BEROTRALSTAT for Hereditary angioedema

Inclusion criteria

• {"criterion_text":"- Male and non-pregnant, non-lactating females 2 to < 12 years of age and weighing ≥ 12 kg.\n- Parent/caregiver willing and able to provide written, informed consent (with assent from the child where appropriate).\n- 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.\n- 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.\n- 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.\n- In the opinion of the investigator, the subject would benefit from long-term oral prophylaxis.\n- 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

• {"criterion_text":"- Concurrent diagnosis of any other type of recurrent angioedema.\n- 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.\n- 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.\n- Any result at screening that, in the opinion of the investigator, is clinically significant and relevant for this study.\n- Known hypersensitivity to berotralstat or any of its formulation excipients\n- 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.\n- 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.\n- History of or current implanted defibrillator or pacemaker.\n- Moderate to severe hepatic impairment (Child-Pugh B or C).\n- 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.\n- History of severe hypersensitivity to multiple medicinal products or severe hypersensitivity/anaphylaxis with unclear etiology.\n- 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.]\n- An immediate family relationship to either sponsor employees, the investigator, or employees of the study site named on the delegation log."}

Primary endpoints

• {"endpoint_text":"- PK : The primary endpoint is the characterization of the PK profile of berotralstat in subjects aged 2 to < 12 years.","definition_or_measurement_approach":"Characterization of pharmacokinetic (PK) parameters of berotralstat administered orally to pediatric subjects aged 2 to <12 years (description of PK parameters and sampling as per protocol)."}

Secondary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Assessment by recording frequency and severity of AEs/SAEs, laboratory tests (clinical chemistry, hematology, coagulation), vital signs, ECGs, growth measures and physical exam findings as collected per protocol schedule."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Effectiveness measured by counts and characteristics of HAE attacks (frequency, duration, location), use of on-demand treatments, days with symptoms, severity assessments, discontinuations for lack of efficacy, and healthcare utilization reported from Week 1 through Weeks 12 and 48."}

Austria

Earliest CTIS Part Ii Submission Date

29-09-2024

Latest Decision Or Authorization Date

07-03-2025

Processing Time Days

159

Number Of Sites

1

Number Of Participants

3

Italy

Earliest CTIS Part Ii Submission Date

30-09-2024

Latest Decision Or Authorization Date

10-03-2025

Processing Time Days

161

Number Of Sites

1

Number Of Participants

4

Poland

Earliest CTIS Part Ii Submission Date

25-09-2024

Latest Decision Or Authorization Date

09-04-2025

Processing Time Days

196

Number Of Sites

1

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

06-03-2025

Processing Time Days

167

Number Of Sites

1

Number Of Participants

3

France

Earliest CTIS Part Ii Submission Date

08-10-2024

Latest Decision Or Authorization Date

04-03-2025

Processing Time Days

147

Number Of Sites

3

Number Of Participants

3

Germany

Earliest CTIS Part Ii Submission Date

25-09-2024

Latest Decision Or Authorization Date

06-03-2025

Processing Time Days

162

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Biocryst Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Syneos Health Netherlands B.V.

Responsibilities

Sponsor duties codes: 1, 11, 12, 7 (as provided)

Name

Pharpoint Research Inc.

Responsibilities

Sponsor duties codes: 10, 6 (as provided)

Name

Drug Development Solutions Limited

Responsibilities

PK Testing

Name

PPD Global Central Labs

Responsibilities

Clinical chemistry, Clinical haematology, Urinalysis, pregnancy Test

Third parties

• {"country":"France","full_name":"Novasco","duties_or_roles":"Patient Travel Cost Reimbursement (optional vendor)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"Investigational Materials; code 3 (no text provided)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"Sponsor duties codes: 1, 11, 12, 7 (as provided)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharpoint Research Inc.","duties_or_roles":"Sponsor duties codes: 10, 6 (as provided)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Drug Development Solutions Limited","duties_or_roles":"PK Testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"National Jewish Health","duties_or_roles":"Genetic testing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"The Andwin Corp.","duties_or_roles":"Clinical Trial Supply Management (Ancillary Supplies and Equipment)","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Clinical chemistry Clinical haematology Urinalysis, pregnancy Test; code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Illingworth Research Group Limited","duties_or_roles":"Patient Travel Arrangements and Travel Cost Reimbursement (optional vendor)","organisation_type":"Hospital/Clinic/Other health care facility"}