Novel INXN-4001 Triple Effector Plasmid in Heart Failure

Study Overview
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Brief Summary
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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
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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).

Official Title
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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)

Conditions
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Heart Failure, Cardiovascular Diseases, Heart-Assist Device

Intervention / Treatment
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* Biological: INXN-4001


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Single infusion of INXN-4001, Dose 1 | Biological: INXN-4001<br>* Retrograde coronary sinus infusion of triple effector plasmid (INXN-4001)<br>|
| Experimental: Group 2<br>Single infusion of INXN-4001, Dose 2 | Biological: INXN-4001<br>* Retrograde coronary sinus infusion of triple effector plasmid (INXN-4001)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety and feasibility of INXN-4001 | As assessed by incidence of all study intervention-related adverse events occurring up to 6 months post- treatment intervention-related adverse events | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wean tolerability following treatment with INXN-4001 | Improvement in 6 minute walk duration and distance | 12 months | 
| Quality of Life following treatment with INXN-4001 | Change in Kansas City Cardiomyopathy Questionnaire responses | 12 months | 
| Feasibility of biosensor activity tracking | Ability to collect daily activity level as measured by wearable biosensor | 12 months | 
| Overall safety of INXN-4001 | Incidence of cardiac-specific adverse events and study intervention-related serious adverse events | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DNA, retrograde coronary sinus infusion, non-viral, triple effector plasmid, gene therapy, regenerative medicine, non-stem cell