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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Juventas Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01082094
First received: March 4, 2010
Last updated: June 5, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Heart Failure
Biological: ACRX-100
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Dose Escalation Study to Evaluate the Safety of a Single Escalating Dose of ACRX-100 Administered by Endomyocardial Injection to Cohorts of Adults With Ischemic Heart Failure

Resource links provided by NLM:


Further study details as provided by Juventas Therapeutics, Inc.:

Primary Outcome Measures:
  • Number of Major Adverse Cardiac Events (MACE) at 30 days post-injection [ Time Frame: 30 days post-injection ] [ Designated as safety issue: Yes ]

Enrollment: 17
Study Start Date: February 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACRX-100

Cohort 1 = Low dose

Cohort 2 = Middle dose

Cohort 3 = High Dose

Biological: ACRX-100
Three cohorts (16 total subjects) will be studied. There will be no concurrent controls. The dose will be escalated by increasing the total amount of ACRX-100 delivered per subject from low dose (n=4 subjects) to middle dose (n=6 subjects) to high dose (n=6 subjects). ACRX-100 will be injected directly into the myocardium as a single dose at multiple sites through a percutaneous, left ventricular approach using a needle injection catheter.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01082094

Locations
United States, Alabama
Cardiology, PC
Birmingham, Alabama, United States, 35211
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Juventas Therapeutics, Inc.
Investigators
Principal Investigator: Douglas Losordo, MD Northwestern University
  More Information

No publications provided

Responsible Party: Juventas Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01082094     History of Changes
Other Study ID Numbers: JTCS-001
Study First Received: March 4, 2010
Last Updated: June 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Juventas Therapeutics, Inc.:
Ischemic heart failure
Congestive heart failure
Stromal cell-derived factor 1
SDF-1
Gene therapy

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 29, 2014