Critical Limb IschemiaPhase 2NCT02016755
A Phase IIB Pilot Study of a Modified Dosage Regimen of AMG0001 in Subjects With Critical Limb Ischemia
A Phase 2 study testing HGF Plasmid in people with Critical Limb Ischemia and Vascular Diseases, run by AnGes USA, Inc. at 1 site in United States.
Trial summary
The purpose of the study is to confirm the feasibility of study procedures and the tolerability of a new dose regimen of AMG0001 in subjects with Critical Limb Ischemia (CLI) Read more about this study
- Who is it for?
- Ages 40 to 90 years
- Conditions the study is for
- Critical Limb Ischemia, Vascular Diseases, Peripheral Arterial Disease
- What is being tested?
- HGF Plasmid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2013to 31 Mar 2018
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with stable CLI (Severe Rutherford 4 and Rutherford 5) who have no option for revascularization by endovascular intervention or surgical bypass or a poor option (high risk) for revascularization by surgery and no option for an endovascular intervention
- Subjects 40-90 years of either gender who have signed an informed consent
- Subjects currently are taking a statin and an anti-platelet agent
- If female, the subjects must not be of child bearing potential, e.g., post-menopausal or surgically sterile.
- If a male subject is of reproductive potential, he must agree to use an accepted and effective (barrier) form of birth control starting with the first dose of study product and continue for 12 weeks from the last dose of study product.
- Subjects with a previous medical history of myocardial infarction and/or stroke should have adequate management of risk factors to prevent secondary occurrence.
- Subjects should have the ability to understand the requirements of the protocol and agree to return for the required study visits and assessments
Who cannot join
- Subjects whose CLI status is unstable (spontaneous marked improvement or marked worsening during the screening period).
- Subjects who may require a major amputation (amputation at or above the ankle) within 4 weeks of Day 0 (± 4 weeks of Day 0).
- Subjects with ulcers with exposure of tendons, osteomyelitis or uncontrolled infection or with the largest ulcer that is greater than 20 cm2 in area (>10 cm2 area if on the heel).
- Subjects with purely neuropathic or venous ulcers.
- Subjects in Rutherford 6 class.
- Subjects who have had revascularization by surgery or angioplasty within 3 months, unless the procedure has failed based on the anatomy or the hemodynamic measurements.
Show all 17Show fewer
- Subjects with a diagnosis of Buerger's disease (Thrombo-angiitis Obliterans).
- Subjects currently receiving immunosuppressive, chemo or radiation therapy.
- Evidence or history of malignant neoplasm (clinical, laboratory or imaging) except for successfully excised basal cell or squamous cell carcinoma, or successfully excised early melanoma of the skin. Subjects, 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. Subjects, who had successful tumor resection or radio-chemotherapy of all other tumor types and have been in remission for more than 5 years prior to inclusion in the study, and with no recurrence, may be enrolled in the study. A dermatological exam will have ruled out any skin cancer.
- Subjects who have proliferative retinopathy, or moderate or severe non-proliferative retinopathy, from any cause (ETDRS Score > 35), clinically significant macular oedema or previous panretinal photocoagulation therapy.
- Subjects with severe renal disease defined as significant renal dysfunction evidenced by an estimated creatinine clearance of <30 mL/minute (calculated using the Cockcroft Gault formula), or receiving chronic hemodialysis therapy.
- A Stroke, TIA or MI within 3 months of entry into the study.
- Subjects with known liver disease (e.g., hepatitis B or C or cirrhosis of the liver).
- A subject with HIV, AIDS, or severe uncontrolled ulcerative colitis or Crohn's disease.
- Subjects with a current, uncorrected history of alcohol or substance abuse.
- Subjects that have been administered rhPDGF (e.g, becaplermin) or other growth factors locally within one month of randomization.
