Brief Summary
A phase I/II study to evaluate the safety and efficacy of JVS-100 administered by retrograde delivery to cohorts of adults with Ischemic Heart Failure.
Brief Title
Study to Evaluate the Safety and Efficacy of JVS-100 Administered to Adults With Ischemic Heart Failure
Detailed Description
72 subjects with ischemic cardiomyopathy. The Phase I portion (n=12 subjects) will be open label. In the first cohort, six subjects will receive a single dose of 30 mg of JVS-100 with a minimum of 3 days between each enrollment. After seven days following the enrollment of the last patient of cohort 1, a safety assessment by the DSMC will be performed. Upon DSMC approval, the second cohort of six subjects will receive a single dose of 45 mg of JVS-100 with a minimum of 3 days between each enrollment. After seven days following the enrollment of the last patient of cohort 2, a safety assessment by the DSMC will be performed. Upon DSMC approval, up to 60 subjects will be randomized (1:1:1) to receive a single dose of 30 mg or 45 mg of JVS-100 or matching placebo.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Ischemic Heart Failure
Eligibility Criteria
Inclusion Criteria:
* Willing and able to sign informed consent
* Greater than or equal to 18 years of age
* Poor quality of life as measured by the Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
* Impaired 6 Minute Walk test
* Ischemic cardiomyopathy without an acute coronary syndrome within the last 6 months
* Residual well-demarcated region of LV systolic dysfunction defined as at least 3 consecutive segments of abnormal wall motion by echocardiography read at the echocardiography core laboratory
* LVEF less than or equal to 40% measured by echocardiography read at the echocardiography core laboratory
* Subject receiving stable optimal pharmacological therapy defined as:
* ACE inhibitor and/or ARB, and Beta-blocker for 90 days with stable dose\* for
* 30 days unless contraindicated
* Diuretic in subjects with evidence of fluid retention
* ASA unless contraindicated
* Statin unless contraindicated
* Aldosterone antagonist per physician discretion
* Subject must not have a permanent device placed in the coronary sinus at the time of enrollment \*As defined as no more than 50% change in dose
Exclusion Criteria:
* Planned revascularization within 30 days following enrollment
* Note: if an angiographic study has been performed within the last year and the subject is enrolled, the angiography study report should be included as part of the subject's file
* Estimated Glomerular Filtration Rate \< 30 ml/min\*
* Signs of acute heart failure within 24 hours of scheduled infusion
* History of aortic valve regurgitation classified as "moderate-severe" or worse
* Patients will be excluded who have:
* Known prior trauma to the coronary sinus
* In dwelling instrumentation that may hamper coronary venous catheterization, including a biventricular pacing coronary sinus lead
* Mitral regurgitation defined as "severe" measured by echocardiography at the clinical site
* Patients with planned mitral valve repair or replacement surgery
* Any patient with a history of cancer will be excluded unless:
* The cancer was limited to curable non-melanoma skin malignancies and/or
* The cancer was removed by a successful tumor resection, with or without radiation or chemotherapy treatment, 5 years or more prior to enrollment in this study without recurrence.
* Subjects with persistent (per ACC/AHA/EEC guidelines)53, defined as recurrent AF episodes lasting longer than 7 days) or chronic atrial fibrillation will be excluded unless:
* A stable, regular heart rate is maintained with a biventricular pacemaker
* A stable, regular heart rate is maintained with a univentricular pacemaker pacing less than or equal to 40% of the time
* Inability to undergo 6 minute walk or treadmill exercise test
* Previous solid organ transplant
* Subjects with greater than 40% univentricular RV Pacing
* Subjects with uncontrolled diabetes defined as HbA1c \>10 %
* Participation in an experimental clinical trial within 30 days prior to enrollment
* Life expectancy of less than 1 year
* Positive pregnancy test (serum βHCG) in women of childbearing potential and/or unwillingness to use contraceptives or limit sexual activity as described in Section 8.2.1 below
* Unwillingness of men capable of fathering a child to agree to use barrier contraception or limit sexual activity as described in Section 8.2.1 below
* Subjects who are breast feeding
* Subjects with a positive test results for hepatitis B/C and/or HIV will be excluded unless:
* The subject is a carrier for hepatitis B/C but has never had an active flare
* Subjects with a history of Systemic Lupus Erythematosus (SLE) flare
* Total Serum Bilirubin \>4.0 mg/dl
* Aspartate aminotransferase (AST) \> 120 IU/L
* Alanine aminotransferase (ALT) \> 135 IU/L
* Alkaline phosphatase (ALP): \>300 IU/L
* Clinically significant elevations in PT or PTT relative to laboratory norms at day 0
* Critical limb ischemia that limits the patients from completing 6 minute walk or treadmill testing
* Subjects with severe chronic obstructive pulmonary disease (COPD)
* Severe defined as having been hospitalized for COPD within the last 12 months
* Any subject requiring home oxygen use for treatment of the symptoms of COPD
* History of drug or alcohol abuse within the last year
* A subject will be excluded if he/she is unfit for the trial based on the discretion of the site Principal Investigator
* Willing and able to sign informed consent
* Greater than or equal to 18 years of age
* Poor quality of life as measured by the Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
* Impaired 6 Minute Walk test
* Ischemic cardiomyopathy without an acute coronary syndrome within the last 6 months
* Residual well-demarcated region of LV systolic dysfunction defined as at least 3 consecutive segments of abnormal wall motion by echocardiography read at the echocardiography core laboratory
* LVEF less than or equal to 40% measured by echocardiography read at the echocardiography core laboratory
* Subject receiving stable optimal pharmacological therapy defined as:
* ACE inhibitor and/or ARB, and Beta-blocker for 90 days with stable dose\* for
* 30 days unless contraindicated
* Diuretic in subjects with evidence of fluid retention
* ASA unless contraindicated
* Statin unless contraindicated
* Aldosterone antagonist per physician discretion
* Subject must not have a permanent device placed in the coronary sinus at the time of enrollment \*As defined as no more than 50% change in dose
Exclusion Criteria:
* Planned revascularization within 30 days following enrollment
* Note: if an angiographic study has been performed within the last year and the subject is enrolled, the angiography study report should be included as part of the subject's file
* Estimated Glomerular Filtration Rate \< 30 ml/min\*
* Signs of acute heart failure within 24 hours of scheduled infusion
* History of aortic valve regurgitation classified as "moderate-severe" or worse
* Patients will be excluded who have:
* Known prior trauma to the coronary sinus
* In dwelling instrumentation that may hamper coronary venous catheterization, including a biventricular pacing coronary sinus lead
* Mitral regurgitation defined as "severe" measured by echocardiography at the clinical site
* Patients with planned mitral valve repair or replacement surgery
* Any patient with a history of cancer will be excluded unless:
* The cancer was limited to curable non-melanoma skin malignancies and/or
* The cancer was removed by a successful tumor resection, with or without radiation or chemotherapy treatment, 5 years or more prior to enrollment in this study without recurrence.
