A Phase I Safety, Dose Escalating Study of MultiGeneAngio in Patients With Peripheral Arterial Disease
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- PAD
- Sponsor
- MultiGene Vascular Systems Ltd.
- Enrollment
- 12
- Locations
- 2
- Primary Endpoint
- The safety of MultiGeneAngio will be assessed by monitoring adverse events
- Status
- Active, not recruiting
- Last Updated
- 11 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and activity of increasing doses of MultiGeneAngio, a cell therapy product produced from the patient's own cells, as potential treatment for patients with peripheral arterial disease.
Detailed Description
Approximately 16 million patients worldwide (1 in 20 people over the age of 50) suffer from peripheral arterial disease(PAD). PAD is characterized by narrowing or occlusion of vessels supplying blood to the lower limbs, most often due to atherosclerosis. Symptoms of PAD include claudication that may progress to critical limb ischemia manifested by rest pain, tissue loss and gangrene, which eventually may necessitate amputation. MultiGeneAngio is a cell therapy-based product developed for treatment of patients with PAD secondary to narrow or blocked arteries in the legs. MultiGeneAngio is composed of endothelial and smooth muscle cells that are isolated from a short vein segment stripped from the patient's arm. After isolation the cells are expanded, characterized, and gene modified by transfer of angiogenic genes. MultiGeneAngio is a clear cell suspension injected intra-arterially at the site of blockage using a standard diagnostic catheter, in order to create and expand new collateral arteries, and thereby improve blood flow to an ischemic limb. Comprehensive pre-clinical studies, as well as clinical experience with PAD patients suffering from claudication showed that production and administration of MultiGeneAngio was feasible and safe, as no apparent drug-related adverse events have been observed. Moreover, follow-up data of peak walking times imply a beneficial trend of this efficacy end-point. Additional follow-up data will continue to be collected to help evaluate the safety and efficacy of MultiGeneAngio.
Investigators
Eligibility Criteria
Inclusion Criteria
- •History of exercise-limiting intermittent claudication and peripheral arterial disease with symptoms in one or both legs, of at least 2 months duration with no change in symptom severity in the 2 months prior to screening.
- •A Doppler-measured ankle-brachial index (ABI) of ≤0.80 or toe-brachial index (TBI) of \<0.70 in at least one leg after 10 minutes of rest.
- •Limitation in walking secondary to claudication with a mean peak walking time (PWT) of between 1 and 10 minutes on a standardized Gardner protocol for exercise treadmill test (ETT).
- •Angiographic or equivalent anatomic evidence (MRA) of arterial occlusive disease (\>70%) in the distal common femoral artery or superficial femoral artery and its branches of at least one leg within 12 months prior to screening.
- •Postmenopausal (females),surgically sterile, or use adequate birth control.
Exclusion Criteria
- •Presence of significant inflow disease \[defined as \>50% stenosis\] in the distal aorta, common or external iliac as assessed by conventional angiogram, digital subtraction angiography (DSA), or magnetic resonance angiography (MRA) performed \< 1 year prior to screening.
- •Critical limb ischemia, either chronic or acute ischemia manifested by rest pain, ulceration, or gangrene (Category 4 through 6 of Society for Vascular Surgery \[SVS\] classification \[Rutherford\]).
- •History of malignant neoplasm (except curable non-melanoma skin malignancies).
- •Renal failure (serum creatinine \>2.0 mg/dL) or end-stage renal disease(requiring hemodialysis or renal replacement therapy).
- •Significant hepatic disease (\>3-fold elevation in ALT/AST).
- •HBV or HCV carriers.
- •Severe pulmonary disease (e.g. severe chronic obstructive pulmonary disease).
- •Subjects with Acute Stroke within 6 months prior to screening.
- •Subjects with uncontrolled diabetes mellitus.
- •Specific ophthalmologic conditions that preclude retinal photography,vascular lesions of the anterior segment of the eye, proliferative retinopathy, age-related macular degeneration or intra-ocular surgery within 6 months prior to enrollment.
Outcomes
Primary Outcomes
The safety of MultiGeneAngio will be assessed by monitoring adverse events
Time Frame: Up to 15 years after treatment
Secondary Outcomes
- Improvement in PAD symptoms(Up to one year after treatment)