Safety Study of MultiGeneAngio in Patients With Chronic Critical Limb Ischemia

NCT00956332 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: MGVS-MGA 002
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Peripheral Arterial Disease; Peripheral Vascular Disease; Critical Limb Ischemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• The safety of MultiGeneAngio will be assessed by monitoring adverse events

  Up to 15 years after treatment

Secondary Outcomes (1)

• Improvement in critical limb ischemia symptoms

  Up to 3 months after treatment

Study Arms (2)

MGA - Low therapeutic dose

EXPERIMENTAL

Biological: MultiGeneAngio

MGA - Intermediate therapeutic dose

EXPERIMENTAL

Biological: MultiGeneAngio

Interventions

MultiGeneAngio BIOLOGICAL

Low-therapeutic dose of MultiGeneAngio in suspension administered as one treatment, intra-arterially

MGA - Low therapeutic dose

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MultiGene Vascular Systems Ltd.: lead

Study Sites (7)

Barzilai Medical Center

Ashkelon, 78278, Israel

Location

Soroka Medical Center

Beersheba, 84101, Israel

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

Hadassah University Hospital, Ein Kerem

Jerusalem, 91120, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Related Publications (6)

• Staudacher DL, Preis M, Lewis BS, Grossman PM, Flugelman MY. Cellular and molecular therapeutic modalities for arterial obstructive syndromes. Pharmacol Ther. 2006 Jan;109(1-2):263-73. doi: 10.1016/j.pharmthera.2005.08.005. Epub 2005 Oct 21.

  PMID: 16243400 BACKGROUND

• Gray BH, Conte MS, Dake MD, Jaff MR, Kandarpa K, Ramee SR, Rundback J, Waksman R; American Heart Association Writing Group 7. Atherosclerotic Peripheral Vascular Disease Symposium II: lower-extremity revascularization: state of the art. Circulation. 2008 Dec 16;118(25):2864-72. doi: 10.1161/CIRCULATIONAHA.108.191177. No abstract available.

  PMID: 19106409 BACKGROUND

• Staudacher DL, Flugelman MY. Cell and gene therapies in cardiovascular disease with special focus on the no option patient. Curr Gene Ther. 2006 Dec;6(6):609-23. doi: 10.2174/156652306779010705.

  PMID: 17168694 BACKGROUND

• Gluzman Z, Koren B, Preis M, Cohen T, Tsaba A, Cosset FL, Shofti R, Lewis BS, Virmani R, Flugelman MY. Endothelial cells are activated by angiopoeitin-1 gene transfer and produce coordinated sprouting in vitro and arteriogenesis in vivo. Biochem Biophys Res Commun. 2007 Jul 27;359(2):263-8. doi: 10.1016/j.bbrc.2007.05.097. Epub 2007 May 25.

  PMID: 17544375 BACKGROUND

• Tongers J, Roncalli JG, Losordo DW. Therapeutic angiogenesis for critical limb ischemia: microvascular therapies coming of age. Circulation. 2008 Jul 1;118(1):9-16. doi: 10.1161/CIRCULATIONAHA.108.784371. No abstract available.

  PMID: 18591450 BACKGROUND

• Isner JM, Vale PR, Symes JF, Losordo DW. Assessment of risks associated with cardiovascular gene therapy in human subjects. Circ Res. 2001 Aug 31;89(5):389-400. doi: 10.1161/hh1701.096259.

  PMID: 11532899 BACKGROUND

MeSH Terms

Conditions

Peripheral Arterial Disease; Peripheral Vascular Diseases; Chronic Limb-Threatening Ischemia; Diabetic Foot

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia; Diabetic Angiopathies; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Study Officials

• Sam L. Teichman, MD

  Independent consultant

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2009
• First Posted: August 11, 2009
• Study Start: February 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: May 1, 2026
• Last Updated: March 5, 2015

Record last verified: 2015-03

Locations

IL (7)