Clinical trial NCT01961726: Study to Evaluate the Safety and Efficacy of JVS-100 Administered to Adults With Ischemic Heart Failure
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Ischemic Heart Failure
Lead sponsor: Juventas Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2013-10-11
Enrollment: 72
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: 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.

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.

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

Primary outcomes:
measure: Impact of JVS-100 delivery on 6 minute walk distance at 4 month follow-up
timeFrame: 4 Months
Secondary outcomes:
measure: Impact of JVS-100 delivery on heart failure symptoms compared to placebo at 4 and/or 12 month follow-up
timeFrame: 4 and/or 12 months
Other outcomes:
measure: Impact of JVS-100 delivery on quality of life measure at 4 month follow-up
timeFrame: 4 Months
Locations:
city: Birmingham
country: United States
facility: Cardiology, P.C.
state: Alabama
city: Gainsville
country: United States
facility: University of Florida
state: Florida
city: Cincinnati
country: United States
facility: The Carl and Edyth Lindner Center for Research & Education at The Christ Hospital
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
References: