Clinical trial NCT01643590: Study to Evaluate the Safety and Efficacy of JVS-100 Administered to Adults With Ischemic Heart Failure.
Official title: A Phase II Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Efficacy of a Single Dose of JVS-100 Administered by Endomyocardial Injection to Cohorts of Adults With Ischemic Heart Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ischemic Heart Failure
Lead sponsor: Juventas Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2012-07-18
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo controlled Phase II study is designed to assess the safety and efficacy of using JVS-100 to treat heart failure.

Detailed description: 90 subjects with ischemic cardiomyopathy will be randomized to receive a single dose of 15 or 30 mg of JVS-100 or matching placebo. Subjects will be randomized 1:1:1 to receive either placebo, 15 mg or 30 mg of JVS-100. Subjects will be monitored overnight for 18-24 hours post dose and have scheduled visits at 3 days post-injection for safety evaluations. All subjects will be scheduled for follow-up visits at approximately 30 days (1 month), 120 days (4 months), and 360 days (12 months) to assess safety and cardiac function.

Eligibility criteria: Inclusion Criteria:

* Willing and able to sign informed consent
* Greater than or equal to 18 years of age
* Subjects with impaired 6 minute hall walk distance
* Impaired quality of life as measured by Minnesota LWHF questionnaire
* 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 ≤40% measured by echocardiography read at the echocardiography core laboratory
* Must meet wall thickness criteria
* Subject has an implanted, functional AICD
* Subjects with diabetes must have had an ophthalmologist exam within the last year showing no active proliferative retinopathy
* 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

Exclusion Criteria:

* Planned revascularization within 30 days following enrollment
* Estimated Glomerular Filtration Rate \< 30 ml/min\*
* Signs of acute heart failure within 24 hours of scheduled injection
* History of aortic valve regurgitation classified as "moderate" or severe
* Moderate/Severe aortic stenosis defined as AVA \<1.5 cm2

Note: Patient should not be excluded if the patient's medical records document that within the last 6 months the patient has either:

* no aortic stenosis
* mild aortic stenosis
* normal aortic valve
* normal aortic pressure gradient
* aortic pressure gradient \< 20 mmHg

  * Presence of an artificial aortic valve
  * Subjects with aortic aneurysm \>3.8 cm
  * 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 must have the following results on age appropriate cancer screenings:

* Subjects age 50 or older have had a Fecal occult blood test (FOBT) or fecal immunochemical test (FIT) that was negative within the last year
* Women age 30 or older have had a PAP test that was negative within the last 3 years
* Women age 40 or older have had a mammogram that was negative within the last year
* Men above age 45 have had a Prostate-Specific Antigen (PSA) blood test and digital rectal examination (DRE) that was negative within the last year
* At the request of the site principal investigator, any subject with a non-negative result thought to be due to a non-cancer-related condition will be evaluated by the medical monitor for enrollment

Exclusion Criteria (ctd):

* Subjects with persistent 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
* Subjects with Biventricular pacing device implant within the last 3 months OR previously implanted Biventricular pacing device with programming planned to be reoptimized following enrollment in this trial
* Previous solid organ transplant
* Subjects with greater than 40% univentricular RV Pacing
* Subjects with uncontrolled diabetes defined as HbA1c \>9.0%
* Inability to complete 6 minute walk or treadmill exercise test
* Participation in an experimental clinical trial within 30 days prior to enrollment
* Any subject who has been enrolled in a gene or stem cell therapy cardiac trial within the last year
* 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
* 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
* Any subject with a known existing LV thrombus or has an LV thrombus detected during the screening period of this study.
* Subjects with Rutherford class 5 or 6 critical limb ischemia
* Subject with severe chronic obstructive pulmonary disease (COPD)
* Any subject requiring home oxygen use
* Subjects with a history of Systemic Lupus Erythematosus (SLE) flare
* 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

Primary outcomes:
measure: Impact of JVS-100 injection on Six Minute Walk Distance (6MWD) at 4 month follow-up
timeFrame: 4 Months
measure: Impact of JVS-100 injection on Quality of Life at 4 month follow-up
timeFrame: 4 months
Secondary outcomes:
measure: Impact of JVS-100 Injection on Quality of Life
timeFrame: 12 Months
measure: Impact of JVS-100 Injection on NYHA class
timeFrame: 4 months
measure: Impact of JVS-100 Injection on LVEF
timeFrame: 4 months
measure: Impact of JVS-100 Injection on Time to First Heart Failure Decompensation
timeFrame: Up to 12 months
measure: Impact of JVS-100 Injection on Major Adverse Cardiac Events
timeFrame: Up to 12 months
measure: Impact of JVS-100 Injection on number of adverse events
timeFrame: Up to 12 months
measure: Impact of JVS-100 Injection on number of serious adverse events
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology PC
state: Alabama
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: Pepin Heart Institute
state: Florida
city: Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Saginaw
country: United States
facility: Michigan Cardiovascular Institute
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: St. Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Akron
country: United States
facility: Summa Health System
state: Ohio
city: Cincinnati
country: United States
facility: The Lindner Center at the Christ Hospital
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Healthcare
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
References: