AC6 Gene Transfer in Patients With Reduced Left Ventricular Ejection Fraction Heart Failure

NCT03360448 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: RT-01-HF-REF
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To determine the safety and efficacy of an intracoronary injection of adenovirus 5 encoding human adenylyl cyclase 6 (RT-100) in patients with heart failure with reduced left ventricular ejection fraction (HFrEF) in a Phase 3 clinical trial.

Conditions

Heart Failure

Keywords

Gene Transfer

Outcome Measures

Primary Outcomes (1)

• Heart Failure Hospitalizations

  Reduce the event rate of all (first and repeat) heart failure hospitalizations

  Baseline to 12 months

Secondary Outcomes (4)

• Cardiovascular (CV) Death

  Baseline to 12 months

• All Cause Death

  Baseline to 12 months

• New York Heart Association (NYHA) Functional Classification

  Baseline to 12 months

• All Heart Failure (HF) Events

  Baseline to 12 months

Other Outcomes (5)

• Echocardiographic Parameters

  Baseline to 12 months

• Kansas City Cardiomyopathy Questionnaire (KCCQ)

  Baseline to 12 months

• Six Minute Walk Distance

  Baseline to 12 months

Study Arms (2)

Experimental

EXPERIMENTAL

Ad5.hAC6: Intracoronary delivery of adenovirus encoding human adenylyl cyclase type 6

Drug: Ad5.hAC6

Placebo Comparator

PLACEBO COMPARATOR

Placebo: Intracoronary delivery of formulation buffer ( 3% sucrose)

Drug: Placebo

Interventions

Ad5.hAC6 DRUG

1:1 randomization (Ad5.hAC6 : placebo) - intracoronary delivery

Also known as: RT-100

Experimental

Placebo DRUG

1:1 randomization (Ad5.hAC6 : placebo) - intracoronary delivery

Also known as: 3% sucrose

Placebo Comparator

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 80 years, inclusive, with history of heart failure (HF).
• Current HF symptoms with NYHA Functional Classification Class II to IV (inclusive) at Screening (Visit 1).
• Currently receiving optimally tolerated standard of care HF medical therapy as defined by the American Heart Association (AHA)/American College of Cardiology (ACC) Heart Failure guidelines and Focused Update along with an angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptor blockers (ARB), diuretics and sacubitril/valsartan for 4 weeks or longer, without change in drug therapy or dosage regimen, prior to Visit 1 (and continued same HF therapy through Visit 2).
• Left Ventricular Ejection Fraction (LVEF) ≥ 10 to ≤ 35% as determined by Screening echocardiogram (ECHO).
• NT pro BNP ≥ 400 pg/mL.
• If subject has had coronary artery bypass surgery, then at least one conduit must be patent and therefore be amendable for test article.
• Women of child bearing capacity must have a negative pregnancy test before 2 days of test article administration and must not be currently breastfeeding or nursing, and female and male patients must be willing to use birth control for 12 weeks after test article administration if the female partner is of child bearing capacity. Acceptable methods of effective birth control include total sexual abstinence; a condom with spermicide (men) in combination with barrier methods (diaphragm, cervical cap or cervical sponge); hormonal birth control (oral or injectable contraceptives); intrauterine devices; or surgical sterilization (vasectomy and testing that shows there is no sperm in the semen for men and bilateral tubal ligation +/- oophorectomy for women).
• Willing to provide informed consent consistent with International Conference on Harmonisation Good Clinical Practices.

You may not qualify if:

• Use of intravenous (IV) vasodilatory or inotropic therapy within 24 hours prior to Visit 2.
• Unstable angina within 3 months of Visit 1.
• Coronary revascularization planned or predicted within 6 months prior to Visit 1.
• Subjects who are candidates for revascularization are not considered appropriate for this trial; therefore, if a subject has Ischemia of viable myocardium \> 15% and is a candidate for revascularization, this subject would not be eligible to participate in this trial.
• Myocardial infarction within 6 months prior to Screening (Visit 1). Myocardial infarction is defined by documented evidence of a rise and/or fall of cardiac biomarker values (preferably cardiac troponin) with at least one value above the 99th percentile upper reference limit, and either ischemic symptoms, electrocardiogram changes, imaging evidence of loss of viable myocardium or new regional wall motion abnormality, or identification of an intracoronary thrombus by coronary angiography.
• Thrombocytopenia (\< 100,000 platelets/µL) or bleeding diathesis.
• Stroke or transient ischemic attack within 6 months prior to Screening (Visit 1).
• Use of sodium-glucose co-transporter 2 inhibitors used to treat type 2 diabetes mellitus.
• Cardiac:
• Biopsy documenting reversible cause of cardiomyopathy within 6 months of Visit 1 (Screening) if available as part of patient's prior cardiac history.
• Acute cardiac decompensation.
• If coronary angiogram within 6 months, with a presence of untreated severe three vessel coronary disease or unprotected left main coronary artery disease or coronary anatomy unsuitable for study procedure (eg, arterial tortuosity, etc) prior to Randomization (Visit 2).
• Use of IV diuretics within 12 hours of Randomization (Visit 2).
• Hemodynamically significant untreated valvular heart disease based on the AHA/ACC Valvular Heart Disease Guidelines.
• Current evidence of restrictive, peripartum, viral, infectious, infiltrative, or inflammatory cardiomyopathy.

Sponsors & Collaborators

• Renova Therapeutics: lead

Related Publications (1)

• Hammond HK, Penny WF, Traverse JH, Henry TD, Watkins MW, Yancy CW, Sweis RN, Adler ED, Patel AN, Murray DR, Ross RS, Bhargava V, Maisel A, Barnard DD, Lai NC, Dalton ND, Lee ML, Narayan SM, Blanchard DG, Gao MH. Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure: A Randomized Clinical Trial. JAMA Cardiol. 2016 May 1;1(2):163-71. doi: 10.1001/jamacardio.2016.0008.

  PMID: 27437887 BACKGROUND

MeSH Terms

Conditions

Heart Failure

Interventions

Sucrose

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized

Study Record Dates

• First Submitted: November 13, 2017
• First Posted: December 4, 2017
• Study Start: June 1, 2019
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2023
• Last Updated: June 7, 2019

Record last verified: 2019-06