The purpose of this study is to determine the safety, tolerability and preliminary efficacy
of intramuscular injections of VM202 for subjects with critical limb ischemia.
Subjects selected for this study will have critical limb ischemia that has not responded to
standard therapy with symptoms including pain at rest and/or ischemic ulcers.
The study will consist of four (4) cohorts with a total of 3 subjects enrolled in each
cohort to VM202.For each dose cohort, VM202 will be administered as a local intramuscular
injection in 2 divided doses with a 2-week interval between the injections. Preliminary
efficacy (hemodynamic assessments), safety and tolerability will be evaluated at Baseline
(screening) and at designated time points throughout the study.
After all subjects in the first dose cohort have completed the 30-day (+ 2 days) follow-up
visit following the first dose of the study drug, an interim safety evaluation will be
performed with the submission of safety data to the Data Safety Monitoring Committee (DSMC).
If the DSMC recommends continuing the study, the second dose cohort will be treated. This
process will be repeated between the second and third dose cohort and between the third and
fourth dose cohort.
All four dose cohorts will be followed for up to 5 years from the time of the first dose of
study drug administration.
- Male or female, between 20 and 90 years of age
- Have critical limb ischemia (Rutherford Class 4 and 5) and considered not a candidate
for bypass graft surgery or percutaneous angioplasty due to comorbid conditions,
failure of previous surgical or interventional procedures or caliber of grafting
arteries. Critical Limb ischemia is defined as
1. Stable symptoms on standard therapy including anti-platelet agents, vascular
rheologic agents, cilostazol, anticoagulant and pain medication for 30 days.
2. Pain at rest and/or ischemic ulcers for a minimum of 4 weeks.
- Have diagnostic angiography of the affected limb in the last 12 months demonstrating
a significant occlusion of one more of the following arteries: iliac, superficial
femoral, popliteal, and one or more infra-popliteal arteries.
- Have a resting ankle systolic pressure (in either the dorsalis pedis or posterior
tibial arteries) of less than or equal to 60mmHg or a resting toe systolic pressure
of less than or equal to 40 mmHg in the affected limb.
- Be willing to maintain current drug therapy for peripheral arterial disease
throughout the course of the study including anti-platelet and statin (CoA Reductase)
- Be capable of understanding and complying with the protocol and signing the informed
consent document prior to being subjected to any study related procedures
- Women who are surgically sterile or at least 1 year postmenopausal or who have been
practicing adequate contraception for at least 12 weeks prior to entering the study.
If the subject is of child-bearing potential, she must have a negative serum
pregnancy test result during the study.
- If the subject or the subject's partner(s) is of child bearing potential, the subject
and the subject's partner(s) must agree to use a "double barrier" method of birth
control while participating in this study.
- Subjects who have undergone a revascularization procedure or sympathectomy within 12
weeks prior to study entry that remains patent. A failed revascularization procedure
in the previous 4 weeks is acceptable.
- Subjects with grade 3 (hemorrhages, exudates) or grade 4 (papilledema) retinopathy.
- Subjects currently receiving immunosuppressive medications, chemotherapy, radiation
- Subject with aorto-iliac occlusion (greater than 75%).
- Subjects that will require amputation within 4 weeks of randomization.
- Subjects with any co-morbid conditions likely to interfere with assessment of safety
or efficacy or with an estimated life expectancy of less than 6 months
- Subjects with history of drug (defined as illicit drug use) or a history of alcohol
abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per
day) within the past 3 months.
- Subjects with a current history or new screening finding of malignant neoplasm except
for basal cell carcinoma of the skin and squamous cell carcinoma of the skin (if
excised and no evidence of recurrence).
- Subjects with evidence of active infection (e.g. cellulitis, osteomyelitis) or deep
ulceration exposing bone or tendon in the extremity planned for treatment.
- Subjects with a clinically significant abnormality in routine hematology, urinalysis,
chemistry, liver function or other laboratory tests, including HIV, Hepatitis B
(HepBSAg), Cytomegalovirus (CMV), hepatitis C virus (HCV), Venereal Disease Research
Laboratory test (VDRL), prostate-specific antigen (PSA), and chorio-embryonic antigen
(CEA), or signs of malignant neoplasm by radiological imaging tests, including chest
radiograph at Screening or Day 1. Specific laboratory exclusion criteria include the
1. Hemoglobin less than 9.0 G/dl
2. WBC count less than 3,000
3. Platelet count less than 75,000
4. Fasting glucose greater than 250 mg/dl
5. AST and/or ALT greater than 3X upper limit of normal
- Subjects with any other condition that in the opinion of the investigator might put
the subject at risk or interfere with his/her participation.
- Subjects unable or unwilling to comply with the protocol or to cooperate fully with
the investigator or site personnel.
- Subjects that have received any other investigational drug within the 30 days prior
to study drug administration or will receive such a drug during the timeframe of this
- Subjects with uncontrolled hypertension defined as systolic blood pressure greater
than 200 mmHg or diastolic blood pressure greater than 115 mmHg at Baseline
- Subjects with advanced liver disease including decompensated cirrhosis, jaundice,
ascites or bleeding varices.