Overview

This trial is active, not recruiting.

Condition congestive heart failure
Treatments ad5.hac6, sucrose (3%)
Phase phase 1/phase 2
Sponsor Hammond, H. Kirk, M.D.
Collaborator National Heart, Lung, and Blood Institute (NHLBI)
Start date July 2010
End date January 2015
Trial size 56 participants
Trial identifier NCT00787059, 365, P01HL066941

Summary

This research study is designed to determine: 1) whether gene transfer using an agent called Ad5.hAC6 (adenovirus-5 encoding human adenylyl cyclase type 6) can be given safely to patients with congestive heart failure (CHF) and 2) whether this agent may be of benefit in heart failure. Gene transfer is a process by which genes are introduced into cells and the cells then produce the specific protein that the gene directs, in this case, a protein known as adenylyl cyclase type 6 (AC6). The gene is carried into the heart cells by a modified virus. The virus that is modified is an adenovirus (Ad5), a virus that sometimes causes a brief cold. In extensive animal experiments, it was found that increased amounts of AC6 protein in heart cells appeared to make the heart pump more vigorously.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Will receive intracoronary adenovirus encoding human adenylyl cyclase type 6
ad5.hac6
Intracoronary delivery of Ad5.hAC6 or sucrose solution (placebo) in 3:1 randomization (Ad5.hAC6 : placebo) with dose escalation, starting at 3.2 x 10^9 vp to 10^12 vp in 5 dose groups
(Placebo Comparator)
Will receive intracoronary sucrose solution
sucrose (3%)

Primary Outcomes

Measure
Combined: a) Exercise treadmill time; b) LV function by echocardiography before and during dobutamine infusion; c) Rate of LV pressure development and decline (dP/dt and -dP/dt) before and during dobutamine infusion.
time frame: Before, 4w, 12w

Secondary Outcomes

Measure
Symptoms (KCCQ); hemodynamics; ICD discharge frequency
time frame: Before, 4w, 12 w

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

Inclusion Criteria 1. Male or non-pregnant female patients aged 18-80 years of age 2. ≥3-month history of heart failure 3. Compensated (stable) CHF not on intravenous inotropes, vasodilators or diuretics, on optimal medical and device therapy as defined by AHA/ACC Guidelines 4. LV ejection fraction (on optimal therapy) no greater than 40% 5. Implanted cardiac defibrillator 6. At least one major coronary artery (or graft) with <50% proximal obstruction 7. Patients unable to walk (spinal injury, orthopedic problems) can be enrolled if all other criteria are met. 8. Women of child-bearing capacity must have a negative pregnancy test within 2 days of test substance administration, and female and male patients must be willing to use birth control during sex for 12w after test substance administration if the female partner is of child-bearing capacity. 9. Subjects willingly provide informed consent consistent with ICH-GCP guidelines Exclusion Criteria 1. Unstable or Class IV angina 2. Coronary revascularization planned or predicted in next 6 months 3. Ischemic myocardium in 3 or more regions of a single perfusion bed, as assessed by stress echocardiography or jeopardized viable myocardium >15% on perfusion imaging. 4. ≥50% occlusion of an "unprotected" left main coronary artery. If arterial or venous conduits provide blood flow to the distal left coronary circulation (ie, patent bypass grafts) then left main disease is "protected" and such patients are not excluded. The cardiologist performing the cardiac catheterization will make these decisions. 5. 2° AV Block (Mobitz 2) or 3° AV block unless pacemaker is present 6. Hospitalization for CHF requiring intravenous inotropes or vasodilators in the past 4 weeks 7. History of biopsy proven myocarditis 8. Myocardial infarction in previous 6 months 9. Restrictive, hypertrophic or infiltrative cardiomyopathy or chronic pericarditis 10. Previous or planned organ transplant recipient or donor. 11. Thrombocytopenia (<100,000 platelets/µl) or bleeding diathesis 12. COPD requiring supplemental oxygen at home 13. AST > 2 times upper limit of normal or chronic liver disease such as cirrhosis or Hepatitis C Virus (HCV). Patients with HCV are eligible only if both of two conditions are met: a) liver function tests are normal; AND b) liver biopsy is normal or shows only mild fibrosis. 14. Current or predicted hemodialysis within 12 months or estimated glomerular filtration rate (EGFR) <30 ml/min. On online EGFR calculator that uses sex, age, body weight and serum creatinine is available at: www.kidney.org/professionals/kdoqi/gfr_calculator.cfm. Use the higher of two EGFR results, which are based upon MDRD and CKD-EPI formulas. 15. CVA or TIA <6 months prior to enrollment 16. Patients who are immunosuppressed by medicines (corticosteroids, methotrexate, cyclophosphamide, cyclosporine), illnesses (AIDS, HIV), or neutrophil count <1000/mm3 17. Patients receiving other investigational drug therapy within 30 days of enrollment including gene transfer 18. Patients with diseases other than CHF that, in the opinion of the investigator, put the subject at risk or adversely affect the results

Additional Information

Official title Phase I/II Study AC6 Gene Transfer for Congestive Heart Failure
Principal investigator William Penny, MD
Description This research study is designed to determine: 1) whether gene transfer using an agent called Ad5.hAC6 (adenovirus-5 encoding human adenylyl cyclase type 6) can be given safely to patients with congestive heart failure (CHF) and 2) whether this agent may be of benefit in heart failure. Gene transfer is a process by which genes are introduced into cells and the cells then produce the specific protein that the gene directs, in this case, a protein known as adenylyl cyclase type 6 (AC6). The gene is carried into the heart cells by a modified virus. The virus that is modified is an adenovirus (Ad5), a virus that sometimes causes a brief cold. In extensive animal experiments, it was found that increased amounts of AC6 protein in heart cells appear to make the heart pump more vigorously.
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Hammond, H. Kirk, M.D..