Brief Summary
To evaluate the safety of retrograde coronary sinus infusion (RCSI) of a novel triple-effector plasmid (INXN-4001) in outpatient LVAD recipients as assessed by incidence of all study intervention-related adverse events occurring up to 6 months post-RCSI (primary endpoints), and to evaluate general safety by assessing incidence of cardiac specific adverse events and the incidence of related serious adverse events at intervals up to 12 months post-infusion (or until cardiac transplantation or death).
Brief Title
Novel INXN-4001 Triple Effector Plasmid in Heart Failure
Detailed Description
This is a first-in-human, phase I, open label, safety study of INXN-4001 delivered via RCSI in patients with outpatient LVAD. Twelve stable patients with implanted LVAD for mechanical support of end stage heart failure have been allocated into 2 cohorts (6 subjects each) to evaluate the safety of infusing the same amount of INXN-4001 (80mg) in 2 volumes (40mL and 80mL) at 20mL/min rate. Ongoing safety assessments include clinical labs, physical exams, ECG and medical history collected during clinic visits at: pre-treatment, day 3, then 1, 3, 6, 9, and 12 months after dosing via RCSI. During visits, subjects complete the KCCQ questionnaire and are evaluated via 6-min walk test (6MWT) prior to and during an LVAD wean interval. Daily activity data is collected throughout the study using a wearable biosensor (Actigraph).
Categories
Completion Date
Completion Date Type
Actual
Conditions
Heart Failure
Cardiovascular Diseases
Heart-Assist Device
Eligibility Criteria
Inclusion Criteria:
* Male and female adult patients with a stable LVAD implanted for end-stage heart failure
* Must be managed in an outpatient setting and on stable medication regimen
Exclusion Criteria:
* Women who are pregnant or nursing
* Patients who have been on another clinical trial for heart failure in the last 90 days, or have received any stem cell or gene therapy within the previous year.
* Patient is not able to complete a Six Minute Walk Test or unable to tolerate an LVAD wean in the past 3 months
* Patient has an active infection requiring systemic antibiotics or an autoimmune disease requiring systemic immunosuppressants
* Patient has a history of arrhythmia, uncontrolled diabetes, diabetic retinopathy, systemic lupus erythematosus, macular degeneration, hyper-coagulation, or stroke
* Patient has had a myocardial infarction related to ischemia within the past 30 days
* Patient has had certain prior surgeries such as organ transplant, cardiac transplantation, left ventricle reduction surgery, or cardiomyoplasty
* Patient has infectious disease, such as hepatitis B or C, or human immunodeficiency virus (HIV)
* Patient has a history of cancer within the past 3 years
* Male and female adult patients with a stable LVAD implanted for end-stage heart failure
* Must be managed in an outpatient setting and on stable medication regimen
Exclusion Criteria:
* Women who are pregnant or nursing
* Patients who have been on another clinical trial for heart failure in the last 90 days, or have received any stem cell or gene therapy within the previous year.
* Patient is not able to complete a Six Minute Walk Test or unable to tolerate an LVAD wean in the past 3 months
* Patient has an active infection requiring systemic antibiotics or an autoimmune disease requiring systemic immunosuppressants
* Patient has a history of arrhythmia, uncontrolled diabetes, diabetic retinopathy, systemic lupus erythematosus, macular degeneration, hyper-coagulation, or stroke
* Patient has had a myocardial infarction related to ischemia within the past 30 days
* Patient has had certain prior surgeries such as organ transplant, cardiac transplantation, left ventricle reduction surgery, or cardiomyoplasty
* Patient has infectious disease, such as hepatitis B or C, or human immunodeficiency virus (HIV)
* Patient has a history of cancer within the past 3 years
Inclusion Criteria
Inclusion Criteria:
* Male and female adult patients with a stable LVAD implanted for end-stage heart failure
* Must be managed in an outpatient setting and on stable medication regimen
* Male and female adult patients with a stable LVAD implanted for end-stage heart failure
* Must be managed in an outpatient setting and on stable medication regimen
Gender
All
Gender Based
false
Keywords
retrograde coronary sinus infusion
DNA
non-viral
triple effector plasmid
gene therapy
regenerative medicine
non-stem cell
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03409627
Org Class
Industry
Org Full Name
Triple-Gene, LLC
Org Study Id
INXN-4001-001
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase I, Open Label, Safety Study of INXN-4001 Delivered Via Retrograde Coronary Sinus Infusion in Patients With an Outpatient Left Ventricular Assist Device (LVAD)
Primary Outcomes
Outcome Description
As assessed by incidence of all study intervention-related adverse events occurring up to 6 months post- treatment intervention-related adverse events
Outcome Measure
To evaluate safety and feasibility of INXN-4001
Outcome Time Frame
6 months
Secondary Outcomes
Outcome Description
Improvement in 6 minute walk duration and distance
Outcome Time Frame
12 months
Outcome Measure
Wean tolerability following treatment with INXN-4001
Outcome Description
Change in Kansas City Cardiomyopathy Questionnaire responses
Outcome Time Frame
12 months
Outcome Measure
Quality of Life following treatment with INXN-4001
Outcome Description
Ability to collect daily activity level as measured by wearable biosensor
Outcome Time Frame
12 months
Outcome Measure
Feasibility of biosensor activity tracking
Outcome Description
Incidence of cardiac-specific adverse events and study intervention-related serious adverse events
Outcome Time Frame
12 months
Outcome Measure
Overall safety of INXN-4001
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ulrich Jorde
Investigator Email
ujorde@montefiore.org
Investigator Phone