Arterial Occlusive DiseasePhase 2NCT00189540
Study of Hepatocyte Growth Factor (HGF) Via Plasmid Vector to Improve Perfusion in Critical Limb Ischemia Patients With Peripheral Ischemic Ulcers
A Phase 2 study testing HGF plasmid in people with Arterial Occlusive Disease and Peripheral Vascular Disease, run by AnGes USA, Inc. at 4 sites in United States.
Trial summary
The objective of this study is to test the hypothesis that AMG0001 treatment is safe and induces angiogenesis as detected by improved wound healing, reduction in amputation, improved pain at rest and hemodynamic measurement and to assess the effectiveness of the administrative method. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Arterial Occlusive Disease, Peripheral Vascular Disease, Ischemia
- What is being tested?
- HGF plasmid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 4 sitesUnited States
- Study dates
- Aug 2005to Aug 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects will have an appropriately sized peripheral ischemic ulcer(s).
- Subjects will have one or both of the following hemodynamic indicators of severe peripheral arterial occlusive disease:
- Ankle systolic pressure (in either the dorsalis pedis or posterior tibial arteries) of < 70 mmHg
- Toe systolic pressure < 50 mmHg
- The subject is a poor candidate for standard revascularization treatment options for peripheral arterial disease, based on inadequate bypass conduit, unfavorable anatomy, or poor operative risk.
- Subjects 40 years or older of either sex who have signed an informed consent form either directly or through a legally authorized representative.
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- Subjects will be on a statin and an anti-platelet agent (e.g., clopidogrel, ticlopidine, aspirin, etc.) as part of their standard of care, unless contraindicated. Subjects for which these agents are contraindicated will have this restriction recorded in their case report form (CRF). Subjects must be stable on these medical regimens for at least 4 weeks prior to the start of treatment.
- If female, the subjects must be:
- at least one year post-menopausal, or
- surgically sterile, or
- if the subject is of child-bearing potential, she must have been practicing adequate contraception for at least 12 weeks prior to entering the study and have a negative urine pregnancy test result prior to study enrollment and agree to periodic pregnancy screening tests during the study.
- If female, the subject must not be breastfeeding for 30 days following administration of HGF.
- If subject is of reproductive potential, he or she must be using an accepted and effective (barrier) form of birth control during the study.
Who cannot join
- Subjects who, in the opinion of the investigator, have a vascular disease prognosis that indicates they would require a major amputation (at or above the ankle) within 4 weeks of start of treatment.
- Subjects with a diagnosis of Buerger's disease (thromboangiitis obliterans).
- Subjects with hemodynamically significant aorto-iliac occlusive disease.
- Subjects who have had a revascularization procedure within 12 weeks prior to treatment initiation that remains patent. Revascularization procedures that are evidenced to have failed (completely occluded) for >2 weeks prior to treatment initiation are acceptable.
- Subjects who require a change in their hypertension medication (other than dosage change) as part of their standard of care within 4 weeks prior to treatment initiation.
- Subjects with deep ulcerations with bone or tendon exposure, or clinical evidence of invasive infection (e.g., cellulitis, osteomyelitis, etc.) uncontrollable by antibiotics.
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- Subjects currently receiving immuno-suppressive medication, chemo or radiation therapy.
- Evidence or history of malignant neoplasm (clinical, laboratory or imaging), except for fully resolved basal cell carcinoma of the skin. Patient's who had successful tumor resection or radio-chemotherapy of breast cancer more than 10 years prior to inclusion in the study, and with no recurrence, may be enrolled in the study. Patient's who had successful tumor resection or radio-chemotherapy of all other tumor types more than 5 years prior to inclusion in the study, and with no recurrence, may be enrolled in the study.
- Subjects who have proliferative diabetic retinopathy, severe non-proliferative retinopathy, recent (within 6 months) retinal vein occlusion, macular degeneration with choroidal neovascularization, macular edema on fundus evaluation by ophthalmologist, or intraocular surgery within 3 months.
- Subjects with end stage renal disease (ESRD) defined as significant renal dysfunction evidenced by a creatinine of > 2.5 mg/dL, or receiving chronic hemodialysis therapy.
- Any co-morbid condition likely to interfere with assessment of safety or efficacy endpoints, acute cardiovascular events (i.e. cerebrovascular accident [CVA], myocardial infarction [MI], etc.) within 12 weeks of treatment, or non-cardiovascular diseases that in the opinion of the investigator may result in < 3 month subject mortality.
- A subject who has a history of hepatic cirrhosis, viral hepatitis, or HIV.
- Subjects with a clinically significant liver enzyme abnormality (i.e., AST or ALT more than two times the upper limit of normal and/or bilirubin more than 50% above the upper limit of normal).
- Subjects taking cilostazol (Pletal®) are eligible for inclusion, but the subject must have been taking the medication for at least 4 weeks prior to test material administration.
