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

This study is currently recruiting participants.
Verified February 2014 by Juventas Therapeutics, Inc.
Sponsor:
Information provided by (Responsible Party):
Juventas Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01961726
First received: October 8, 2013
Last updated: February 6, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Ischemic Heart Failure
Biological: Placebo
Biological: 30 mg dose of JVS-100
Biological: 45 mg dose of JVS-100
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Juventas Therapeutics, Inc.:

Primary Outcome Measures:
  • Impact of JVS-100 delivery on 6 minute walk distance at 4 month follow-up [ Time Frame: 4 Months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Impact of JVS-100 delivery on heart failure symptoms compared to placebo at 4 and/or 12 month follow-up [ Time Frame: 4 and/or 12 months ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Impact of JVS-100 delivery on quality of life measure at 4 month follow-up [ Time Frame: 4 Months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 72
Study Start Date: October 2013
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Placebo
Coronary Sinus Delivery
Biological: 45 mg dose of JVS-100
Coronary Sinus Delivery
Experimental: 45 mg dose of JVS-100 Biological: Placebo
Coronary Sinus Delivery
Biological: 30 mg dose of JVS-100
Coronary Sinus Delivery

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01961726

Contacts
Contact: Joseph Pastore, PhD 216-678-9003 jpastore@juventasinc.com

Locations
United States, Alabama
Cardiology, P.C. Recruiting
Birmingham, Alabama, United States, 35211
Contact: Susan DeRamus    205-780-4330 ext 338    sderamus@cardiologypc.com   
Principal Investigator: Farrell O Mendelsohn, MD         
United States, Florida
University of Florida Recruiting
Gainsville, Florida, United States, 32610-0277
Contact: Sarah Long    352-273-8196    Sarah.long@medicine.ufl.edu   
Principal Investigator: David Anderson, MD         
United States, Ohio
The Carl and Edyth Lindner Center for Research & Education at The Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Contact: David White, RN    513-585-1777      
Principal Investigator: Eugene Chung, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Patty Meldrum    801-585-6743      
Principal Investigator: Amit Patel, M.S., M.D.         
Sponsors and Collaborators
Juventas Therapeutics, Inc.
  More Information

No publications provided

Responsible Party: Juventas Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01961726     History of Changes
Other Study ID Numbers: JTCS-003
Study First Received: October 8, 2013
Last Updated: February 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Heart Failure
Ischemia
Heart Diseases
Cardiovascular Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 22, 2014