Cardiovascular Diseases, Heart-Assist Device, Heart Failure
Conditions
Keywords
retrograde coronary sinus infusion, DNA, non-viral, triple effector plasmid, gene therapy, regenerative medicine, non-stem cell
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).
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).
Interventions
BIOLOGICALINXN-4001
Retrograde coronary sinus infusion of triple effector plasmid (INXN-4001)
Sponsors
Intrexon Corporation
Precigen, Inc
Triple-Gene, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate safety and feasibility of INXN-4001 | 6 months | As assessed by incidence of all study intervention-related adverse events occurring up to 6 months post- treatment intervention-related adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wean tolerability following treatment with INXN-4001 | 12 months | Improvement in 6 minute walk duration and distance |
| Quality of Life following treatment with INXN-4001 | 12 months | Change in Kansas City Cardiomyopathy Questionnaire responses |
| Feasibility of biosensor activity tracking | 12 months | Ability to collect daily activity level as measured by wearable biosensor |
| Overall safety of INXN-4001 | 12 months | Incidence of cardiac-specific adverse events and study intervention-related serious adverse events |
Countries
United States
Outcome results
None listed