- Subjects who have received another investigational drug within 30 days of randomization or have previously received any gene transfer therapy within 3 years of entering the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
About this study
Official title: A Phase IIB Pilot Study to Confirm the Feasibility and Tolerability of a Modified Dosage Regimen of AMG0001 in Subjects With Critical Limb Ischemia
The purpose of the study is to confirm the feasibility of study procedures and the tolerability of a new dose regimen of AMG0001 in subjects with Critical Limb Ischemia (CLI)
Read the detailed description
The primary objectives of the study are:
- To confirm the feasibility of study-related activities and the tolerability of a modified dosage regimen of AMG0001 in CLI
- To evaluate safety of AMG0001
- Being tested
- HGF Plasmid
- Keywords
- Peripheral Arterial Disease, Vascular Disease, CLI, Critical Limb Ischemia, PAD, AnGes, HGF Plasmid, HGF, Hepatocyte Growth Factor Plasmid, gene therapy
- Medical subject headings
- Chronic Limb-Threatening Ischemia, Vascular Diseases, Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HGF PlasmidBiological
Also called AMG0001
Intramuscular injection in the affected limb.
| Study group | Role | What they receive |
|---|---|---|
| AMG0001 | Experimental | Hepatocyte Growth Factor (HGF) Plasmid Receives: Biological: HGF Plasmid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs) Suspected to be Related to Injections of AMG0001
All summaries and analyses will be presented in tabular or graphical form. The study is not powered for the statistical inference and the test will be considered to be descriptive.
Treatment-emergent adverse events (TEAEs) was evaluated, and a table showing the number and percentage of subjects with occurrences categorized by System Organ Class and Preferred Term was provided by causality (relationship to study drug).
Measured: 18 months
Number of Participants Discontinued Due to AEs From the Injections of AMG0001
All summaries and analyses will be presented in tabular or graphical form. The study is not powered for the statistical inference and the test will be considered to be descriptive.
Treatment-emergent adverse events (TEAEs) was evaluated, and a table showing the number and percentage of subjects with occurrences categorized by System Organ Class and Preferred Term was provided by whether the AE led to discontinuation.
Measured: up to 18 Months
Secondary outcomes (11)
Number of Participants in Whom the Largest Ulcer Healed Completely or Gets Smaller (Photo Confirmation)
All summaries and analyses will be presented in tabular or graphical form. The study is not powered for the statistical inference and the test will be considered to be descriptive.
A table showing the number of subjects completely healed in the target ulcer was provided at up to 6 months, > 6 months to 12 months, from >12 months to 18 months.
Measured: 18 Months
Number of Participants in Whom Rest Pain (Based on 10 cm VAS Scale) Reduces by 20 mm (2 cm) or More or Was Completely Relieved.
All summaries and analyses will be presented in tabular or graphical form. The study is not powered for the statistical inference and the test will be considered to be descriptive.
The severity of rest pain (based on the average over previous 7 days) recorded using the 10 cm visual analog scale (VAS).
VAS is a 10-cm line (with score ranges 0 to 10), oriented horizontally; the left end of the line (0 mark) indicates "no pain"; the right end indicates "pain as bad as it can be."
- The subject is asked to mark a place on the line corresponding to the average pain intensity experienced in the last 7 days.
- The distance along the scale is converted into a numeric reading by measuring the distance of the subjects mark in cm from the beginning of the scale (the 0 mark).
Measured: 18 months
Change From Baseline of VascuQol Score for the Index Limb by Visit
The VascuQol contains 5 domains (pain, symptom, activities, social, and emotional functioning); responses were scored from 0 (lowest QOL, death) to 7 (best QOL, maximum health).
Responses were averaged for composite overall and domain-specific scores, giving equal weight to each question and domain. The composite overall is the average of domain-specific scores.
Responses after revascularization or major amputation were included in the analysis. In the event of death, subjects were scored as 0. For the effect of treatment on individual domains, pain, symptoms, and activities were considered the most important of the 5 domains.
Measured: 18 months
Change in Hemodynamic Measurements of Change From Baseline Value of Toe Systolic Pressure (mmHg)
Summary statistics was provided for baseline and change from baseline for toe systolic pressure by visit. At each visit, only subjects who have a non-missing value at both baseline and the specific visit was summarized. Two-sided one-sample t-test was performed for each visit and last observation carried forward (LOCF).
Measured: 18 months
Change in Hemodynamic Measurements of Change From Baseline Value of Ankle Systolic Pressure (mmHg) of the Index Leg by Visit
Summary statistics was provided for baseline and change from baseline for ankle systolic pressure by visit. At each visit, only subjects who have a non-missing value at both baseline and the specific visit was summarized. Two-sided one-sample t-test was performed for each visit and last observation carried forward (LOCF).