* Subjects with persistent (per ACC/AHA/EEC guidelines)53, defined as recurrent AF episodes lasting longer than 7 days) or chronic atrial fibrillation will be excluded unless:
* A stable, regular heart rate is maintained with a biventricular pacemaker
* A stable, regular heart rate is maintained with a univentricular pacemaker pacing less than or equal to 40% of the time
* Inability to undergo 6 minute walk or treadmill exercise test
* Previous solid organ transplant
* Subjects with greater than 40% univentricular RV Pacing
* Subjects with uncontrolled diabetes defined as HbA1c \>10 %
* Participation in an experimental clinical trial within 30 days prior to enrollment
* Life expectancy of less than 1 year
* Positive pregnancy test (serum βHCG) in women of childbearing potential and/or unwillingness to use contraceptives or limit sexual activity as described in Section 8.2.1 below
* Unwillingness of men capable of fathering a child to agree to use barrier contraception or limit sexual activity as described in Section 8.2.1 below
* Subjects who are breast feeding
* Subjects with a positive test results for hepatitis B/C and/or HIV will be excluded unless:
* The subject is a carrier for hepatitis B/C but has never had an active flare
* Subjects with a history of Systemic Lupus Erythematosus (SLE) flare
* Total Serum Bilirubin \>4.0 mg/dl
* Aspartate aminotransferase (AST) \> 120 IU/L
* Alanine aminotransferase (ALT) \> 135 IU/L
* Alkaline phosphatase (ALP): \>300 IU/L
* Clinically significant elevations in PT or PTT relative to laboratory norms at day 0
* Critical limb ischemia that limits the patients from completing 6 minute walk or treadmill testing
* Subjects with severe chronic obstructive pulmonary disease (COPD)
* Severe defined as having been hospitalized for COPD within the last 12 months
* Any subject requiring home oxygen use for treatment of the symptoms of COPD
* History of drug or alcohol abuse within the last year
* A subject will be excluded if he/she is unfit for the trial based on the discretion of the site Principal Investigator
Inclusion Criteria
Inclusion Criteria:
* Willing and able to sign informed consent
* Greater than or equal to 18 years of age
* Poor quality of life as measured by the Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
* Impaired 6 Minute Walk test
* Ischemic cardiomyopathy without an acute coronary syndrome within the last 6 months
* Residual well-demarcated region of LV systolic dysfunction defined as at least 3 consecutive segments of abnormal wall motion by echocardiography read at the echocardiography core laboratory
* LVEF less than or equal to 40% measured by echocardiography read at the echocardiography core laboratory
* Subject receiving stable optimal pharmacological therapy defined as:
* ACE inhibitor and/or ARB, and Beta-blocker for 90 days with stable dose\* for
* 30 days unless contraindicated
* Diuretic in subjects with evidence of fluid retention
* ASA unless contraindicated
* Statin unless contraindicated
* Aldosterone antagonist per physician discretion
* Subject must not have a permanent device placed in the coronary sinus at the time of enrollment \*As defined as no more than 50% change in dose
* Willing and able to sign informed consent
* Greater than or equal to 18 years of age
* Poor quality of life as measured by the Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
* Impaired 6 Minute Walk test
* Ischemic cardiomyopathy without an acute coronary syndrome within the last 6 months
* Residual well-demarcated region of LV systolic dysfunction defined as at least 3 consecutive segments of abnormal wall motion by echocardiography read at the echocardiography core laboratory
* LVEF less than or equal to 40% measured by echocardiography read at the echocardiography core laboratory
* Subject receiving stable optimal pharmacological therapy defined as:
* ACE inhibitor and/or ARB, and Beta-blocker for 90 days with stable dose\* for
* 30 days unless contraindicated
* Diuretic in subjects with evidence of fluid retention
* ASA unless contraindicated
* Statin unless contraindicated
* Aldosterone antagonist per physician discretion
* Subject must not have a permanent device placed in the coronary sinus at the time of enrollment \*As defined as no more than 50% change in dose
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01961726
Org Class
Industry
Org Full Name
Juventas Therapeutics, Inc.
Org Study Id
JTCS-003
Overall Status
Unknown status
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase I/II Study to Evaluate the Safety and Efficacy of JVS-100 Administered by Retrograde Delivery to Cohorts of Adults With Ischemic Heart Failure
Primary Outcomes
Outcome Description
To investigate the impact of single doses of JVS-100 (either 30 or 45 mg) delivered retrograde via the coronary sinus through the Oscor Venos Occlusion Balloon catheter on 6 minute walk distance compared to placebo at 4 months post dosing.
Outcome Measure
Impact of JVS-100 delivery on 6 minute walk distance at 4 month follow-up
Outcome Time Frame
4 Months
Secondary Outcomes
Outcome Description
To assess the impact of a single dose of JVS-100 on heart failure symptoms compared to placebo at 4 and/or 12 months post-dosing.
Outcome Time Frame
4 and/or 12 months
Outcome Measure
Impact of JVS-100 delivery on heart failure symptoms compared to placebo at 4 and/or 12 month follow-up
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jooyoung Shin
Investigator Email
jushin@montefiore.org
Investigator Phone