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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05453968
Recruitment Status : Recruiting
First Posted : July 12, 2022
Last Update Posted : November 7, 2023
Information provided by (Responsible Party):
BioCryst Pharmaceuticals

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 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

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®

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"]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   2 Years to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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 identifier (NCT number): NCT05453968

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Contact: BioCryst Pharmaceuticals, Inc. 919.859.1302

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Investigative Site #1 Recruiting
Vienna, Austria
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Canada, Ontario
Investigative Site #1 Recruiting
Ottawa, Ontario, Canada
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Investigative Site #3 Recruiting
Grenoble, France
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Investigative Site #2 Recruiting
Marseille, France
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Investigative Site #1 Recruiting
Paris, France
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Investigative Site #1 Recruiting
Berlin, Germany
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Investigative Site #2 Recruiting
Frankfurt, Germany
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Investigative Site #2 Recruiting
Haifa, Israel
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Investigative Site #1 Recruiting
Tel Aviv, Israel
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Investigative Site #1 Recruiting
Padova, Italy
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Investigative Site #1 Recruiting
Kraków, Poland
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Investigative Site #1 Recruiting
Sângeorgiu De Mureş, Romania
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Investigative Site #1 Recruiting
Madrid, Spain
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Investigative Site #2 Recruiting
Málaga, Spain
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United Kingdom
Investigative Site #1 Recruiting
Bristol, United Kingdom
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Sponsors and Collaborators
BioCryst Pharmaceuticals
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Principal Investigator: Jolanta Bernatoniene, MD Bristol Royal Hospital for Children
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Responsible Party: BioCryst Pharmaceuticals Identifier: NCT05453968    
Other Study ID Numbers: BCX7353-304
2021-005932-50 ( EudraCT Number )
First Posted: July 12, 2022    Key Record Dates
Last Update Posted: November 7, 2023
Last Verified: November 2023
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:
once a day
Hereditary angioedema (HAE)
oral once a day dosing
kallikrein inhibitor
Additional relevant MeSH terms:
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Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Immune System Diseases
Hereditary Complement Deficiency Diseases
Primary Immunodeficiency Diseases
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action