Berotralstat Treatment in Children With Hereditary Angioedema

NCT ID: NCT05453968

Last Updated: 2025-09-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-25
• Study Completion Date: 2027-02-28

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.

Conditions

Hereditary Angioedema; Pediatric

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Berotralstat

Intervention Type: DRUG

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

Interventions

Berotralstat

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

Intervention Type: DRUG

Other Intervention Names

BCX7353; Orladeyo®

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioCryst Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jolanta Bernatoniene, MD

Role: PRINCIPAL_INVESTIGATOR

Bristol Royal Hospital for Children

Locations

Investigative Site #1

Vienna, , Austria

Investigative Site #1

Ottawa, Ontario, Canada

Investigative Site #3

Grenoble, , France

Investigative Site #2

Marseille, , France

Investigative Site #1

Paris, , France

Investigative Site #1

Berlin, , Germany

Investigative Site #2

Frankfurt, , Germany

Investigative Site #2

Haifa, , Israel

Investigative Site #1

Tel Aviv, , Israel

Investigative Site #1

Padua, , Italy

Investigative Site #1

Krakow, , Poland

Investigative Site #1

Sângeorgiu de Mureş, , Romania

Investigative Site #1

Madrid, , Spain

Investigative Site #2

Málaga, , Spain

Investigative Site #1

Bristol, , United Kingdom

Countries

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

References

Bernatoniene J, Bourgoin-Heck M, Cancian M, Yang W, Hagin D, Pagnier A, Stobiecki M, Kinaciyan T, Phillips-Angles E, Gayet S, Bara NA, Hunter J, Mateescu E, DeSpirito M, Johnston D, Long D, Iocca H, Petroni D, Aygoren-Pursun E. Oral berotralstat for hereditary angioedema prophylaxis in patients aged 2 to <12 years: APeX-P interim results. Ann Allergy Asthma Immunol. 2025 Jul 25:S1081-1206(25)00352-7. doi: 10.1016/j.anai.2025.07.012. Online ahead of print.

Reference Type: DERIVED

PMID: 40716738 (View on PubMed)

Other Identifiers

2021-005932-50

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BCX7353-304

Identifier Type: -

Identifier Source: org_study_id