Novel INXN-4001 Triple Effector Plasmid in Heart Failure

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)

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).

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Heart Failure; Heart-Assist Device
• Intervention / Treatment: Biological: INXN-4001

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).

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Sarver Heart Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Research Center, The Christ Hospital Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Triple-Gene, LLC
• Collaborators: Intrexon Corporation; Precigen, Inc
• Investigators: Principal Investigator: David Bull, MD, University of Arizona; Principal Investigator: Ulrich Jorde, MD, Montefiore Medical Center; Principal Investigator: Gregory Egnaczyk, MD, The Christ Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2018
• Primary Completion (Actual): March 4, 2020
• Study Completion (Actual): August 12, 2020

Study Registration Dates

• First Submitted: November 3, 2017
• First Submitted That Met QC Criteria: January 17, 2018
• First Posted (Actual): January 24, 2018

Study Record Updates

• Last Update Posted (Actual): December 4, 2020
• Last Update Submitted That Met QC Criteria: December 3, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: DNA; gene therapy; regenerative medicine; retrograde coronary sinus infusion; non-viral; triple effector plasmid; non-stem cell
• Additional Relevant MeSH Terms: Heart Diseases; Heart Failure; Cardiovascular Diseases
• Other Study ID Numbers: INXN-4001-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No