A clinical trial with GS-6615 for treatment of Symptomatic Hypertrophic Cardiomyopathy

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2013-004429-97-GB
• Date of registration: 05/11/2014
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: A clinical trial with GS-6615 for treatment of Symptomatic Hypertrophic Cardiomyopathy
• Scientific title: A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of GS-6615 on Exercise Capacity in Subjects with Symptomatic Hypertrophic Cardiomyopathy
• Date of first enrolment: 24/03/2015
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004429-97
• 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: 2
• 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, France, Germany, Israel, Italy, Netherlands, United Kingdom, United States

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1) Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
2) Males and females 18 to 65 years old, inclusive
3) Established diagnosis of Hypertrophic Cardiomyopathy defined by standard criteria as a maximal LV wall thickness = 15mm at initial diagnosis in the absence of other causative loading abnormalities capable of producing the magnitude of hypertrophy observed
4) Exertional symptoms including at least one of the following:
a) New York Heart Association (NYHA) Class = II Dyspnea
b) Canadian Cardiovascular Society (CCS) Class = II Angina
5) Screening (baseline) Peak VO2 < 80% of predicted for age, sex, and weight-adjusted equations, as confirmed by the investigator
6) Ability to perform an upright treadmill cardiopulmonary exercise test (CPET)
7) Hemodynamically stable at both Screening and Randomization visits defined as: systolic blood pressure = 90 mmHg, HR = 100 beats/min, and not requiring mechanical circulatory support or intravenous treatment with diuretics or vasoactive drugs
8) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to utilize protocol-specified method(s) of contraception

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 171
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

Exclusion criteria:
1) Known aortic valve stenosis (moderate or severe) confirmed by echocardiogram
2) Known coronary artery disease (defined as = 50% stenosis in = 1 epicardial coronary artery)
3) Left ventricular systolic dysfunction (ejection fraction < 50%), known or detected during Screening visit
4) Known moderate or severe Chronic Obstructive Pulmonary Disease (defined as FEV1 < 80% predicted)
5) Known moderate or severe restrictive lung disease (defined as total lung capacity < 70% predicted)
6) Recent septal reduction procedure (ie, surgical myectomy or alcohol septal ablation) within six months prior to Screening or such a procedure scheduled to occur during the study
7) Atrial fibrillation on 12-lead ECG at Screening or detected during Randomization visit. Subjects with paroxysmal atrial fibrillation in whom sinus rhythm is restored may be re-screened at a later date.
8) Known or suspected infiltrative myocardial disease or glycogen storage disorder
9) Body mass index (BMI) = 36 kg/m2
10) Severe renal impairment at Screening (defined as an estimated GFR < 30 mL/min/1.73m2 as calculated by the Modification of Diet in Renal Disease [MDRD] equation by the central laboratory)
11) Abnormal liver function tests at Screening, defined as ALT or AST > 2xULN, or total bilirubin > 1.5xULN
12) Known or suspected history of seizures or epilepsy
13) Use of Class I antiarrhythmic drugs, including disopyramide, within 7 days prior to Screening
14) Use of ranolazine within 7 days prior to Screening
15) Use of concomitant treatment with drugs or products that are strong inhibitors or inducers of CYP3A within 5- half-lives prior to Screening
16) Known hypersensitivity to study drug (GS-6615 or placebo), its metabolites, or formulation excipient
17) Females who are pregnant or breastfeeding. Lactating females must agree to discontinue nursing before the study drug is administered. A negative serum pregnancy test at Screening and a negative urine pregnancy test at Randomization visit are required for female subjects of childbearing potential.
18) In the judgment of the investigator, any clinically significant ongoing medical condition that might jeopardize the subject’s safety or interfere with the study, including participation in another investigational drug or investigational device study within the 30 days prior to Screening with potential residual effects that might confound the results of this study
19) Any condition that in the opinion of the investigator would preclude compliance with the study protocol


