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. (see Contacts and Locations)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 October 01, 2014