| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10019860 |
| E.1.2 | Term | Hereditary angioedema |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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 |
|
| E.2.2 | Secondary objectives of the trial |
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
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 <<BLINDED>> HAE attacks per
month for <<BLINDED>> 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 period
of 90 days after last dose of study drug.
8 Any concomitant medication recorded at the screening visit and not
stated as prohibited 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.
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 including diary recording of HAE attacks beginning at the
screening visit |
|
| E.4 | Principal 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Number of confirmed HAE attacks |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | 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. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Throughout the study, post 28 days of treatment and post 2 weeks followup off treatment |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Canada |
| European Union |
| Macedonia, the former Yugoslav Republic of |
| Switzerland |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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