Long Term Safety Study of BCX7353 in HAE

• Register: EUCTR
• Last refreshed on: 6 October 2020
• Main ID: EUCTR2017-003281-27-AT
• Date of registration: 28/11/2017
• Prospective Registration: Yes
• Primary sponsor: BioCryst Pharmaceuticals Inc
• Public title: Long Term Safety Study of BCX7353 in HAE
• Scientific title: An Open-Label study to Evaluate the Long-Term Safety of Daily Oral BCX7353 in subjects with Type I and II Hereditary Angioedema
• Date of first enrolment: 04/01/2018
• Target sample size: 475
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003281-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: yes Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Denmark, European Union, Germany, Hong Kong, Hungary, Israel, Korea, Republic of, Macedonia, the former Yugoslav Republic of, Netherlands, New Zealand, Poland, Serbia, Slovakia, South Africa, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Operations
• Affiliation: AMS Advanced Medical Services

• Name: Clinical Operations
• Affiliation: AMS Advanced Medical Services

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males and nonpregnant, nonlactating females >18 years (main study) or = 12 to 17 years of age (substudy)
2. Subjects with Type I or II HAE who either
i) have participated in a previous BCX7353 study OR
ii) In the opinion of the Investigator, are expected to benefit from treatment with an oral treatment for the prevention of angioedema attacks and have a clinical diagnosis of HAE Type I or II, defined as having a C1 esterase inhibitor (C1-INH) functional level below 50% and a complement 4 (C4) level below the lower limit of the normal (LLN) reference range, as assessed during the screening period
3. Subject weight = 40 kg
4. Access to appropriate medication for the treatment of acute HAE attacks
5. Females only: Agreement to use acceptable effective contraception
6. Able to provide written, informed consent
7. In the opinion of the Investigator, the subject is able to adequately comply with all required study procedures for the duration of the study. The subject must demonstrate adequate compliance with all study procedures required including diary recording of HAE attacks

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

Exclusion criteria:
1. Pregnancy or breast feeding or planned pregnancy during the study period
2. Any clinically significant medical condition or medical history that, in the opinion of the Investigator or Sponsor, would interfere with the subject’s safety or ability to participate in the study
3. Discontinuation of study drug due to a hypersensitivity reaction to BCX7353 in a prior study. This includes subjects who had a rash of any severity identified as possibly, probably, or definitely related to active BCX7353 in the previous study
4. Dementia, altered mental status or any psychiatric condition, that would prohibit the understanding or rendering of informed consent or participation in the study
5. Clinically significant abnormal ECG including but not limited to, a QTcF > 470 msec for women, a QTcF > 450 msec for men, a PR > 220 msec (both sexes), or ventricular and/or atrial premature contractions that are more frequent than occasional, and/or as couplets or higher in grouping
6. Unacceptable noncompliance in the previous BCX7353 efficacy study as assessed by the Sponsor or Investigator
7. Any clinically significant history of angina, myocardial infarction, syncope, clinically significant cardiac arrhythmias, left ventricular hypertrophy, cardiomyopathy, or any other cardiovascular disease
8. Known family history of sudden cardiac death. Family history of sudden death from HAE is not exclusionary
9. History of or current implanted defibrillator or pacemaker
10. Use of concomitant medications that are metabolized by CYP2D6, CYP2C9, CYP2C19, or CYP3A4 and that have a narrow therapeutic range, including those known to prolong the QT interval within 7 days of the baseline visit or planned initiation during the study
11. Use of a medication that is transported by P-gp and has a narrow therapeutic range, within 7 days of the baseline visit or planned initiation during the study
12. Any laboratory parameter abnormality that, in the opinion of the Investigator, is clinically significant and relevant for this study
13. Calculated creatinine clearance of = 30 mL/min or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value = 3 × the upper limit of the normal (ULN) reference range value at screening or last available visit prior to enrollment
14. Investigational drug exposure, other than BCX7353, within 30 days prior to the screening visit (or baseline if no screening visit)
15. Severe hypersensitivity to multiple medicinal products or severe hypersensitivity/anaphylaxis with unclear etiology
16. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse (self-reported alcoholic intake > 3 units of alcohol/day)
17. For subjects undergoing a screening visit, a positive drugs of abuse screen (unless used as a medical treatment [e.g., with a prescription])
18. For subjects undergoing a screening visit, current infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
19. Subjects with an immediate family relationship to either Sponsor employees, the Investigator or employees of the study site who are named on the delegation log
20. Subjects who are held in an institution by a government or judicial order


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Hereditary Angioedema
MedDRA version: 23.1 Level: PT Classification code 10019860 Term: Hereditary angioedema System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: BCX7353
Product Code: BCX7353
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: BCX7353
Current Sponsor code: BCX7353
Other descriptive name: BCX7353
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: BCX7353
Product Code: BCX7353
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: BCX7353
Current Sponsor code: BCX7353
Other descriptive name: BCX7353
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 110-

Product Name: BCX7353
Product Code: BCX7353
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: BCX7353
Current Sponsor code: BCX7353
Other descriptive name: BCX7353
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Main Objective: To evaluate the long-term safety and tolerability of daily dosing of oral BCX7353 in subjects with HAE

Secondary Objective: To assess the effectiveness (i.e., HAE attack frequency, severity and disease activity over time) of BCX7353 during long-term administration
To evaluate quality of life during long-term administration of BCX7353
To evaluate subject’s satisfaction with medication during long term administration of BCX7353

Timepoint(s) of evaluation of this end point: week 48
Week 96
week 240

Primary end point(s): The proportion of subjects who discontinue BCX7353 due to a treatment-emergent AE
The proportion of subjects with treatment-emergent SAEs
The proportion of subjects with treatment-emergent AEs
The proportion of subjects with treatment-emergent Grade 3 or 4 AEs
The proportion of subjects with treatment-emergent, treatment related AE consistent with a drug rash
The proportion of subjects with treatment-emergent Grade 3 or 4 laboratory abnormalities
The proportion of subjects who receive a reduced dose due to tolerability issues

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: week 48
Week 96
week 240

Secondary end point(s): Number and rate of HAE attacks
Durability of response (attack rate trend over time)
Number and proportion of days with angioedema symptoms
Patient-reported outcomes (HAE disease-specific AE-QoL questionnaire scores and TSQM Global Satisfaction scores)
Number of attacks requiring attack medication
Discontinuations due to lack of efficacy
Severity of attacks

Secondary ID(s)

NCT03472040

BCX7353-204

2017-003281-27-GB

Source(s) of Monetary Support

BioCryst Pharmaceuticals Inc

Ethics review

Status: Approved
Approval date: 13/12/2017
Contact: