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

Phase 1

• Conditions: Ischemic Heart Failure
• Interventions: Biological: 30 mg dose of JVS-100; Biological: Placebo; Biological: 45 mg dose of JVS-100

• Registration Number: NCT01961726
• Lead Sponsor: Juventas Therapeutics, Inc.

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.

Study Timeline

• Study Start: 2013-10
• Study First Submitted: 2013-10-08
• Study First Submitted QC: 2013-10-09
• Study First Posted: 2013-10-11
• Status Verified: 2014-10
• Last Update Submitted: 2014-10-22
• Last Update Posted: 2014-10-23
• Primary Completion: 2015-08
• Study Completion: 2015-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 72

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
30 mg dose of JVS-100	45 mg dose of JVS-100	-
Placebo	30 mg dose of JVS-100	-
30 mg dose of JVS-100	Placebo	-
Placebo	45 mg dose of JVS-100	-
45 mg dose of JVS-100	Placebo	-
45 mg dose of JVS-100	30 mg dose of JVS-100	-

Primary Outcome Measures

Name	Time	Method
Impact of JVS-100 delivery on 6 minute walk distance at 4 month follow-up	4 Months	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

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

Trial Locations

Locations (4)

The Carl and Edyth Lindner Center for Research & Education at The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

University of Florida; 🇺🇸 Gainsville, Florida, United States

Cardiology, P.C.; 🇺🇸 Birmingham, Alabama, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States