Hereditary Angioedema MedDRA version: 20.0 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 2. Subjects with Type I or II HAE who have participated in a BCX7353 efficacy study 3. Access to appropriate medication for the treatment of acute HAE attacks 4. Female participants must meet at least 1 of the following requirements: a. Be a woman of childbearing potential (defined as a nonmenopausal female who has not had a hysterectomy, bilateral oophorectomy, or documented ovarian failure) who agrees to use at least an acceptable effective contraceptive method during the study and for a duration of 30 days after last dose of study drug. Female subjects who report being postmenopausal for = 2 years and have a follicle stimulating hormone (FSH) = 40 mIU/mL must agree to use at least an acceptable effective contraceptive method and (as proposed above) during study and for 30 days after the last dose of study drug. b. Be a woman of non-childbearing potential (defined as postmenopausal for > 2 years or having an FSH > 40 mIU/mL if postmenopausal = 2 years or have had a hysterectomy, bilateral oophorectomy, or documented ovarian failure. Non-childbearing potential may also be demonstrated in the previous efficacy study). c. Be a woman declaring herself as either sexually abstinent or exclusively having female sexual partners. Abstinence in this study is defined as "true abstinence: when this is in line with the preferred and usual lifestyle of the subject." 5. Male subjects must comply with the following requirements through the end of the study: a. Subjects with female partners of childbearing potential (defined as postmenopausal = 2 years or a nonmenopausal female who has not had a hysterectomy, bilateral oophorectomy, or documented ovarian failure) must agree to utilize at least 1 acceptably effective contraceptive method. b. Male subjects who declare themselves as sexually abstinent are acceptable for the purposes of this study. Abstinence in this study is defined as “true abstinence: when this is in line with the preferred and usual lifestyle of the subject.” 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 65 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
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 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 have a narrow therapeutic range, within 7 days of the baseline visit or planned initiation during the study, including those known to prolong the QT interval 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 = 60 mL/min or AST or ALT value = 2 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. History of severe hypersensitivity to any medicinal product, which was associated with non HAE-related swelling, a severe rash requiring treatment/hospitalization, or anaphylaxis 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 |
|---|---|
| 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;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;Timepoint(s) of evaluation of this end point: week 48 | — |
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 | — |
Countries
Australia, Austria, Belgium, Denmark, Germany, Hungary, Italy, Macedonia, the former Yugoslav Republic of, Netherlands, Poland, Slovakia, Spain, Switzerland, United Kingdom
Contacts
Public ContactClinical Operations
AMS Advanced Medical Services
Outcome results
None listed