Study of AMG0001 to Improve Ulcer Healing and Perfusion in Subjects With Peripheral Ischemic Ulcers

Study Overview
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Brief Summary
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This study will assess the safety and efficacy of intramuscular injection of AMG0001 (hepatocyte growth factor [HGF] plasmid) to improve ulcer healing and perfusion in patients with peripheral artery disease.

Detailed Description
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This is a Phase 2, double-blind, randomized, placebo-controlled, parallel group study. Approximately 60 male or female subjects aged 18 years or older with one shallow foot ulcer and mild/moderate ischemia due to peripheral artery disease (PAD) will be randomized in a 1:1:1 ratio to one of 3 treatment groups: 4.0 mg AMG0001 intramuscular (IM) (n = 20) 8.0 mg AMG0001 IM (n = 20) Placebo IM (n = 20)

Official Title
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A Phase II Double-Blind, Randomized, Placebo-Controlled Study to Assess the Efficacy and Safety of AMG0001 to Improve Ulcer Healing and Perfusion in Subjects Who Have Peripheral Ischemic Ulcers of the Lower Extremity

Conditions
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Peripheral Artery Disease, Ischaemic Ulcer of Lower Leg Due to Atherosclerotic Disease, Chronic Limb Threatening Ischemia, Ischemic Ulcer of Foot

Intervention / Treatment
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* Biological: AMG0001
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of PAD and mild/moderate foot ischemia (WIFI ischemia grades 1, 2) A single measurable ulcer of ≥ 1 cm2 and ≤ 10 cm2 on a lower extremity without evidence of infection or gangrene and no evidence of bone and/or tendon involvement at randomization Subjects will undergo protocol-defined standardized wound care during the screening period and through 12 months from the first dose of investigational product Subjects who have a diagnosis of diabetes must be considered stable with no changes in diabetic medication regimen anticipated during the study period. Subjects who have a diagnosis of diabetes must have a HbA1c of ≤12% at Screening Exclusion Criteria: Subjects who have excessive tissue necrosis that is unlikely to benefit from medication, or those subjects who, in the opinion of the Investigator, are felt likely to require revascularization within 1 month of screening Subjects with severe limb ischemia Subjects who are considered likely to require a major amputation (at or above the ankle) within 3 months of screening Subjects with deep ulcerations with bone or tendon exposure, or uncontrolled infection, or with the largest ulcer that is >10 cm2 in area Subjects with hemodynamically significant aorto-iliac occlusive disease Subjects who have had a technically successful revascularization by surgery or angioplasty within 2 months. If subjects are more than two months from revascularization and still meet the inclusion criteria, they may be considered for enrollment. Subjects who have had a technically unsuccessful attempt at revascularization may be enrolled at least one week from the procedure Subjects currently receiving immunosuppressive medication, systematically administered steroid therapy, chemotherapy or radiation therapy. Inhaled and topical steroid therapies are allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG0001 4mg<br>AMG0001 4mg + standard wound care | Biological: AMG0001<br>* AMG0001 is a DNA Plasmid encoding hepatocyte growth factor (HGF) administered intramuscularly<br>* Other names: beperminogene perplasmid;|
| Experimental: AMG0001 8mg<br>AMG0001 8mg + standard wound care | Biological: AMG0001<br>* AMG0001 is a DNA Plasmid encoding hepatocyte growth factor (HGF) administered intramuscularly<br>* Other names: beperminogene perplasmid;|
| Placebo Comparator: Placebo<br>Placebo + standard wound care | Biological: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete ulcer healing at 6 months | Complete ulcer healing defined as skin re-epithelialization without drainage or dressing requirements confirmed at 2 consecutive study visits 2 weeks apart. | Month 6 | 
| Time to complete ulcer healing | Complete ulcer healing defined as skin re-epithelialization without drainage or dressing requirements confirmed at 2 consecutive study visits 2 weeks apart. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage reduction of ulcer size from baseline |  | Months 4, 6, 8, 10, 12 | 
| Hemodynamic measurements of toe pressure (TP) | Measure of baseline and change from baseline for hemodynamic parameters | Months 4, 6, 8, 10, 12 | 
| Hemodynamic measurements of ankle systolic pressure (ASP) | Measure of baseline and change from baseline for hemodynamic parameters | Months 4, 6, 8, 10, 12 | 
| Hemodynamic measurements of ankle brachial index (ABI) | Measure of baseline and change from baseline for hemodynamic parameters | Months 4, 6, 8, 10, 12 | 
| Hemodynamic measurements of toe brachial index (TBI) | Measure of baseline and change from baseline for hemodynamic parameters | Months 4, 6, 8, 10, 12 | 
| Hemodynamic measurements of TcPO2 | Measure of baseline and change from baseline for hemodynamic parameters | Months 4, 6, 8, 10, 12 | 
| Visual Analogue Scale (VAS) | Measure of baseline and change from baseline for 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. | Months 4, 6, 8, 10, 12 | 
| Occurrence of New Ulcer of the Index leg | Number of subjects and proportions with new ulcer | Months 4, 6, 8, 10, 12 | 
| Major / Minor Amputations (digit, forefoot) / Revascularization of the Index Leg | Number of subjects and proportions with major/minor amputation or revascularization | Months 4, 6, 8, 10, 12 |