Study to Evaluate the Safety and Efficacy of JVS-100 Administered to Adults With Ischemic Heart Failure (RETRO-HF)

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

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 Overview

• Status: Unknown
• Conditions: Ischemic Heart Failure
• Intervention / Treatment: Biological: 30 mg dose of JVS-100; Biological: 45 mg dose of JVS-100; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Cardiology, P.C.
  • Florida
    • Gainsville, Florida, United States, 32610-0277
      • University of Florida
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Carl and Edyth Lindner Center for Research & Education at The Christ Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Biological: 30 mg dose of JVS-100; Coronary Sinus Delivery; Biological: 45 mg dose of JVS-100; Coronary Sinus Delivery
Experimental: 30 mg dose of JVS-100	Biological: 45 mg dose of JVS-100; Coronary Sinus Delivery; Biological: Placebo; Coronary Sinus Delivery
Experimental: 45 mg dose of JVS-100	Biological: 30 mg dose of JVS-100; Coronary Sinus Delivery; Biological: Placebo; Coronary Sinus Delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of JVS-100 delivery on 6 minute walk distance at 4 month follow-up	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.	4 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of JVS-100 delivery on heart failure symptoms compared to placebo at 4 and/or 12 month follow-up	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.	4 and/or 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of JVS-100 delivery on quality of life measure at 4 month follow-up	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 quality of life measure compared to placebo at 4 months post dosing.	4 Months

Collaborators and Investigators

• Sponsor: Juventas Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Anticipated): August 1, 2015
• Study Completion (Anticipated): August 1, 2015

Study Registration Dates

• First Submitted: October 8, 2013
• First Submitted That Met QC Criteria: October 9, 2013
• First Posted (Estimate): October 11, 2013

Study Record Updates

• Last Update Posted (Estimate): October 23, 2014
• Last Update Submitted That Met QC Criteria: October 22, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Heart Failure; Ischemia
• Other Study ID Numbers: JTCS-003