A clinical trial to assess 2 different doses of BCX7353 compared to placebo as an oral treatment for the prevention of attacks in people with HAE
- Conditions
- Hereditary angioedemaMedDRA version: 20.0Level: PTClassification code 10019860Term: Hereditary angioedemaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2017-003966-29-GB
- Lead Sponsor
- BioCryst Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 121
1. Males and non-pregnant, non-lactating females = 18 years of age (main study) or = 12 to 17 years of age (substudy).
2. Able to provide written, informed consent. Subjects aged 12 to 17 years who are screening 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.
3. Subject weight of = 40 kg.
4. A clinical diagnosis of HAE Type I or Type II, defined as having a C1-INH functional level below 50% and a C4 level below the lower limit of the normal (LLN) reference range, as assessed during the Screening period. In the absence of a low C4 value drawn during the intercritical period (ie, subject is not having an HAE attack), one of the following is acceptable to confirm the diagnosis of HAE: 1) a SERPING-1 gene mutation known or likely to be associated with HAE Type I or II assessed during the screening period; 2) a confirmed family history of C1-INH deficiency; 3) a C4 redrawn and retested during an attack in the screening period with the results below the LLN reference range .
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
5. 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 (icatibant, plasma-derived C1 INH, ecallantide, or recombinant C1 INH). Cinryze used for acute treatment of HAE attacks is an acceptable medication for this purpose.
6. Subjects must be medically appropriate for on-demand treatment as the sole medicinal management for their HAE during the study.
7. The subject must have at least <> HAE attacks which meet all of the requirements during the run-in period of a maximum of 56 days from the screening visit.
8. Female and male subjects must agree to the contraception requirements (defined as acceptable effective) and must meet the inclusion criteria regarding contraception, and contraception of female partners (as applicable). Contraception is no longer required for male subjects and their female partners under protocol v3.
9. In the opinion of the Investigator, the subject is expected 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 from the screening visit through randomization, including diary recording of HAE attacks beginning at the Screening visit.
Are the trial subjects under 18? yes
Number of subjects for this age range: 6
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
1. Any clinically significant medical or psychiatric condition or medical history that, in the opinion of the Investigator or Sponsor, would interfere with the subject’s ability to participate in the study or increases the risk to the subject by participating in the study.
2. 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.
3. Anticipated use of short-term prophylaxis of angioedema attacks for a pre-planned procedure during the screening or study periods.
4. Concurrent diagnosis of any other type of recurrent angioedema.
5. Clinically significant abnormal ECG at the screening visit. This includes, but is not limited to, a QTcF > 470 msec for women, a QTcF > 450 msec for men, 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. Any clinically significant history of angina, myocardial infarction, syncope, clinically significant cardiac arrhythmias, left ventricular hypertrophy, cardiomyopathy, or any other clinically significant cardiovascular abnormality such as poorly controlled hypertension.
7. Known family history of sudden cardiac death. Family history of sudden death from HAE is not exclusionary.
8. History of or current implanted defibrillator or pacemaker.
9. Any abnormal laboratory or urinalysis parameter at screening that, in the opinion of the Investigator, is clinically significant and relevant for this study. A calculated CLcr of = 30 mL/min or AST or ALT value = 3 times the upper limit of the normal reference range value obtained during screening is exclusionary.
10. Prior enrollment in a BCX7353 study.
11. Suspected C1-INH resistance in the opinion of the Investigator or Sponsor.
12. History of alcohol or drug abuse within the previous year prior to the screening visit, or current evidence of substance dependence or abuse (self-reported alcohol intake > 3 drinks/day).
13. Positive serology for human immunodeficiency virus (HIV) or current infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
14. Pregnant, planning to become pregnant during the study, or nursing.
15. Positive drugs of abuse screen (unless drug is used as medical treatment with a prescription).
16. History of severe hypersensitivity to multiple medicinal products or severe hypersensitivity/anaphylaxis with unclear etiology.
17. Use of androgens or tranexamic acid for prophylaxis of HAE attacks within the 28 days prior to the Screening visit or initiation during the study.
18. Use of C1-INH for prophylaxis of HAE attacks within the 14 days prior to the Screening visit or initiation during the study. Use of a C1-INH therapy for treatment of attacks is not excluded at any time, nor is C1-INH for preprocedure prophylaxis for an unplanned/unforeseen procedure.
19. Use of concomitant medications that are metabolized by CYP2D6, CYP2C9, CYP2C19, and CYP3A4 and have a narrow therapeutic range, within 7 days of the baseline visit or planned initiation during the study.
20. Use of a medication that is clinically known to prolong the QT interval and is metabolized by CYP2D6, CYP2C9, CYP2C19, and/or CYP3A4 7 days prior to the baseline visit or planned initiation during the study.
21. Use of a medication that is transported by P-gp and has a narrow therapeutic range,
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method