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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05453968
Recruitment Status : Active, not recruiting
First Posted : July 12, 2022
Last Update Posted : March 13, 2024
Sponsor:
Information provided by (Responsible Party):
BioCryst Pharmaceuticals

Study Description
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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).

Condition or disease Intervention/treatment Phase
Hereditary Angioedema Pediatric Drug: Berotralstat Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Masking Description: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 25, 2022
Estimated Primary Completion Date : July 2025
Estimated Study Completion Date : July 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
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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®


Outcome Measures
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Primary Outcome Measures :
  1. Pharmacokinetics: Cmax [ Time Frame: Predose and multiple timepoints up to 24 hours postdose ]
    Maximum plasma concentration of berotralstat

  2. Pharmacokinetics: AUC0-tau [ Time Frame: Predose and multiple timepoints up to 24 hours postdose ]
    Area under the plasma concentration berotralstat time curve from time zero to the end of dosing (tau)

  3. Pharmacokinetics: CL/F [ Time Frame: Predose and multiple timepoints up to 24 hours postdose ]
    Apparent oral clearance of berotralstat


Secondary Outcome Measures :
  1. Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Over 144 weeks ]
  2. Frequency and severity of hereditary angioedema (HAE) attacks [ Time Frame: Over 48 weeks ]

Other Outcome Measures:
  1. Acceptability/palatability of berotralstat oral granules using a self-reported taste rating scale designed with images centered on taste [ Time Frame: Time of first dose (Day 1) ]
    TASTY; 7-point scale [0 "worst" to 6 "best"]


Eligibility Criteria
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Ages Eligible for Study:   2 Years to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05453968


Locations
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Austria
Investigative Site #1
Vienna, Austria
Canada, Ontario
Investigative Site #1
Ottawa, Ontario, Canada
France
Investigative Site #3
Grenoble, France
Investigative Site #2
Marseille, France
Investigative Site #1
Paris, France
Germany
Investigative Site #1
Berlin, Germany
Investigative Site #2
Frankfurt, Germany
Israel
Investigative Site #2
Haifa, Israel
Investigative Site #1
Tel Aviv, Israel
Italy
Investigative Site #1
Padova, Italy
Poland
Investigative Site #1
Kraków, Poland
Romania
Investigative Site #1
Sângeorgiu De Mureş, Romania
Spain
Investigative Site #1
Madrid, Spain
Investigative Site #2
Málaga, Spain
United Kingdom
Investigative Site #1
Bristol, United Kingdom
Sponsors and Collaborators
BioCryst Pharmaceuticals
Investigators
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Principal Investigator: Jolanta Bernatoniene, MD Bristol Royal Hospital for Children
More Information
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Responsible Party: BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05453968    
Other Study ID Numbers: BCX7353-304
2021-005932-50 ( EudraCT Number )
First Posted: July 12, 2022    Key Record Dates
Last Update Posted: March 13, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioCryst Pharmaceuticals:
berotralstat
BCX7353
Orladeyo®
once a day
 Hereditary angioedema (HAE)
Pediatric
oral once a day dosing
kallikrein inhibitor
Additional relevant MeSH terms:
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Angioedema
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
 Hereditary Complement Deficiency Diseases
Primary Immunodeficiency Diseases
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Berotralstat
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action