Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Safety Study of MultiGeneAngio in Patients With Peripheral Arterial Disease (PAD)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
MultiGene Vascular Systems Ltd.
ClinicalTrials.gov Identifier:
NCT00390767
First received: October 19, 2006
Last updated: May 1, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Peripheral Arterial Disease (PAD)
Claudication
Biological: MultiGeneAngio
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Safety, Dose Escalating Study of MultiGeneAngio in Patients With Peripheral Arterial Disease

Resource links provided by NLM:


Further study details as provided by MultiGene Vascular Systems Ltd.:

Primary Outcome Measures:
  • The safety of MultiGeneAngio will be assessed by monitoring adverse events [ Time Frame: Up to 15 years after treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Improvement in PAD symptoms [ Time Frame: Up to one year after treatment ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: October 2006
Estimated Study Completion Date: December 2024
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MultiGeneAngio
Escalating doses of MultiGeneAngio
Biological: MultiGeneAngio
Escalating doses of MultiGeneAngio, one dose per patient administered as one treatment, infused intra-arterially
Other Name: MGA

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.

  Eligibility

Ages Eligible for Study:   50 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  • Gross obesity (BMI≥40).
  • Buerger's disease or other forms of inflammatory arteritis.
  • Class IV congestive heart failure, as defined by the New York Heart Association or a myocardial infarction within 6 months prior to screening.
  • Subject with deep vein thrombosis within 3 months prior to screening.
  • Inability to complete the standardized treadmill protocol for reasons other than claudication including symptoms such as angina, dyspnea, joint pains, or excessive fatigue.
  • Percutaneous intervention or surgical revascularization in the index lower limb within 6 months prior to enrollment.
  • Heart angioplasty with or without stent or coronary bypass surgery within the past 6 months.
  • Participation in a structured exercise treatment protocol within 30 days prior to screen testing.
  • Subject is planning to participate in a structured exercise treatment protocol during the 180 days following administration of the investigational product.
  • Participation in a previous gene transfer trial in which the subject received active investigational product (placebo subjects are eligible).
  • Concurrent or prior participation in another clinical trial within 30 days prior to screen testing.
  • Chronic use of Cox-2 inhibitors, defined as subjects needing daily use of the agent for more than 30 days prior to screening.
  • Subject is taking any of the following drugs for life-threatening conditions or as part of a life-sustaining treatment: Cyclosporine (Sandimmune®),Systemic androgens/anabolic steroids, systemic corticosteroids.
  • History of bleeding diathesis (e.g. hemophilia due to Factor VIII or IX deficiency).
  • Pregnancy or breast-feeding.
  • Uncontrolled hypertension or significant hypotension.
  • Immunodeficiency states (e.g, current HIV positivity, or organ transplant recipient) or subject receiving immunosuppressive medications.
  • Alcohol or other substance abuse.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00390767

Locations
United States, Michigan
University of Michigan and VA Ann Arbor Health Systems
Ann Arbor, Michigan, United States, 48109-0311
United States, Pennsylvania
University of Pennsylvania Health System
Philadelphia, Pennsylvania, United States, 19104-4283
Sponsors and Collaborators
MultiGene Vascular Systems Ltd.
Investigators
Study Director: Sam L Teichman, MD Independent consultant
  More Information

Additional Information:
Publications:
Responsible Party: MultiGene Vascular Systems Ltd.
ClinicalTrials.gov Identifier: NCT00390767     History of Changes
Other Study ID Numbers: MGVS-MGA 001, Protocol #0504-703 (NIH RAC)
Study First Received: October 19, 2006
Last Updated: May 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by MultiGene Vascular Systems Ltd.:
Peripheral arterial disease
Peripheral vascular disease
Claudication
Cell therapy
Gene therapy
Endothelial cells
Smooth muscle cells
Angiogenesis

Additional relevant MeSH terms:
Peripheral Arterial Disease
Peripheral Vascular Diseases
Arterial Occlusive Diseases
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 23, 2014