Clinical trial NCT03409627: Novel INXN-4001 Triple Effector Plasmid in Heart Failure
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Failure
Cardiovascular Diseases
Heart-Assist Device
Keywords: retrograde coronary sinus infusion
DNA
non-viral
triple effector plasmid
gene therapy
regenerative medicine
non-stem cell
Lead sponsor: Triple-Gene, LLC
Sponsor class: INDUSTRY
Collaborators: name: Intrexon Corporation
name: Precigen, Inc
First posted: 2018-01-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: To evaluate safety and feasibility of INXN-4001
timeFrame: 6 months
Secondary outcomes:
measure: Wean tolerability following treatment with INXN-4001
timeFrame: 12 months
measure: Quality of Life following treatment with INXN-4001
timeFrame: 12 months
measure: Feasibility of biosensor activity tracking
timeFrame: 12 months
measure: Overall safety of INXN-4001
timeFrame: 12 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Sarver Heart Center
state: Arizona
city: Cincinnati
country: United States
facility: The Lindner Research Center, The Christ Hospital Health Network
state: Ohio
Study officials:
affiliation: University of Arizona
name: David Bull, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montefiore Medical Center
name: Ulrich Jorde, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Christ Hospital
name: Gregory Egnaczyk, MD
role: PRINCIPAL_INVESTIGATOR
References: