BCX7353 for the prevention of HAE attacks

• Register: EUCTR
• Last refreshed on: 9 October 2017
• Main ID: EUCTR2016-001272-29-AT
• Date of registration: 21/07/2016
• Prospective Registration: Yes
• Primary sponsor: BioCryst Pharmaceuticals Inc
• Public title: BCX7353 for the prevention of HAE attacks
• Scientific title: A randomized, double-blind, placebo-controlled, dose-ranging, parallel-group study to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of BCX7353 as a preventative treatment to reduce the frequency of attacks in subjects with hereditary angioedema
• Date of first enrolment: 30/09/2016
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001272-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 6
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Canada, Denmark, European Union, Germany, Greece, Hungary, Macedonia, the former Yugoslav Republic of, Spain, Switzerland, United Kingdom

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
1 Able to provide written, informed consent
2 Males and non-pregnant, non-lactating females age 18 to 70 years
3 A clinical diagnosis of hereditary angioedema Type 1 or Type 2 as
documented at any time in the medical records or at the screening visit
by a low C1 INH functional level (Type 2) or a low C1 INH antigenic level
(Type 1)
4 A documented HAE attack rate of <> HAE attacks per
month for <> within the 6 months prior to the screening
visit as documented in acceptable source records.
5 Access to and ability to use 1 or more acute medications approved by
the relevant competent authority for the treatment of attacks of HAE
(icatibant, plasma-derived C1 INH or recombinant C1 INH).
6 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. One or more of the following methods
are acceptable:
- surgical sterilization (ie, bilateral tubal occlusion or vasectomy of male
partner)
- placement of an intrauterine device (IUD) or intrauterine system (IUS)
(implanted any time prior to or during screening)
- progesterone-only (implantable or injectable only) hormonal
contraception associated with inhibition of ovulation initiated at least 60
days prior to the screening visit
- male or female condom with or without spermicide
- occlusive cap with spermicide
b) Be a woman of non-childbearing potential (defined as
postmenopausal for > 2 years or having a screening FSH > 40 mIU/mL if
postmenopausal = 2 years or have had a hysterectomy, bilateral
oophorectomy, or documented ovarian failure).
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."
7 Male subjects must comply with the following requirements during the
study and for a duration of 90 days after last dose of study drug:
a) Subjects with female partners of childbearing potential (defined as
postmenopausal = 2 years or a non-menopausal female who has not had
a hysterectomy, bilateral oophorectomy, or documented ovarian failure)
must agree to utilize at least 1 acceptably effective contraceptive
method. At least 1 or more of the following methods are acceptable:
- surgical sterilization (i.e., vasectomy or bilateral tubal occlusion of a
female partner)
- placement of an IUD or IUS
- any form of hormonal contraception (oral, implantable, injectable,
intravaginal, or transdermal)
- use of a condom with or without spermicidal
foam/gel/film/cream/suppository
- partner's use of an occlusive cap [diaphragm, or cervical/vault caps]
with spermicidal foam/gel/film/cream/suppository)
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."
c) Male subjects who exclusively have male partners must consent to
using a condom during intercourse throughout the duration of the study
d) Must abstain from sperm donation during the study and for a per
Exclusion criteria:
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 of 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 Use of C1 INH, androgens, or tranexamic acid for prophylaxis of HAE attacks within the 7 days prior to the screening visit or initiation during the study. Androgen use is not permitted at any time during the study. Use of a C1 INH therapy for treatment of attacks is not excluded at any time.
4 Clinically significant abnormal ECG at the screening visit. This includes, but is not limited to, a QTcF > 470 msec, a PR > 220 msec, or ventricular and/or atrial premature contractions that are more frequent than occasional, and/or as couplets or higher in grouping.
5 Any clinically significant history of angina, myocardial infarction, syncope, clinically significant cardiac arrhythmias, left ventricular hypertrophy, cardiomyopathy, or any other cardiovascular abnormality.
6 Known family history of sudden death from causes other than HAE.
7 History of or current implanted defibrillator or pacemaker.
8 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 Creatinine clearance of = 60 mL/min or AST or ALT value = 2 times the upper limit of the normal reference range value obtained during screening is exclusionary.
9 Suspected C1INH resistance in the opinion of the Investigator and Sponsor.
10 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 alcoholic intake > 3 drinks/day).
11 Positive serology for human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
12 Pregnant, planning to become pregnant within 30 days of the study, or nursing.
13 Positive drugs of abuse screen (unless as used as medical treatment, e.g., with a prescription).
14 History of severe hypersensitivity to any medicinal product.


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: 20.0 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: 41.67-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

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: 83.33-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

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: 116.67-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

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: 125-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

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: 62.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

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 mil

Primary Outcome(s)

Main Objective: To evaluate the efficacy of once-daily prophylactic BCX7353 at up to 5 dose levels as measured by the number of attacks of hereditary angioedema (HAE) observed in patients with HAE enrolled in each treatment group

Timepoint(s) of evaluation of this end point: Day 28

Primary end point(s): Number of confirmed HAE attacks

Secondary Objective: To evaluate the safety and tolerability of BCX7353 over 28 days in subjects with HAE
To describe the pharmacokinetic (PK) profile of daily BCX7353 in subjects with HAE
To characterize the anticipated pharmacodynamic (PD) effects of BCX7353 in subjects with HAE
To characterize the dose-response relationship of BCX7353 in subjects with HAE
To evaluate effects of BCX7353 on quality of life

Secondary Outcome(s)

Secondary end point(s): Number of attacks requiring attack medication
Duration of attacks
Severity of attacks
Attack onset relative to the time of last dose of study drug
Discontinuations due to lack of efficacy
Symptoms and anatomical locations of attacks
Number of emergency room visits and/or hospitalizations
The number and proportion of subjects
- who discontinue due to a treatment-emergent AE
- who experience a treatment-emergent serious adverse event (SAE);
- who experience a Grade 3 or 4 treatment-emergent AE
- who experience treatment emergent Grade 3 or 4 laboratory abnormalities.

Timepoint(s) of evaluation of this end point: Throughout the study, post 28 days of treatment and post 2 weeks followup off treatment

Secondary ID(s)

2016-001272-29-GB

BCX7353-203

NCT02870972

Source(s) of Monetary Support

BioCryst Pharmaceuticals Inc