A Phase I, Open-Label, Non-Randomized, Dose Escalation, Multi Center Study to Assess the Safety and Cardiovascular Effects of Autologous Skeletal Myoblast Implantation by a Transendocardial Catheter Delivery System in Congestive Heart Failure Patients Post Myocardial Infarction(s) With Previous Placement of ICD
MYOHEART™ (Myogenesis Heart Efficiency and Regeneration Trial)
Sponsors
Source
Bioheart, Inc.
Brief Summary
The MyoCell™ implantation using the MyoCath™ delivery catheter system may have the potential
to add a new dimension to the management of post-infarct deterioration of cardiac function in
subjects with congestive heart failure. Based on pre-clinical studies, implantation of
autologous skeletal myoblasts may lead to replacement of non-functioning myocardial scar with
functioning muscle and improvement in myocardial performance. Preliminary data in human
subjects suggest skeletal myoblast implantation at the time of CABG may lead to the same
effects. In principal, myoblast implantation by catheter delivery may offer the same
therapeutic benefit. The present clinical study is to be conducted primarily to evaluate the
safety of MyoCell™ implantation using the MyoCath™ delivery system and secondarily to
evaluate the effect on regional myocardial function post treatment.
Detailed Description
A very promising approach to reversal or stabilization of the post-infarct remodeling process
is the direct injection of regenerative cells into the myocardial infarct scar. Such
cell-based therapy for cardiac repair is called "cellular cardiomyoplasty".
The MyoCell™ implantation using the MyoCath™ delivery catheter system may have the potential
to add a new dimension to the management of post-infarct deterioration of cardiac function in
subjects with congestive heart failure. MyoCath™ is Bioheart's proprietary catheter delivery
system being developed by Bioheart to facilitate MyoCell™ delivery into the myocardium via
the retrograde catheterization of the left ventricular cavity. Based on pre-clinical studies,
implantation of autologous skeletal myoblasts may lead to replacement of non-functioning
myocardial scar with functioning muscle and improvement in myocardial performance.
Preliminary data in human subjects suggest skeletal myoblast implantation at the time of CABG
or via the endoventricular approach may lead to the same effects. In principle, myoblast
implantation by catheter delivery may offer the same therapeutic benefit.
The present clinical study is to be conducted primarily to:
1. Assess the safety and effect on myocardial function of MyoCell™ (autologous skeletal
myoblast) using a dose escalation methodology following implantation into myocardial
scar tissue of subjects with congestive heart failure who have experienced previous
myocardial infarction(s) and have had an implantable cardioverter defibrillator (ICD)
previously implanted. Safety endpoints will be the evaluation of the nature and
frequency of Adverse Events during the 12-month period following MyoCell™ treatment.
2. To assess the safety and feasibility of using the transendocardial injection catheter
(MyoCath™) as a system for delivering MyoCell™ into myocardial scar tissue of subjects
with congestive heart failure who have experienced previous myocardial infarction(s) and
have an implantable cardioverter defibrillator (ICD) previously implanted. Catheter
performance will be assessed at the time of the implantation using clinical evaluation
questionnaires. Safety endpoints will be the evaluation of the nature and frequency of
Adverse Events from the time of implantation to the Day 14 follow-up visit.
If a patient meets the baseline enrollment criteria, approximately 5-10 grams of skeletal
muscle is obtained from the subject's leg muscle for myoblast isolation and expansion in
vitro (MyoCell™) at a specified off site cGMP culture laboratory. The expanded myoblast
cells, MyoCell™ will be implanted into the akinetic myocardial scar in the region of a
previous infarct utilizing Bioheart's MyoCath™ transendocardial delivery catheter system. The
MyoCath™ endoventricular device is expected to deliver the MyoCell™ autologous skeletal
myoblast cells into the scarred myocardial region by steering a catheter which contains a
retractable hypodermic needle to the targeted sites for implantation.
This will be a dose escalation study with 4 cohort groups consisting of 5 patients each. A
report of the 1 month safety data from each cohort will be presented to the Data Safety
Monitoring Board for permission to go to the next higher dosage. In the first cohort of this
dose escalation study, 2 injections will be performed; for the second cohort, 6 injections;
for the third cohort, 18 injections; and for the fourth cohort, 27 injections, depending on
the size of the infarct scar, so as to inject the entire myocardial infarct scar akinetic
area.
The entire study is expected to be completed during the first half of 2007, including
completed enrollment as well as 12-month follow-up of the last subject.
Overall Status
Unknown status
Start Date
2003-02-01
Completion Date
2007-10-01
Primary Completion Date
N/A
Phase
Phase 1
Study Type
Interventional
Primary Outcome
Measure |
To assess the safety of Myocel following implantation into myocardial scar tissue of subjects with congestive heart failure who have experienced previous MI. |
Enrollment
20
Conditions
Intervention
Eligibility
Criteria
Patients who meet all of the following inclusion criteria and none of the exclusion
criteria will be enrolled in this clinical study.
Inclusion Criteria:
- Defined region of myocardial dysfunction related to previous myocardial infarction(s)
involving the anterior, lateral, posterior or inferior walls, > 12 weeks (84 days) old
at the scheduled time of MyoCell™ implantation
- Patients who have had prior placement of an Implantable Cardioverter Defibrillator
(ICD) which must be in place at least one month (30 days) prior to MyoCell™
implantation
- New York Heart Association (NYHA) Symptom Class II or III on optimal medical therapy
- Age > 30 and < 80 years old
- Need for revascularization has been ruled out by coronary angiogram or noninvasive
stress testing within six months (180 days) of screening
- Able to undergo surgical biopsy of the skeletal muscle and successful culture of the
harvested myoblasts Target region wall thickness > 6 mm by Echocardiography
- Left ventricular ejection fraction > 20% and < 40% by Radionuclide Ventriculography or
Left Ventricular Angiography at screening
- Able to give written informed consent
- Able to walk a minimum distance of 300 meters during the 6-minute walk test
Exclusion Criteria:
- Myocardial infarction within 12 weeks (84 days) prior to investigational procedure
- New York Heart Association Symptom Class I or IV
- Coronary Artery Bypass Grafting (CABG) within 3 months (90 days) prior to scheduled
MyoCell™ implantation
- Percutaneous Coronary Intervention (PCI) within 6 months (180 days) prior to MyoCell™
implantation
- Canadian Heart Classification of angina > Class II or unstable angina
- Any cardiac valve replacement
- Heart failure secondary to valvular disease
- Aortic stenosis greater than mild degree
- Left ventricular or atrial mural thrombus
- Chronic pulmonary disease
- Atherosclerosis and/or tortuosity of the aorta, iliac or femoral arteries of a degree
which, in the judgment of the principal investigator, would impede or preclude the
safe retrograde passage of the 8FR MyoCath™ delivery catheter
- History of severe radiocontrast reaction
- Known sensitivity to gentamicin sulfate and/or amphotericin-B
- Previous angiogenic therapy and/or myocardial laser therapy
- Exposure to any investigational drug or procedure within 1 month prior to study entry
- The use or expected use of antineoplastic drugs or history of cancer within 5 years,
except for basal cell carcinoma of the skin
- Skeletal muscle disease, either primary (i.e., myopathy) or secondary (i.e., ischemic)
or any underlying myopathy such as myasthenia gravis, muscular dystrophy, etc. as
determined by a board certified pathologist examining sample of patients muscle biopsy
- Serum creatinine > 2.5 mg/dL or end stage renal disease
- Prostate Specific Antigen (PSA) suggestive of carcinoma of the prostate (i.e., > 4.0
ng/mL)
- Carcinoembryonic Antigen (CEA) >5.0 ng/mL or end stage renal disease
- Active infectious disease and/or who are known to have tested positive for HIV, HTLV,
HBV-sAg, HCV, CMV and/or syphilis. If the panel includes antibodies to the HBc and
HBV-sAg, then an expert will be consulted as to patient eligibility based on the
patient's infectious status
- Females who are pregnant or nursing
- Females of childbearing potential who are unwilling to maintain contraceptive therapy
for the duration of the study
- Morbid obesity - more than 100 pounds over ideal body weight or Body Mass Index (BMI)
> 40
- Any illness which might affect patient's survival over the study 12 month follow-up
period*
- Any illness which, in the Investigator's judgment, will interfere with the patient's
ability to comply with the protocol, compromise patient safety, or interfere with the
interpretation of the study results
- No written Informed Consent or unable to provide informed consent
Gender
All
Minimum Age
30 Years
Maximum Age
80 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
Warren Sherman, MD |
Principal Investigator |
Columbia University |
Timothy Henry, MD |
Principal Investigator |
Minneapolis Heart / Abbott Northwestern |
Nicolas Chronos, MD |
Principal Investigator |
St. Joseph Hospital / ACRI |
Steven Elliss, MD |
Principal Investigator |
The Cleveland Clinic |
David Holmes, MD |
Principal Investigator |
Mayo Clinic |
Location
Facility |
SPONSOR: Bioheart, Inc Sunrise Florida 33325 United States |
American CardioVascular Research Institute Atlanta Georgia 30342 United States |
Minneapolis Heart Institute / Abbot Northwestern Minneapolis Minnesota 55407 United States |
Mayo Clinic Rochester Rochester Minnesota 55905 United States |
Cleveland Clinic Heart Center Cleveland Ohio 44195 United States |
Location Countries
Country
United States
Verification Date
2007-10-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
Version G
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
February 6, 2003
Study First Submitted Qc
February 6, 2003
Study First Posted
February 7, 2003
Last Update Submitted
October 11, 2007
Last Update Submitted Qc
October 11, 2007
Last Update Posted
October 15, 2007
Last Known Status
Active, not recruiting
ClinicalTrials.gov processed this data on December 13, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.