Juventas Retrograde

Overview

Status: Not yet recruiting
Keywords: Gene Therapy , Heart Failure , Regenerative Medicine , Cardiology
IRB Number: 00067119
Specialty: Cardiothoracic Surgery, Cardiothoracic Surgery, Cardiothoracic Surgery
Sub Specialties: Heart Stem Cell Therapy, Heart Failure

Brief Summary

 

The primary objective of this Phase I/II study is to assess the safety and clinical efficacy of delivering single doses of JVS-100 by a retrograde delivery infusion into the coronary sinus in subjects with chronic ischemic heart failure. The first 2 cohorts are open label. Subjects in the first cohort will receive 30 mgs of JVS-100 while patients in the second cohort will receive 45 mg of JVS-100. Following a safety DSMC review after 7 days following the completion of enrollment in each cohort, additional subjects will be randomized to receive either a single dose of JVS-100 (30 or 45 mg) or placebo in a parallel arm design. These results will be used to design a Phase IIb or Phase III clinical trial.

Primary Objectives

To assess safety and tolerability of single doses of JVS-100 delivered via retrograde coronary sinus administration through the Oscor Venos Occlusion Balloon catheter.

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 and/or quality of life measured by the Minnesota Living with Heart Failure Questionnaire compared to placebo at 4 months post dosing.

Secondary Objectives

To assess the impact of a single dose of JVS-100 on heart failure symptoms (e.g. quality of life and NYHA class), functional (e.g. 6 minute walk, treadmill exercise test), LV function (e.g. LVESV, LVEF), biomarker (e.g. NTproBNP) and morbidity/mortality (e.g. time to first heart failure decompensation, cardiovascular, and all-cause mortality) parameters compared to placebo at 4 and/or 12 months post dosing. 

 

Principal Investigator: Amit Patel
Department: Cardiothoracic Divison
Co Investigator: Anwar Tandar
Co Investigator: Rodney Badger

Contact Information

Name:Patty Meldrum
Phone: 801-581-4121
Email: patty.meldrum@hsc.utah.edu

Inclusion Criteria

 

Subject Inclusion Criteria

  •   Willing and able to sign informed consent

  •   Greater than or equal to 18 years of age

  •   Minnesota LWHF questionnaire score 20 points

  •   Subjects with 6 minute hall walk distance 400 m with the only limiting factors being related to cardiac fitness

  •   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:

o ACE inhibitor and/or ARB, and Beta-blocker for 90 days with stable dose* for

30 days unless contraindicated
o Diuretic in subjects with evidence of fluid retention o ASA unless contraindicated
o Statin unless contraindicated
o 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

 

Subject Exclusion Criteria

Planned revascularization within 30 days following enrollment
o 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*

Protocol #JTCS-003 43 Version 3.0 August 29, 2013

Juventas Therapeutics, Inc.
JVS-100 for the Treatment of Ischemic Heart Failure IND #14203

  •   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:

    o Known prior trauma to the coronary sinus
    o 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:
    o The cancer was limited to curable non-melanoma skin malignancies and/or

    o 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:

    o A stable, regular heart rate is maintained with a biventricular pacemaker o Astable,regularheartrateismaintainedwithauniventricularpacemaker

    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

    Protocol #JTCS-003 44 Version 3.0 August 29, 2013

Juventas Therapeutics, Inc.
JVS-100 for the Treatment of Ischemic Heart Failure IND #14203

  •   Subjects with a positive test results for hepatitis B/C and/or HIV will be excluded unless:

    o 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)
    o 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

    *estimated Glomerular Filtration Rate (eGFR) in ml/min is calculated using the subject’s serum creatinine value with the following equation57

    eGFR = 175 x (Serum Creatinine in mg/dL)-1.154 x (Age)-0.203 x (1.212 if subject is African American) x (0.742 if subject is female)