Clinical trial NCT05453968: Berotralstat Treatment in Children With Hereditary Angioedema
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hereditary Angioedema
Pediatric
Keywords: berotralstat
BCX7353
Orladeyo®
once a day
Hereditary angioedema (HAE)
Pediatric
oral once a day dosing
kallikrein inhibitor
Lead sponsor: BioCryst Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-07-12
Enrollment: 29
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Pharmacokinetics: Cmax
timeFrame: Predose and multiple timepoints up to 24 hours postdose
measure: Pharmacokinetics: AUC0-tau
timeFrame: Predose and multiple timepoints up to 24 hours postdose
measure: Pharmacokinetics: CL/F
timeFrame: Predose and multiple timepoints up to 24 hours postdose
Secondary outcomes:
measure: Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Over 144 weeks
measure: Frequency and severity of hereditary angioedema (HAE) attacks
timeFrame: Over 48 weeks
Other outcomes:
measure: Acceptability/palatability of berotralstat oral granules using a self-reported taste rating scale designed with images centered on taste
timeFrame: Time of first dose (Day 1)
Locations:
city: Vienna
country: Austria
facility: Investigative Site #1
city: Ottawa
country: Canada
facility: Investigative Site #1
state: Ontario
city: Grenoble
country: France
facility: Investigative Site #3
city: Marseille
country: France
facility: Investigative Site #2
city: Paris
country: France
facility: Investigative Site #1
city: Berlin
country: Germany
facility: Investigative Site #1
city: Frankfurt
country: Germany
facility: Investigative Site #2
city: Haifa
country: Israel
facility: Investigative Site #2
city: Tel Aviv
country: Israel
facility: Investigative Site #1
city: Padova
country: Italy
facility: Investigative Site #1
city: Kraków
country: Poland
facility: Investigative Site #1
city: Sângeorgiu De Mureş
country: Romania
facility: Investigative Site #1
city: Madrid
country: Spain
facility: Investigative Site #1
city: Málaga
country: Spain
facility: Investigative Site #2
city: Bristol
country: United Kingdom
facility: Investigative Site #1
Study officials:
affiliation: Bristol Royal Hospital for Children
name: Jolanta Bernatoniene, MD
role: PRINCIPAL_INVESTIGATOR
References: