Berotralstat Treatment in Children With Hereditary Angioedema

NCT05453968 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: BCX7353-3042021-005932-50
• Study Type: interventional
• Target: 29
• Locations: 10 countries
• Sites: 15

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics (PK), safety and effectiveness of berotralstat to determine the appropriate weight-based dose for pediatric participants 2 to \< 12 years of age for prophylactic treatment to prevent attacks of hereditary angioedema (HAE).

Conditions

Hereditary Angioedema; Pediatric

Keywords

Berotralstat; BCX7353; Orladeyo; once a day; Hereditary angioedema (HAE); Pediatric; kallikrein inhibitor; Oral

Outcome Measures

Primary Outcomes (6)

• Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUC0-last) of Berotralstat

  AUC0-last is the area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration.

  Week 2

• Area Under the Plasma Concentration-Time Curve From Time 0 to 6 Hours Post-dose (AUC0-6) of Berotralstat

  AUC0-6 is the area under the plasma concentration-time curve from time 0 to 6 hours.

  Predose and up to 6 hours post dose at Week 2

• Concentration at the End of the Dosing Interval (Ctrough) of Berotralstat

  Ctrough is the concentration at the end of a dosing interval of berotralstat.

  Predose at Week 2

• Maximum Observed Plasma Concentration (Cmax) of Berotralstat

  Cmax is the maximum observed plasma concentration of berotralstat.

  Predose and up to 6 hours post dose at Week 2

• Time of Last Measurable Plasma Concentration (Tlast) of Berotralstat

  Tlast is the time of the last measurable concentration (Clast) of berotralstat collected over the sampling interval.

  Predose and up to 6 hours post dose at Week 2

• Time to Maximum Plasma Concentration (Tmax) of Berotralstat

  Tmax is the time taken to reach the maximum observed plasma concentration of berotralstat.

  Predose and up to 6 hours post dose at Week 2

Secondary Outcomes (12)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  From first dose of study treatment up to approximately 73 weeks

• Number of Adjusted Hereditary Angioedema (HAE) Attacks

  Week 1 through Week 12 and Week 1 through Week 48

• Rate of Adjusted HAE Attacks

  Week 1 through Week 12 and Week 1 through Week 48

• Duration of Adjusted HAE Attack Symptoms

  Week 1 through Week 12 and Week 1 through Week 48

• Incidence of Adjusted HAE Attack Based on Anatomical Location

  Week 1 through Week 12 and Week 1 through Week 48

Study Arms (4)

Cohort 1: ≥ 40 kg body weight (Berotralstat 150 mg)

EXPERIMENTAL

Participants received 150 milligram (mg) berotralstat capsule orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.

Drug: Berotralstat

Cohort 2: 32 to < 40 kg body weight (Berotralstat 108 mg)

EXPERIMENTAL

Participants received 108 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.

Drug: Berotralstat

Cohort 3: 24 to < 32 kg body weight (Berotralstat 96 mg)

EXPERIMENTAL

Participants received 96 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.

Drug: Berotralstat

Cohort 4: 12 to <24 kg body weight (Berotralstat 78 mg)

EXPERIMENTAL

Participants received 78 mg berotralstat granules orally once daily for up to 144 weeks. Dose modifications were permitted due to weight changes, PK results, or safety.

Drug: Berotralstat

Interventions

Berotralstat DRUG

Administered orally once daily

Also known as: BCX7353, Orladeyo®

Cohort 1: ≥ 40 kg body weight (Berotralstat 150 mg); Cohort 2: 32 to < 40 kg body weight (Berotralstat 108 mg); Cohort 3: 24 to < 32 kg body weight (Berotralstat 96 mg); Cohort 4: 12 to <24 kg body weight (Berotralstat 78 mg)

Eligibility Criteria

• Age: 2 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• For subjects who are not currently receiving prophylaxis for HAE, documented history of \>= 2 HAE attacks in the 6 months prior to the enrollment visit.

You may not qualify if:

• Concurrent diagnosis of any other type of recurrent angioedema
• Known family history of sudden cardiac death at a young age (\< 40 years of age)
• Creatinine clearance using the modified Schwartz formula of ≤ 30 mL/min/1.73 m\^2
• Aspartate aminotransferase or alanine aminotransferase value ≥ 3 × the upper limit of the age-appropriate normal reference range value
• Clinically significant abnormal electrocardiogram (ECG) including but not limited to, a corrected QT interval 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

Sponsors & Collaborators

• BioCryst Pharmaceuticals: lead

Study Sites (15)

Investigative Site #1

Vienna, Ontario, Austria

Location

Investigative Site #1

Ottawa, Ontario, Canada

Location

Investigative Site #3

Grenoble, France

Location

Investigative Site #2

Marseille, France

Location

Investigative Site #1

Paris, France

Location

Investigative Site #1

Berlin, Germany

Location

Investigative Site #2

Frankfurt, Germany

Location

Investigative Site #2

Haifa, Israel

Location

Investigative Site #1

Tel Aviv, Israel

Location

Investigative Site #1

Padua, Italy

Location

Investigative Site #1

Krakow, Poland

Location

Investigative Site #1

Sângeorgiu de Mureş, Romania

Location

Investigative Site #1

Madrid, Spain

Location

Investigative Site #2

Málaga, Spain

Location

Investigative Site #1

Bristol, United Kingdom

Location

Related Publications (1)

• 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 Dec;135(6):681-688.e3. doi: 10.1016/j.anai.2025.07.012. Epub 2025 Jul 25.

  PMID: 40716738 DERIVED

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

berotralstat

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Results Point of Contact

• Title: Study Director
• Organization: BioCryst Pharmaceuticals, Inc.

clinicaltrials@biocryst.com

+1 919-859-1302

Study Officials

• Jolanta Bernatoniene, MD

  Bristol Royal Hospital for Children

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a sequential, 3-part, open-label study. Participants were assigned a cohort based on weight at baseline.

Study Record Dates

• First Submitted: June 30, 2022
• First Posted: July 12, 2022
• Study Start: October 25, 2022
• Primary Completion: September 11, 2024
• Study Completion (Estimated): February 1, 2027
• Last Updated: February 25, 2026
• Results First Posted: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); CA (1); IT (1); GB (1); FR (3); DE (2); RO (1); ES (2); PL (1); IL (2)