Hereditary Angioedema MedDRA version: 23.1 Level: PT Classification code 10019860 Term: Hereditary angioedema System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
BioCryst Pharmaceuticals Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and nonpregnant, nonlactating females =18 years of age (main study) or =12 to 17 years of age (substudy) 2. Subjects with Type I or II HAE who have participated in a BCX7353 efficacy study OR expected to derive benefit from oral treatment for the prevention of angioedema attacks and have a clinical diagnosis of HAE Type 1 or Type2, defined as C1-INH functional level below 50% and C4 level below lower limit of normal OR a known SERPING-1 gene mutation known or likely to be associated with HAE Type 1 or 2 OR confirmed family history OR low C4 value from a sample drawn during a HAE attack. 3. Subject weight = 40kg 4. Access to appropriate medication for the treatment of acute HAE attacks 5. Female subjects only: Use of acceptable effective contraception 7. Able to provide written, informed consent. Sub-study subjects aged =12 to 17 years who are screened for the substudy must be able to read, understand, and be willing to sign an assent form in addition to a caregiver providing informed consent 8. 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? yes Number of subjects for this age range: 10 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
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 a previous BCX7353 study (if applicable) 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 (CLcr) of = 30 mL/min or AST or ALT value = 3 times the ULN reference range value at screening or at the 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 ;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;Main Objective: To evaluate the long-term safety and tolerability of daily dosing of oral BCX7353 in subjects with HAE;Timepoint(s) of evaluation of this end point: week 48 Week 96 week 240 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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;Timepoint(s) of evaluation of this end point: week 48 Week 96 week 240 | — |
Countries
Australia, Austria, Belgium, Denmark, European Union, Germany, Hong Kong, Hungary, Israel, Italy, Korea, Republic of, Macedonia, the former Yugoslav Republic of, Netherlands, New Zealand, Poland, Serbia, Slovakia, South Africa, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Operations
AMS Advanced Medical Services
Outcome results
None listed