Novel INXN-4001 Triple Effector Plasmid in Heart Failure

• ClinicalTrials.gov Identifier: NCT03409627
• Recruitment Status: Active, not recruiting
• First Posted: January 24, 2018
• Last Update Posted: November 18, 2019
• Sponsor: Triple-Gene, LLC
• Collaborators: Intrexon Corporation; Precigen, Inc
• Information provided by (Responsible Party): Triple-Gene, LLC

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Heart Failure; Cardiovascular Diseases; Heart-Assist Device	Biological: INXN-4001	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: April 9, 2018
• Estimated Primary Completion Date: May 20, 2020
• Estimated Study Completion Date: November 20, 2020

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. To evaluate safety and feasibility of INXN-4001 [ Time Frame: 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 Outcome Measures :

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

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Arizona

University of Arizona Sarver Heart Center

Tucson, Arizona, United States, 85724

United States, Ohio

The Lindner Research Center, The Christ Hospital Health Network

Cincinnati, Ohio, United States, 45219

Sponsors and Collaborators

Triple-Gene, LLC

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

More Information

• Responsible Party: Triple-Gene, LLC
• ClinicalTrials.gov Identifier: NCT03409627
• Other Study ID Numbers: INXN-4001-001
• First Posted: January 24, 2018
• Last Update Posted: November 18, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Triple-Gene, LLC:

retrograde coronary sinus infusion; DNA; non-viral; triple effector plasmid; gene therapy; regenerative medicine; non-stem cell

Additional relevant MeSH terms:

Heart Failure; Cardiovascular Diseases; Heart Diseases