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

Ischemic Heart Failure Clinical Trial

— RETRO-HF  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01961726
• Other study ID #: JTCS-003
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: October 8, 2013
• Last updated: October 22, 2014
• Start date: October 2013
• Est. completion date: August 2015

Study information

• Verified date: October 2014
• Source: Juventas Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 72
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 ßHCG) 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

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

Related Conditions & MeSH terms

• Heart Failure
• Ischemia
• Ischemic Heart Failure

Intervention

Biological:
• Placebo
Coronary Sinus Delivery
• 30 mg dose of JVS-100
Coronary Sinus Delivery
• 45 mg dose of JVS-100
Coronary Sinus Delivery

Locations

Country	Name	City	State
United States	Cardiology, P.C.	Birmingham	Alabama
United States	The Carl and Edyth Lindner Center for Research & Education at The Christ Hospital	Cincinnati	Ohio
United States	University of Florida	Gainsville	Florida
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Juventas Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Primary	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	No
Secondary	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	No