Hereditary Angioedema MedDRA version: 17.1 Level: PT Classification code 10019860 Term: Hereditary angioedema System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: BCX4161
Product Code: BCX4161
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: BCX4161
Current Sponsor code: BCX4161
Other descriptive name: BCX4161
Concentration unit: mg milligr
Sponsors
BioCryst Pharmaceuticals Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and non-pregnant, non-lactating females age =18 years. 2. Body mass index (BMI) of 19-36 kg/m2. 3. A clinical diagnosis of hereditary angioedema Type 1 or Type 2 as documented by: a. A low C1 INH antigenic level OR b. A normal C1 INH antigenic level and a low C1 INH functional level 4. Female participants must meet one of the following requirements: • A woman of childbearing potential (defined as a non-menopausal female who has not had a hysterectomy, bilateral oophorectomy, or documented ovarian failure) who agrees to use a highly effective method of contraception for the study duration and for 30 days after study drug dosing. Female subjects who report being postmenopausal for = 2 years and have a screening follicle stimulating hormone (FSH) = 40 mIU/mL must agree to use a highly effective contraceptive method • A woman of non-childbearing potential (defined as being postmenopausal for > 2 years, having a screening FSH > 40 mIU/mL if postmenopausal for = 2 years, or a woman who has had a hysterectomy, bilateral oophorectomy, or documented ovarian failure). • A woman declaring herself as either sexually abstinent or exclusively having female sexual partners. 5. Male participants must comply with the following requirements: • Must agree to utilize one highly effective contraceptive method 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) through Week 12 and for 90 days after the last dose of study drug. • Must abstain from sperm donation through Week 12 and for 90 days after the last dose of study drug. 6. Any concomitant medication at screening must be anticipated to be continued through the entire study and be of a stable dose and regimen for the duration of the entire study, including oral androgens prescribed for the prevention of HAE attacks. 7. 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. Cinryze used for acute treatment of HAE attacks is an acceptable medication for this purpose. 8. Written informed consent. 9. A documented HAE attack rate established by one of the following criteria: a. Previous documentation of pre-determined HAE attacks per month for 3 consecutive months (93 days) within the 6 months prior to screening. For subjects who have received effective prophylaxis, there must be documentation of a pre-determined attack rate per month for 3 consecutive months (93 days) within the 12 months prior to screening. A documented attack rate cannot be used for subjects who have received effective prophylaxis for more than 9 months immediately prior to screening. b. A subject diary record of unique HAE attacks collected in a run-in period of a maximum of 2 months (62 days). 10. In the opinion of the Investigator, the subject is expected to adequately comply with all required study procedures for the duration of the study. 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 84 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: 1. Females who are pregnant (positive urine or serum pregnancy test) or breast feeding at the screening visit or who are planning to become pregnant during the study. 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. For example, subjects with chronic renal failure, decompensated liver disease, or chronic heart failure would not be eligible under this criterion. 3. Dementia, altered mental status or any psychiatric condition, or stay in an institution further to an official or court order that would prohibit the understanding or rendering of informed consent or participation in the study. 4. Use of an estrogen- and/or progestin-containing hormonal contraceptive within 60 days prior of the screening visit; or expected initiation at any time through the end of the study (follow up). IUDs containing progestin can be placed at any time prior to the screening visit. 5. Use within the 7 days prior to the screening visit or expected use at any time through the end of the study of C1 INH or tranexamic acid for prophylaxis of HAE attacks. Use of a C1INH therapy for treatment of acute attacks is not excluded. 6. Use within the 30 days prior to the screening visit or expected use at any time through the end of the study of androgens for prophylaxis of HAE attacks, except for subjects who meet the required attack frequency inclusion criterion while currently being treated with androgens for prophylaxis. Such subjects must have been on a stable dose of androgens for the 90 days prior to the screening visit and agree to remain on their current dose of androgens for the duration of the study. 7. Prior enrollment in OPuS-1. 8. INR > 1.3 x ULN. 9. Creatinine clearance (CLcr) less than 60 mL/min. 10. Concurrent use of angiotensin converting enzyme inhibitors from the screening visit or expected use at any time through the end of the study. 11. Current or past medical history of acute pancreatitis, chronic pancreatitis, or pancreatic insufficiency. 12. Clinically significant abnormal ECG as assessed by the Investigator. 13. Any abnormal laboratory or urinalysis finding at the screening visit that, in the opinion of the Investigator or Sponsor, is clinically significant and relevant for this study. 14. Current participation in any other investigational drug study or within 30 days prior to the screening visit. 15. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse (self-reported alcoholic intake > 3 units alcohol/day). 16. Positive drugs of abuse screen (unless as used as medical treatment, e.g., with a prescription). 17. Positive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of prophylactic BCX4161 300 mg and 500 mg administered three times daily for 12 weeks compared to placebo;Secondary Objective: To assess the safety and tolerability of BCX4161 at 300 mg and 500 mg administered three times daily for 12 weeks To assess effects of BCX4161 on HAE disease activity and HAE attack characteristics To evaluate the effects of BCX4161 on quality of life To describe the pharmacokinetics of BCX4161 To characterize the pharmacodynamic effects of BCX4161 ;Primary end point(s): The mean acute angioedema attack rate in each active treatment group and placebo;Timepoint(s) of evaluation of this end point: End of Treatment - 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Number of attack-free days • Number of subjects who are attack-free • Disease activity, as measured by the AAS84 (AAS over 84 days) • Quality of Life, as measured by the AE-QoL and EQ-5D-5L • Acute HAE attack medication administrations • Discontinuations due to lack of efficacy ;Timepoint(s) of evaluation of this end point: End of Treatment - 12 weeks | — |
Countries
Belgium, France, Germany, Hungary, Italy, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Operations
AMS Advanced Medical Services Ltd
Outcome results
None listed