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

Juventas Therapeutics

Status and phase: Unknown; Phase 2

Conditions: Ischemic Heart Failure

Treatments: Biological: Placebo Injection; Biological: JVS-100 30 mg dose injection; Biological: JVS-100 15 mg dose Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT01643590

JTCS-004

Details and patient eligibility

About

This is a randomized, double-blind, placebo controlled Phase II study is designed to assess the safety and efficacy of using JVS-100 to treat heart failure.

Full description

90 subjects with ischemic cardiomyopathy will be randomized to receive a single dose of 15 or 30 mg of JVS-100 or matching placebo. Subjects will be randomized 1:1:1 to receive either placebo, 15 mg or 30 mg of JVS-100. Subjects will be monitored overnight for 18-24 hours post dose and have scheduled visits at 3 days post-injection for safety evaluations. All subjects will be scheduled for follow-up visits at approximately 30 days (1 month), 120 days (4 months), and 360 days (12 months) to assess safety and cardiac function.

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Willing and able to sign informed consent

• Greater than or equal to 18 years of age

• Subjects with impaired 6 minute hall walk distance

• Impaired quality of life as measured by Minnesota LWHF questionnaire

• 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 ≤40% measured by echocardiography read at the echocardiography core laboratory

• Must meet wall thickness criteria

• Subject has an implanted, functional AICD

• Subjects with diabetes must have had an ophthalmologist exam within the last year showing no active proliferative retinopathy

• 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

Exclusion criteria

• Planned revascularization within 30 days following enrollment
• Estimated Glomerular Filtration Rate < 30 ml/min*
• Signs of acute heart failure within 24 hours of scheduled injection
• History of aortic valve regurgitation classified as "moderate" or severe
• Moderate/Severe aortic stenosis defined as AVA <1.5 cm2

Note: Patient should not be excluded if the patient's medical records document that within the last 6 months the patient has either:

• no aortic stenosis

• mild aortic stenosis

• normal aortic valve

• normal aortic pressure gradient

• aortic pressure gradient < 20 mmHg

  • Presence of an artificial aortic valve
  • Subjects with aortic aneurysm >3.8 cm
  • 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 must have the following results on age appropriate cancer screenings:

• Subjects age 50 or older have had a Fecal occult blood test (FOBT) or fecal immunochemical test (FIT) that was negative within the last year
• Women age 30 or older have had a PAP test that was negative within the last 3 years
• Women age 40 or older have had a mammogram that was negative within the last year
• Men above age 45 have had a Prostate-Specific Antigen (PSA) blood test and digital rectal examination (DRE) that was negative within the last year
• At the request of the site principal investigator, any subject with a non-negative result thought to be due to a non-cancer-related condition will be evaluated by the medical monitor for enrollment

Exclusion Criteria (ctd):

• Subjects with persistent 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

• Subjects with Biventricular pacing device implant within the last 3 months OR previously implanted Biventricular pacing device with programming planned to be reoptimized following enrollment in this trial

• Previous solid organ transplant

• Subjects with greater than 40% univentricular RV Pacing

• Subjects with uncontrolled diabetes defined as HbA1c >9.0%

• Inability to complete 6 minute walk or treadmill exercise test

• Participation in an experimental clinical trial within 30 days prior to enrollment

• Any subject who has been enrolled in a gene or stem cell therapy cardiac trial within the last year

• 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

• 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

• Any subject with a known existing LV thrombus or has an LV thrombus detected during the screening period of this study.

• Subjects with Rutherford class 5 or 6 critical limb ischemia

• Subject with severe chronic obstructive pulmonary disease (COPD)

• Any subject requiring home oxygen use

• Subjects with a history of Systemic Lupus Erythematosus (SLE) flare

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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90 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Biological: Placebo Injection

15 mg dose of JVS-100

Experimental group

Description:

15 mg dose of JVS-100

Treatment:

Biological: JVS-100 15 mg dose Injection

30 mg dose of JVS-100

Experimental group

Description:

30 mg dose of JVS-100

Treatment:

Biological: JVS-100 30 mg dose injection