- Subject who received another investigational drug for peripheral arterial disease within 90 days of randomization, have previously received any gene transfer therapy or growth factor product not approved by the United States Food and Drug Administration (FDA) or received any investigational Drug Product in another clinical trial in the 30 days prior to administration of HGF.
- Unreliable or uncooperative subject or other severe concomitant disease(s), which the clinical investigator feels constitute(s) criteria for exclusion of a particular subject.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Boston Medical Center
Boston, Massachusetts, 02118
The Care Group, LLC
Indianapolis, Indiana, 46290
Dartmouth - Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Baptist Clinical Research
Pensacola, Florida, 32501
About this study
Official title: A Phase II Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety and Efficacy of AMG0001 to Improve Perfusion in Critical Limb Ischemia in Subjects Who Have Peripheral Ischemic Ulcers
The objective of this study is to test the hypothesis that AMG0001 treatment is safe and induces angiogenesis as detected by improved wound healing, reduction in amputation, improved pain at rest and hemodynamic measurement and to assess the effectiveness of the administrative method.
Read the detailed description
The primary goals of this study evaluating AMG0001 administration in CLI subjects will be to investigate the efficacy and safety of AMG0001. Specifically, the objectives are:
- Assess efficacy of a dosing regimen of 4.0mg/3 mL AMG0001, administered on Days 0, 14, and 28 as measured by reduction in total wound area at Month 3.
- Assess potential effects of angiogenesis associated with a dosing regimen of 4.0mg/3 mL AMG0001, administered on Days 0, 14, and 28 as measured by reduction in total wound area at Months 6 and 12, along with reduction in major amputations and improved pain at rest as measured on the VAS and hemodynamic measures (ABI/TBI) at Month 3 and Month 6.
- Assess overall safety of AMG0001 in the Critical Limb Ischemia subject population as determined by physical examination, blood and urine analyses, electrocardiogram, vital signs, and by evaluation of adverse experiences during and after the course of treatment.
- Being tested
- HGF plasmid, Placebo
- Keywords
- Ischemic ulcers, Critical Limb Ischemia
- Medical subject headings
- Arterial Occlusive Diseases, Peripheral Vascular Diseases, Ischemia, Ulcer, Chronic Limb-Threatening Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HGF plasmidGenetic
Intramuscular injections into the index leg on days 0, 14, and 28
PlaceboGenetic
Intramuscular injections into the index leg on days 0, 14, and 28
| Study group | Role | What they receive |
|---|---|---|
| Active Group | Active comparator | 4.0 mg AMG0001 via intramuscular injections on days 0, 14, and 28 Receives: Genetic: HGF plasmid |
| Placebo Group | Placebo comparator | Placebo (saline) via intramuscular injections on days 0, 14, and 28 Receives: Genetic: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wound Healing (Change in Total Wound Area of All Ischemic Ulcers)
Wound healing measured by change in mean total wound area of all ischemic ulcers at Month 3 and Month 6
Measured: Baseline, Month 3, Month 6
Secondary outcomes (5)
Percentage of Participants Where All Ulcers Healed
This outcome is a percentage of participants where all of their baseline ulcers healed.
Measured: Month 3 and Month 6
Change in Pain at Rest as Measured on the Visual Analog Scale (VAS)
The mean VAS score where 0 = no pain; 10 = worst possible pain.
Measured: Baseline, Month 3 and Month 6
Number of Subjects Who Undergo a Major Amputation
Measured: Month 3 and Month 6
Change in Hemodynamic Measurements - Mean Change in Ankle Brachial Index (ABI)
Measured: Baseline, Month 3, Month 6
Change in Hemodynamic Measurements - Mean Change in Toe Brachial Index (TBI)
Measured: Baseline, Month 3, Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2005 (estimated)
- Study startAug 2005
- Primary completionJul 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Arterial Occlusive 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- AnGes USA, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Richard Powell, MD, Principal investigator, Dartmouth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00189540
- Sponsor's protocol ID
- AG-CLI-0205
- Status last verified
- Oct 2021
- First submitted
- 12 Sep 2005
- Last updated
- 28 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
Publications
Powell RJ, Goodney P, Mendelsohn FO, Moen EK, Annex BH; HGF-0205 Trial Investigators. Safety and efficacy of patient specific intramuscular injection of HGF plasmid gene therapy on limb perfusion and wound healing in patients with ischemic lower extremity ulceration: results of the HGF-0205 trial. J Vasc Surg. 2010 Dec;52(6):1525-30. doi: 10.1016/j.jvs.2010.07.044.
PubMed 21146749
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety and Efficacy of AMG0001 to Improve Perfusion in Critical Limb Ischemia in Subjects Who Have Peripheral Ischemic Ulcers
- ClinicalTrials.gov ID
- NCT00189540
- Acronym / sponsor ID
- AG-CLI-0205
- Keywords
- Ischemic ulcers, Critical Limb Ischemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- AnGes USA, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2005
- Primary completion
- Jul 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 19 Sep 2005 (estimated)
- Results
- Posted 19 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to test the hypothesis that AMG0001 treatment is safe and induces angiogenesis as detected by improved wound healing, reduction in amputation, improved pain at rest and hemodynamic measurement and to assess the effectiveness of the administrative method.
