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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Hereditary Angioedema; Pediatric
• Intervention / Treatment: Drug: Berotralstat

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 Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: BioCryst Pharmaceuticals, Inc.; Phone Number: 919.859.1302; Email: clinicaltrials@biocryst.com

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Berotralstat; 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.

Drug: Berotralstat; Administered orally once daily at a weight-based dose in up to 4 cohorts; Other Names: BCX7353; Orladeyo®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Cmax	Maximum plasma concentration of berotralstat	Predose and multiple timepoints up to 24 hours postdose
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
Pharmacokinetics: CL/F	Apparent oral clearance of berotralstat	Predose and multiple timepoints up to 24 hours postdose

Secondary Outcome Measures

Outcome Measure	Time Frame
Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)	Over 144 weeks
Frequency and severity of hereditary angioedema (HAE) attacks	Over 48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals
• Investigators: Principal Investigator: Jolanta Bernatoniene, MD, Bristol Royal Hospital for Children

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2022
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: June 30, 2022
• First Submitted That Met QC Criteria: July 8, 2022
• First Posted (Actual): July 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pediatric; once a day; BCX7353; kallikrein inhibitor; berotralstat; Orladeyo®; Hereditary angioedema (HAE); oral once a day dosing
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Berotralstat
• Other Study ID Numbers: BCX7353-304; 2021-005932-50 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No