Measured: 18 months
Change in Hemodynamic Measurements of Change From Baseline Value of Brachial Systolic Pressure (mmHg)
Summary statistics was provided for baseline and change from baseline for right/left brachial systolic pressure by visit. At each visit, only subjects who have a non-missing value at both baseline and the specific visit was summarized. Two-sided one-sample t-test was performed for each visit and last observation carried forward (LOCF).
Measured: 18 months
Change in Hemodynamic Measurement of Baseline Calculated Toe Brachial Index (TBI) of the Index Leg by Visit
Summary statistics was provided for baseline and change from baseline for toe brachial index (TBI) by visit. At each visit, only subjects who have a non-missing value at both baseline and the specific visit was summarized. Two-sided one-sample t-test was performed for each visit and last observation carried forward (LOCF).
TBI was calculated by dividing the toe systolic blood pressure by the brachial systolic blood pressure. TBI was calculated at baseline and at each visit. The change in TBI at each visit compared to the baseline value was recorded.
Measured: 18 months
Change in Hemodynamic Measurement of Baseline Calculated ABI of the Index Leg by Visit
Summary statistics was provided for baseline and change from baseline for ankle brachial index (ABI) by visit. At each visit, only subjects who have a non-missing value at both baseline and the specific visit was summarized. Two-sided one-sample t-test was performed for each visit and last observation carried forward (LOCF).
ABI was calculated by dividing the ankle systolic blood pressure by the brachial systolic blood pressure. ABI was calculated at baseline and at each visit. The change in ABI at each visit compared to the baseline value was recorded.
Measured: 18 months
Subjects Who Had Myocardial Infarction (MI), Stroke, Major Amputation, Revascularization (by Surgical Bypass, Endovascular Intervention, Hybrid Procedure), or All-cause Death
A summary table including counts and percentages was provided for subjects who had MI, stroke, major amputation, revascularization, or all-cause death for the time periods: 0 to Month 6, 0 to Month 12, 0 to Month 18.
Measured: 18 months
Number of Participants With Worsening CLI Event of Index Leg
A summary table and listing of worsening CLI-related events of the index leg including any new or worsening events, worsening rest pain, new ulcer or worsening ulcer, new or worsening wound infection, peripheral vascular intervention, complication of a peripheral vascular intervention, cellulitis, and amputation due to worsening CLI was provided.
Measured: 18 months
Number of Participants With Shift From Baseline in Rutherford Classification
Shift from baseline in Rutherford classification was summarized by study visit. Patients enrolled in the study were classified as either Rutherford 4 or Rutherford 5 at baseline.
Rutherford category (clinical description) 0 (Asymptomatic - no hemodynamically significant occlusive disease)
- (Mild claudication)
- (Moderate claudication)
- (Severe claudication)
- (Ischemic rest pain)
- (Minor tissue loss - nonhealing ulcer, focal gangrene with diffuse pedal ischemia)
- (Major tissue loss - extending above TM level, functional foot no longer salvageable)
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2013 (estimated)
- Study startNov 2013
- Primary completion31 Mar 2018
- Study completion31 Mar 2018
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.
- Other trials for Critical Limb IschemiaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 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-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02016755
- Sponsor's protocol ID
- AG-CLI-0209
- Status last verified
- Jan 2021
- First submitted
- 26 Nov 2013
- Last updated
- 22 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIB Pilot Study to Confirm the Feasibility and Tolerability of a Modified Dosage Regimen of AMG0001 in Subjects With Critical Limb Ischemia
- ClinicalTrials.gov ID
- NCT02016755
- Acronym / sponsor ID
- AG-CLI-0209
- Keywords
- Peripheral Arterial Disease, Vascular Disease, CLI, Critical Limb Ischemia, PAD, AnGes, HGF Plasmid, HGF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- AnGes USA, Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2013 (actual)
- Primary completion
- 31 Mar 2018 (actual)
- Study completion
- 31 Mar 2018 (actual)
- First posted
- 20 Dec 2013 (estimated)
- Results
- Posted 22 Jan 2021
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 the study is to confirm the feasibility of study procedures and the tolerability of a new dose regimen of AMG0001 in subjects with Critical Limb Ischemia (CLI)
Detailed description
The primary objectives of the study are:
- To confirm the feasibility of study-related activities and the tolerability of a modified dosage regimen of AMG0001 in CLI
- To evaluate safety of AMG0001
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AMG0001 | Experimental | Biological: HGF PlasmidHepatocyte Growth Factor (HGF) Plasmid |
Who may qualify
- Ages
- 40 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects with stable CLI (Severe Rutherford 4 and Rutherford 5) who have no option for revascularization by endovascular intervention or surgical bypass or a poor option (high risk) for revascularization by surgery and no option for an endovascular intervention
- Subjects 40-90 years of either gender who have signed an informed consent
- Subjects currently are taking a statin and an anti-platelet agent
- If female, the subjects must not be of child bearing potential, e.g., post-menopausal or surgically sterile.
