Peripheral Arterial DiseasePhase 1/2NCT00956332
Safety Study of MultiGeneAngio in Patients With Chronic Critical Limb Ischemia
A Phase 1/2 study testing MultiGeneAngio in people with Peripheral Arterial Disease and Peripheral Vascular Disease, run by MultiGene Vascular Systems Ltd. at 7 sites in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Peripheral Arterial Disease, Peripheral Vascular Disease, Critical Limb Ischemia
- What is being tested?
- MultiGeneAngio
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 7 sitesIsrael
- Study dates
- Feb 2010to May 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Israel7 sites
Barzilai Medical Center
Ashkelon, 78278
Soroka Medical Center
Beersheba, 84101
Rambam Medical Center
Haifa, 31096
Shaare Zedek Medical Center
Jerusalem, 91031
Hadassah University Hospital, Ein Kerem
Jerusalem, 91120
Kaplan Medical Center
Rehovot, 76100
Chaim Sheba Medical Center
Tel HaShomer, 52621
About this study
Official title: Phase I/IIa Safety, Two-dose Study of MultiGeneAngio in Patients With Chronic Critical Limb Ischemia
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.
Read the 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.
- Being tested
- MultiGeneAngio
- 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
- Medical subject headings
- Peripheral Arterial Disease, Peripheral Vascular Diseases, Chronic Limb-Threatening Ischemia, Diabetic Foot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MultiGeneAngioBiological
Low-therapeutic dose of MultiGeneAngio in suspension administered as one treatment, intra-arterially
MultiGeneAngioBiological
Intermediate-therapeutic dose of MultiGeneAngio in suspension administered as one treatment, intra-arterially
| Study group | Role | What they receive |
|---|---|---|
| MGA - Low therapeutic dose | Experimental | Not described Receives: Biological: MultiGeneAngio |
| MGA - Intermediate therapeutic dose | Experimental | Not described Receives: Biological: MultiGeneAngio |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of MultiGeneAngio will be assessed by monitoring adverse events
Measured: Up to 15 years after treatment
Secondary outcomes (1)
Improvement in critical limb ischemia symptoms
Measured: Up to 3 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2009 (estimated)
- Study startFeb 2010
- Primary completionAug 2011
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- MultiGene Vascular Systems Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sam L. Teichman, MD, Study director, Independent consultant
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00956332
- Sponsor's protocol ID
- MGVS-MGA 002
- Status last verified
- Mar 2015
- First submitted
- 9 Aug 2009
- Last updated
- 5 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 16243400Gray 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.
PubMed 19106409Staudacher 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.
PubMed 17168694Gluzman 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.
PubMed 17544375Tongers 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.
PubMed 18591450Isner 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.
PubMed 11532899
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/IIa Safety, Two-dose Study of MultiGeneAngio in Patients With Chronic Critical Limb Ischemia
- ClinicalTrials.gov ID
- NCT00956332
- Acronym / sponsor ID
- MGVS-MGA 002
- Keywords
- Peripheral arterial disease (PAD), Peripheral vascular disease (PVD), Critical limb ischemia (CLI), Cell therapy, Gene therapy, Endothelial cells, Smooth muscle cells, Angiogenesis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (actual)
- Lead sponsor
- MultiGene Vascular Systems Ltd.Industry (pharma, biotech, devices)
- Study start
- Feb 2010
- Primary completion
- Aug 2011 (actual)
- Study completion
- May 2026 (estimated)
- First posted
- 11 Aug 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MGA - Low therapeutic dose | Experimental | Biological: MultiGeneAngio |
| MGA - Intermediate therapeutic dose | Experimental | Biological: MultiGeneAngio |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MultiGeneAngioLow-therapeutic dose of MultiGeneAngio in suspension administered as one treatment, intra-arterially | Biological | MGA - Low therapeutic dose |
| MultiGeneAngioIntermediate-therapeutic dose of MultiGeneAngio in suspension administered as one treatment, intra-arterially | Biological | MGA - Intermediate therapeutic dose |
Primary outcome
The safety of MultiGeneAngio will be assessed by monitoring adverse events
Time frame: Up to 15 years after treatment
1 secondary outcome
Improvement in critical limb ischemia symptoms
Time frame: Up to 3 months after treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2015.
- Background: PubMed 16243400Staudacher 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.
- Background: PubMed 19106409Gray 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.
- Background: PubMed 17168694Staudacher 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.
- Background: PubMed 17544375Gluzman 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.
- Background: PubMed 18591450Tongers 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.
- Background: PubMed 11532899Isner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sam L. Teichman, MD study director
Independent consultant
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MultiGeneAngio in people with Peripheral Arterial Disease and Peripheral Vascular Disease, run by MultiGene Vascular Systems Ltd. at 7 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The safety of MultiGeneAngio will be assessed by monitoring adverse events (time frame: Up to 15 years after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00956332, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2015.