruiting
- Investigative Site #1
- Investigative Site #1Recruiting
- Investigative Site #1Recruiting
- Investigative Site #2Recruiting
- Investigative Site #1Recruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Berotralstat
Arm 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.
Outcomes
Primary Outcome Measures
Pharmacokinetics: Cmax
Maximum plasma concentration of berotralstat
Pharmacokinetics: AUC0-tau
Area under the plasma concentration berotralstat time curve from time zero to the end of dosing (tau)
Pharmacokinetics: CL/F
Apparent oral clearance of berotralstat
Secondary Outcome Measures
Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)
Frequency and severity of hereditary angioedema attacks (HAE) attacks
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05453968
Brief Title
Berotralstat Treatment in Children With Hereditary Angioedema
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 25, 2022 (Actual)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
July 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioCryst Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema, Pediatric
Keywords
berotralstat, BCX7353, Orladeyo®, once a day, Hereditary angioedema (HAE), Pediatric, oral once a day dosing, kallikrein inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Masking Description
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Berotralstat
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Berotralstat
Other Intervention Name(s)
BCX7353, Orladeyo®
Intervention Description
Administered orally once daily at a weight-based dose in up to 4 cohorts
Primary Outcome Measure Information:
Title
Pharmacokinetics: Cmax
Description
Maximum plasma concentration of berotralstat
Time Frame
Predose and multiple timepoints up to 24 hours postdose
Title
Pharmacokinetics: AUC0-tau
Description
Area under the plasma concentration berotralstat time curve from time zero to the end of dosing (tau)
Time Frame
Predose and multiple timepoints up to 24 hours postdose
Title
Pharmacokinetics: CL/F
Description
Apparent oral clearance of berotralstat
Time Frame
Predose and multiple timepoints up to 24 hours postdose
Secondary Outcome Measure Information:
Title
Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)
Time Frame
Over 144 weeks
Title
Frequency and severity of hereditary angioedema attacks (HAE) attacks
Time Frame
Over 48 weeks
Other Pre-specified Outcome Measures:
Title
Acceptability/palatability of berotralstat oral granules using a self-reported taste rating scale designed with images centered on taste
Description
TASTY; 7-point scale [0 "worst" to 6 "best"]
Time Frame
Time of first dose (Day 1)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
11 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
BioCryst Pharmaceuticals, Inc.
Phone
919.859.1302
Email
clinicaltrials@biocryst.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Buckland, MBBS, PhD, FRCP
Organizational Affiliation
Great Ormond St Hospital for Children NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Investigative Site #1
City
Vienna
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #1
City
Ottawa
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #3
City
Grenoble
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc
Facility Name
Investigative Site #2
City
Marseille
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #1
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #1
City
Berlin
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #2
City
Frankfurt
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #2
City
Haifa
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #1
City
Tel Aviv
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #1
City
Padova
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #1
City
Kraków
Country
Poland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #1
City
Sângeorgiu De Mureş
Country
Romania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #1
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #2
City
Málaga
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
Facility Name
Investigative Site #1
City
Bristol
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BioCryst Pharmaceuticals, Inc.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Berotralstat Treatment in Children With Hereditary Angioedema
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