Detailed description
The primary goals of this study evaluating AMG0001 administration in CLI subjects will be to investigate the efficacy and safety of AMG0001. Specifically, the objectives are:
- Assess efficacy of a dosing regimen of 4.0mg/3 mL AMG0001, administered on Days 0, 14, and 28 as measured by reduction in total wound area at Month 3.
- Assess potential effects of angiogenesis associated with a dosing regimen of 4.0mg/3 mL AMG0001, administered on Days 0, 14, and 28 as measured by reduction in total wound area at Months 6 and 12, along with reduction in major amputations and improved pain at rest as measured on the VAS and hemodynamic measures (ABI/TBI) at Month 3 and Month 6.
- Assess overall safety of AMG0001 in the Critical Limb Ischemia subject population as determined by physical examination, blood and urine analyses, electrocardiogram, vital signs, and by evaluation of adverse experiences during and after the course of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Group | Active comparator | Genetic: HGF plasmid4.0 mg AMG0001 via intramuscular injections on days 0, 14, and 28 |
| Placebo Group | Placebo comparator | Genetic: PlaceboPlacebo (saline) via intramuscular injections on days 0, 14, and 28 |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Subjects will have an appropriately sized peripheral ischemic ulcer(s).
- Subjects will have one or both of the following hemodynamic indicators of severe peripheral arterial occlusive disease:
- The subject is a poor candidate for standard revascularization treatment options for peripheral arterial disease, based on inadequate bypass conduit, unfavorable anatomy, or poor operative risk.
- Subjects 40 years or older of either sex who have signed an informed consent form either directly or through a legally authorized representative.
- Subjects will be on a statin and an anti-platelet agent (e.g., clopidogrel, ticlopidine, aspirin, etc.) as part of their standard of care, unless contraindicated. Subjects for which these agents are contraindicated will have this restriction recorded in their case report form (CRF). Subjects must be stable on these medical regimens for at least 4 weeks prior to the start of treatment.
Key exclusion criteria (16 listed)
- Subjects who, in the opinion of the investigator, have a vascular disease prognosis that indicates they would require a major amputation (at or above the ankle) within 4 weeks of start of treatment.
- Subjects with a diagnosis of Buerger's disease (thromboangiitis obliterans).
- Subjects with hemodynamically significant aorto-iliac occlusive disease.
- Subjects who have had a revascularization procedure within 12 weeks prior to treatment initiation that remains patent. Revascularization procedures that are evidenced to have failed (completely occluded) for >2 weeks prior to treatment initiation are acceptable.
- Subjects who require a change in their hypertension medication (other than dosage change) as part of their standard of care within 4 weeks prior to treatment initiation.
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 |
|---|---|---|
| HGF plasmidIntramuscular injections into the index leg on days 0, 14, and 28 | Genetic | Active Group |
| PlaceboIntramuscular injections into the index leg on days 0, 14, and 28 | Genetic | Placebo Group |
Primary outcome
Wound Healing (Change in Total Wound Area of All Ischemic Ulcers)
Time frame: Baseline, Month 3, Month 6
Wound healing measured by change in mean total wound area of all ischemic ulcers at Month 3 and Month 6
5 secondary outcomes
Percentage of Participants Where All Ulcers Healed
Time frame: Month 3 and Month 6
Change in Pain at Rest as Measured on the Visual Analog Scale (VAS)
Time frame: Baseline, Month 3 and Month 6
Number of Subjects Who Undergo a Major Amputation
Time frame: Month 3 and Month 6
Change in Hemodynamic Measurements - Mean Change in Ankle Brachial Index (ABI)
Time frame: Baseline, Month 3, Month 6
Change in Hemodynamic Measurements - Mean Change in Toe Brachial Index (TBI)
Time frame: Baseline, Month 3, Month 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21146749Powell RJ, Goodney P, Mendelsohn FO, Moen EK, Annex BH; HGF-0205 Trial Investigators. Safety and efficacy of patient specific intramuscular injection of HGF plasmid gene therapy on limb perfusion and wound healing in patients with ischemic lower extremity ulceration: results of the HGF-0205 trial. J Vasc Surg. 2010 Dec;52(6):1525-30. doi: 10.1016/j.jvs.2010.07.044.
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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.
Richard Powell, MD principal investigator
Dartmouth
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HGF plasmid in people with Arterial Occlusive Disease and Peripheral Vascular Disease, run by AnGes USA, Inc. at 4 sites in United States.
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 13 inclusion and 16 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: finished, as of the sponsor's last update on 28 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
Yes. Results are posted in the registry (first posted 19 Aug 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Wound Healing (Change in Total Wound Area of All Ischemic Ulcers) (time frame: Baseline, Month 3, Month 6). 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 NCT00189540, which also lists 1 linked publication.
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 28 Oct 2021.