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Subjects with symptoms (NYHA Class = II dyspnea or CCS Class = II angina) due to hypertrophic cardiomyopathy (defined by standard criteria as a maximal LV wall thickness of = 15 mm in the absence of other causative loading abnormalities capable of producing the magnitude of hypertrophy observed)
MedDRA version: 19.0 Level: PT Classification code 10020871 Term: Hypertrophic cardiomyopathy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: GS-6615 3 mg White
Product Code: GS-6615 3 mg White
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: No INN or proposed INN available
CAS Number: 1443211-72-0
Current Sponsor code: GS-6615
Other descriptive name: CAS Name: 1,4-Benzoxazepin-5(2H)-one, 3,4-dihydro-4-(2-pyrimidinylmethyl)-7-[4-(trifluoromethoxy)phenyl] IUPAC Name: 4-(Pyrimidin-2-ylmethyl)-7-[4-(trifluoromethoxy)phenyl]-3,4-dihydro-1,4-benzoxazepin-5(2H)-one
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: GS-6615 6 mg White
Product Code: GS-6615 6 mg White
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: No INN or proposed INN available
CAS Number: 1443211-72-0
Current Sponsor code: GS-6615
Other descriptive name: CAS Name: 1,4-Benzoxazepin-5(2H)-one, 3,4-dihydro-4-(2-pyrimidinylmethyl)-7-[4-(trifluoromethoxy)phenyl] IUPAC Name: 4-(Pyrimidin-2-ylmethyl)-7-[4-(trifluoromethoxy)phenyl]-3,4-dihydro-1,4-benzoxazepin-5(2H)-one
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 6-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: GS-6615 3 mg Pink
Product Code: GS-6615 3 mg Pink
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: No INN or proposed INN available
CAS Number: 1443211-72-0
Current Sponsor code: GS-6615
Other descriptive name: CAS Name: 1,4-Benzoxazepin-5(2H)-one, 3,4-dihydro-4-(2-pyrimidinylmethyl)-7-[4- (trifluoromethoxy)phenyl] IUPAC Name: 4-(Pyrimidin-2-ylmethyl)-7-[4- (trifluoromethoxy)phenyl]-3,4-dihydro-1,4-benzoxazepin-5(2H)-one
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-

Primary Outcome(s)

Main Objective: The primary objective of this study is to evaluate the effect of GS-6615 on exercise capacity, as measured by Peak VO2 achieved during cardiopulmonary exercise testing (CPET), in subjects with symptomatic hypertrophic cardiomyopathy.

Secondary Objective: The secondary objectives of this study are to:
• Evaluate the safety and tolerability of GS-6615 in subjects with symptomatic hypertrophic cardiomyopathy.
• Evaluate the effect of GS-6615 on quality of life as measured by the Minnesota Living With Heart Failure Questionnaire (MLHFQ).
• Evaluate the effect of GS-6615 on treadmill exercise time during CPET.

Primary end point(s): The primary efficacy endpoint is the change in Peak VO2 from baseline (Screening) to Week 24.

Timepoint(s) of evaluation of this end point: Monitoring will be conducted on subject in the clinic at Screening and Week 24.

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints are:
• Change in MLHFQ from baseline to Week 24.
• Change in treadmill exercise time from baseline to Week 24.
• Change in Peak VO2 from baseline to Week 12.
• Change in the MLHFQ from baseline to Week 12.
• Change in treadmill exercise time from baseline to Week 12.

The safety endpoints include mortality and appropriate ICD interventions (shock or anti-tachycardia pacing), AEs, vital signs, clinical laboratory tests, and ECG data (PR, RR, QRS, QT and QTc interval).

Timepoint(s) of evaluation of this end point: Monitoring will be conducted on subject in the clinic at Screening, Randomization (Day 1 of the Treatment period), during the treatment period at Week 2, Week 6, Week 12, Week 18, Week 24, and every 12 weeks after Week 24 through End of Double-Blind Treatment visit.

Secondary ID(s)

GS-US-361-1157

NCT02291237

Source(s) of Monetary Support

Gilead Sciences, Inc.