A safety and pharmacokinetic study of oral berotralstat for HAE attacks in pediatric patients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biocryst Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

13 Oct 2022 → ongoing

Decision date (initial)

2024-09-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

BioCryst Pharmaceuticals, Inc.

External identifiers

EU CT number

2024-511257-22-00

EudraCT number

2021-005932-50

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Safety

To describe the pharmacokinetic (PK) parameters of berotralstat administered orally to pediatric subjects with HAE aged 2 to < 12 years old and weighing ≥ 12 kg.

Secondary objectives 2

1. • To assess the safety and tolerability of berotralstat administered orally to pediatric subjects with HAE aged 2 to < 12 years old and weighing ≥ 12 kg.
2. • To summarize the effectiveness of berotralstat in pediatric subjects with HAE aged 2 to < 12 years old and weighing ≥ 12 kg.

Conditions and MedDRA coding

Hereditary Angioedema (HAE)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-022449-PIP02-18

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male and non-pregnant, non-lactating females 2 to < 12 years of age and weighing ≥ 12 kg.
2. Parent/caregiver willing and able to provide written, informed consent (with assent from the child where appropriate).
3. Subjects with a clinical diagnosis of HAE. A clinical diagnosis of HAE is defined as: a. Screening results that document immunogenic C1-INH antigenic level below the lower limit of normal (LLN) reference range or C1-INH function < 50% and a complement 4 (C4) level below LLN reference range. OR b. Laboratory documentation of historical C1-INH functional level below the assay lower limit of normal OR c. For subjects with C1-INH function ≥ 50% but less than the assay LLN, a SERPING-1 gene mutation known or likely to be associated with HAE Type I or II, as assessed during the screening period OR a repeat C1-INH functional level < 50% will be considered acceptable for enrollment. OR d. Historical or new laboratory documentation of a SERPING-1 mutation known or likely to be associated with HAE OR e. For subjects who currently use plasma-derived or recombinant C1-INH-based prophylactic therapies, a confirmed family history of C1-INH deficiency.
4. 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.
5. Access to and ability to use one or more acute medications approved by the relevant competent authority for the treatment of acute attacks of HAE.
6. In the opinion of the investigator, the subject would benefit from long-term oral prophylaxis.
7. Females who had started their menses and males must be either: Sexually abstinent (Section 9.2.1.1 of the protocol ); OR b. If sexually active , or become sexually active during the study, must agree to the use of effective contraception (Section 9.2.1.1 of the protocol)

Exclusion criteria 13

1. Concurrent diagnosis of any other type of recurrent angioedema.
2. Any clinically significant history of angina, myocardial infarction, syncope, clinically significant cardiac arrhythmias, left ventricular hypertrophy, cardiomyopathy, myocarditis, pericarditis, congenital heart defects, or any other clinically significant cardiovascular abnormality such as poorly controlled hypertension.
3. Known family history of sudden cardiac death at a young age (ie, < 40 years of age). Family history of sudden death from HAE is not exclusionary.
4. History of or current implanted defibrillator or pacemaker.
5. Moderate to severe hepatic impairment (Child-Pugh B or C).
6. A calculated creatinine clearance using the Modified Schwartz formula of ≤ 30 mL/min/1.73 m2 or aspartate aminotransferase or alanine aminotransferase value ≥ 3 × the upper limit of the age-appropriate normal reference range value.
7. History of severe hypersensitivity to multiple medicinal products or severe hypersensitivity/anaphylaxis with unclear etiology.
8. Current participation in any other investigational drug study or received another investigational drug within 30 days of enrollment; not willing to refrain from participation in another clinical study after enrollment and for the duration of the study. [Note: drugs/vaccines approved under FDA emergency use authorization (or country-specific analogous regulations) are not considered excluded or prohibited under this criterion.]
9. An immediate family relationship to either sponsor employees, the investigator, or employees of the study site named on the delegation log.
10. Any clinically significant medical condition or medical history (including altered mental status) that, in the opinion of the investigator or sponsor, would interfere with the subject's safety or ability to participate in the study. Examples include but are not limited to active malignancy under treatment, uncontrolled cardiovascular disease, organ dysfunction requiring supportive care.
11. Clinically significant abnormal ECG including but not limited to, a corrected QT interval calculated using Fridericia's correction (QTcF = QT/RR0.33) > 450 msec, or ventricular and/or atrial premature contractions that are more frequent than occasional, and/or as couplets or higher in grouping.
12. Any result at screening that, in the opinion of the investigator, is clinically significant and relevant for this study.
13. Known hypersensitivity to berotralstat or any of its formulation excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PK : The primary endpoint is the characterization of the PK profile of berotralstat in subjects aged 2 to < 12 years.

Secondary endpoints 2

1. Safety : The frequency and severity of adverse events (AEs) and serious adverse events (SAEs), laboratory analyses (clinical chemistry, hematology, coagulation), height, weight, vital signs, electrocardiograms (ECGs), and physical examination findings
2. Effectiveness: The frequency of attacks, duration of symptoms, anatomical location of attack, on-demand treatment, number of days with angioedema symptoms, assessment of attack severity, discontinuations due to lack of efficacy, and number of hospitalizations and clinic visits from Week 1 through Weeks 12 and 48

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biocryst Pharmaceuticals Inc.

Sponsor organisation

Biocryst Pharmaceuticals Inc.

Address

4505 Emperor Boulevard Suite 200

City

Durham

Postcode

27703-8457

Country

United States

Scientific contact point

Organisation

Biocryst Pharmaceuticals Inc.

Contact name

Biocryst Pharmaceuticals Inc.

Public contact point

Organisation

Biocryst Pharmaceuticals Inc.

Contact name

Biocryst Pharmaceuticals Inc.

Third parties 9

Locations

6 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 44 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications