Safety Study of MultiGeneAngio in Patients With Chronic Critical Limb Ischemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
MultiGene Vascular Systems Ltd.
ClinicalTrials.gov Identifier:
NCT00956332
First received: August 9, 2009
Last updated: May 1, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to evaluate the safety and activity of two doses of MultiGeneAngio, a cell therapy product produced from the patient's own cells, as potential treatment for patients with chronic critical limb ischemia.


Condition Intervention Phase
Peripheral Arterial Disease
Peripheral Vascular Disease
Chronic Critical Limb Ischemia
Biological: MultiGeneAngio
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/IIa Safety, Two-dose Study of MultiGeneAngio in Patients With Chronic Critical Limb Ischemia

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 critical limb ischemia symptoms [ Time Frame: Up to 3 months after treatment ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: February 2010
Estimated Study Completion Date: May 2026
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MGA - Low therapeutic dose Biological: MultiGeneAngio
Low-therapeutic dose of MultiGeneAngio in suspension administered as one treatment, intra-arterially
Experimental: MGA - Intermediate therapeutic dose Biological: MultiGeneAngio
Intermediate-therapeutic dose of MultiGeneAngio in suspension administered as one treatment, intra-arterially

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 chronic critical limb ischemia due to narrow or blocked leg arteries. MultiGeneAngio is composed of endothelial and smooth muscle cells that are isolated from a short vein segment harvested 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 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women 50 years of age or older
  • Ischemic rest pain (Rutherford category 4) and/or
  • Non-healing wounds (Rutherford category 5)
  • ABI of 0.5 or less, or TBI of 0.3 or less
  • Ankle systolic pressure of 70 mm Hg or less, or toe systolic pressure of 50 mm Hg or less
  • Poor or no option for conventional revascularization

Exclusion Criteria:

  • Life expectancy of less than one year
  • Presence of significant inflow disease (>50% stenosis) in the distal aorta, common or external iliac
  • Advanced CLI, characterized by extensive tissue loss or gangrene (Rutherford category 6)
  • Previous major amputation on the leg to be treated or planned major amputation within a month from enrollment
  • Evidence of osteomyelitis
  • Ischemic wounds with uncontrolled infectious symptoms
  • Heart angioplasty or CABG within 3 months prior to enrollment
  • Severe congestive heart failure (New York Heart Association stage IV)
  • Acute cardiovascular event within 3 months prior to enrollment
  • Uncontrolled blood pressure: SBP≥ 180 mmHg or DBP ≥110 mmHg
  • Known Buerger's disease
  • History of bleeding diathesis (e.g., hemophilia due to Factor VIII or IX deficiency)
  • Renal failure defined as a serum creatinine >2.5mg/dL
  • Significant hepatic disease:>3-fold elevation in ALT/AST, HBV or HCV carriers
  • Severe pulmonary disease
  • Active proliferative retinopathy and/or severe macular oedema
  • Intra-ocular surgery within 6 months prior to enrollment
  • Immunodeficient states (e.g. known HIV positivity, or organ transplant recipient) or subject receiving immunosuppressive medication
  • History of malignant neoplasm (except curable non-melanoma skin malignancies) within 5 years prior to enrollment
  • Pregnant or lactating women
  • Previous treatment with angiogenic growth factors or stem cells
  • No demonstrable venous access
  • Known hypersensitivity to VEGF, Angiopoietin-1, or heparin
  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: NCT00956332

Locations
Israel
Barzilai Medical Center
Ashkelon, Israel, 78278
Soroka Medical Center
Be'er Sheva, Israel, 84101
Rambam Medical Center
Haifa, Israel, 31096
Hadassah University Hospital, Ein Kerem
Jerusalem, Israel, 91120
Shaare Zedek Medical Center
Jerusalem, Israel, 91031
Kaplan Medical Center
Rehovot, Israel, 76100
Chaim Sheba Medical Center
Tel-Hashomer, Israel, 52621
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: NCT00956332     History of Changes
Other Study ID Numbers: MGVS-MGA 002
Study First Received: August 9, 2009
Last Updated: May 1, 2013
Health Authority: United States: Food and Drug Administration
Israel: Ministry of Health

Keywords provided by MultiGene Vascular Systems Ltd.:
Peripheral arterial disease (PAD)
Peripheral vascular disease (PVD)
Critical limb ischemia (CLI)
Cell therapy
Gene therapy
Endothelial cells
Smooth muscle cells
Angiogenesis
Arteriogenesis
amputation
diabetic foot

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

ClinicalTrials.gov processed this record on August 28, 2014