- If a male subject is of reproductive potential, he must agree to use an accepted and effective (barrier) form of birth control starting with the first dose of study product and continue for 12 weeks from the last dose of study product.
Key exclusion criteria (17 listed)
- Subjects whose CLI status is unstable (spontaneous marked improvement or marked worsening during the screening period).
- Subjects who may require a major amputation (amputation at or above the ankle) within 4 weeks of Day 0 (± 4 weeks of Day 0).
- Subjects with ulcers with exposure of tendons, osteomyelitis or uncontrolled infection or with the largest ulcer that is greater than 20 cm2 in area (>10 cm2 area if on the heel).
- Subjects with purely neuropathic or venous ulcers.
- Subjects in Rutherford 6 class.
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 PlasmidAlso: AMG0001Intramuscular injection in the affected limb. | Biological | AMG0001 |
Primary outcome
Number of Participants With Adverse Events (AEs) Suspected to be Related to Injections of AMG0001
Time frame: 18 months
All summaries and analyses will be presented in tabular or graphical form. The study is not powered for the statistical inference and the test will be considered to be descriptive. Treatment-emergent adverse events (TEAEs) was evaluated, and a table showing the number and percentage of subjects with occurrences categorized by System Organ Class and Preferred Term was provided by causality (relationship to study drug).
Number of Participants Discontinued Due to AEs From the Injections of AMG0001
Time frame: up to 18 Months
All summaries and analyses will be presented in tabular or graphical form. The study is not powered for the statistical inference and the test will be considered to be descriptive. Treatment-emergent adverse events (TEAEs) was evaluated, and a table showing the number and percentage of subjects with occurrences categorized by System Organ Class and Preferred Term was provided by whether the AE led to discontinuation.
11 secondary outcomes
Number of Participants in Whom the Largest Ulcer Healed Completely or Gets Smaller (Photo Confirmation)
Time frame: 18 Months
Number of Participants in Whom Rest Pain (Based on 10 cm VAS Scale) Reduces by 20 mm (2 cm) or More or Was Completely Relieved.
Time frame: 18 months
Change From Baseline of VascuQol Score for the Index Limb by Visit
Time frame: 18 months
Change in Hemodynamic Measurements of Change From Baseline Value of Toe Systolic Pressure (mmHg)
Time frame: 18 months
Change in Hemodynamic Measurements of Change From Baseline Value of Ankle Systolic Pressure (mmHg) of the Index Leg by Visit
Time frame: 18 months
Change in Hemodynamic Measurements of Change From Baseline Value of Brachial Systolic Pressure (mmHg)
Time frame: 18 months
Change in Hemodynamic Measurement of Baseline Calculated Toe Brachial Index (TBI) of the Index Leg by Visit
Time frame: 18 months
Change in Hemodynamic Measurement of Baseline Calculated ABI of the Index Leg by Visit
Time frame: 18 months
Subjects Who Had Myocardial Infarction (MI), Stroke, Major Amputation, Revascularization (by Surgical Bypass, Endovascular Intervention, Hybrid Procedure), or All-cause Death
Time frame: 18 months
Number of Participants With Worsening CLI Event of Index Leg
Time frame: 18 months
Number of Participants With Shift From Baseline in Rutherford Classification
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Vessel Recoil in Specific CLTI Populations
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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-Hitchcock Medical Center
1 site 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 Critical Limb Ischemia and Vascular Diseases, run by AnGes USA, Inc. at 1 site 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 7 inclusion and 17 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 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 22 Jan 2021). 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?
Number of Participants With Adverse Events (AEs) Suspected to be Related to Injections of AMG0001 (time frame: 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Jan 2021.