Study to Evaluate the Safety of a Single Escalating Dose of ACRX-100 in Adults With Ischemic Heart Failure

Juventas Therapeutics

Status and phase

Completed

Phase 1

Conditions

Heart Failure

Treatments

Biological: ACRX-100

Study type

Interventional

Funder types

Industry

Identifiers

NCT01082094

JTCS-001

Details and patient eligibility

About

The purpose of this Phase 1 study is to assess the safety, tolerability, and preliminary efficacy of single escalating doses of ACRX-100 delivered via endomyocardial injection in adults with ischemic heart failure.

Full description

This open label, 16 subject, Phase 1 dose-escalation study will demonstrate the initial safety of using ACRX-100 to treat heart failure in subjects with ischemic cardiomyopathy. Safety will be tracked at each dose by documenting all adverse events (AEs), with the primary safety endpoint being the number of major cardiac AEs at 30 days. In each cohort (n=4 in low dose, n=6 each in mid and high dose), subjects will receive a single dose of ACRX-100. Preliminary efficacy will be evaluated by measuring the impact on cardiac function via standard echocardiography measurements, cardiac perfusion via SPECT imaging, and improvement in NYHA classification.

Enrollment

17 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Greater than or equal to 18 years of age
NYHA Class III
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
No left ventricular wall thickness less than 0.5 cm measured by echocardiography read at the echocardiography core laboratory
Mitral regurgitation of 0-2+ (inclusive) measured by echocardiography read at the echocardiography core laboratory
Subject has an implanted, functional AICD
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 contraindicate
- Diuretic in subjects with evidence of fluid retention ASA unless contraindicated
- Statin unless contraindicated
- Aldosterone antagonist per physician discretion unless contraindicated
Subjects with found diagnosis of diabetes must have had an ophthalmologist exam within the last year showing no active proliferative retinopathy

Exclusion criteria

Planned revascularization within 30 days following enrollment
Estimated Glomerular Filtration Rate < 30 ml/min*
Inability to undergo SPECT imaging
History of aortic valve regurgitation > 2
Moderate/Severe aortic stenosis defined as AVA <1.5 cm2
Presence of an artificial aortic valve
Subjects with aortic aneurysm >3.8 cm
History of cancer with exception of basal cell carcinoma and following results on age appropriate cancer screenings
Subjects with persistent atrial fibrillation (per ACC/AHA/ESC guidelines, defined as recurrent AF episodes lasting longer than 7 days)
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%
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
Unwillingness of men capable of fathering a child to agree to use barrier contraception or limit sexual activity
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
Proteinuria > 3.5 g/L
Any subject with a known existing LV thrombus or has an LV thrombus detected during the screening period of this study. Presence of LV thrombus will be determined by echocardiography and the addition of echo-contrast if any question remains after non-contrast echocardiogram.
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 equation : eGFR = 186 x (serum creatinine in mg/dl)-1.154 x (Age)-.2303 x (Age) x (1.210 if subject is black) x (0.742 if subject is female)