Chronic Limb Threatening Ischemia, Ischaemic Ulcer of Lower Leg Due to Atherosclerotic Disease, Ischemic Ulcer of Foot, Peripheral Artery Disease
Conditions
Brief summary
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
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)
Interventions
BIOLOGICALAMG0001
AMG0001 is a DNA Plasmid encoding hepatocyte growth factor (HGF) administered intramuscularly
BIOLOGICALPlacebo
Matching placebo
Sponsors
AnGes USA, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete ulcer healing at 6 months | Month 6 | Complete ulcer healing defined as skin re-epithelialization without drainage or dressing requirements confirmed at 2 consecutive study visits 2 weeks apart. |
| Time to complete ulcer healing | Month 12 | Complete ulcer healing defined as skin re-epithelialization without drainage or dressing requirements confirmed at 2 consecutive study visits 2 weeks apart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemodynamic measurements of ankle systolic pressure (ASP) | Months 4, 6, 8, 10, 12 | Measure of baseline and change from baseline for hemodynamic parameters |
| Hemodynamic measurements of ankle brachial index (ABI) | Months 4, 6, 8, 10, 12 | Measure of baseline and change from baseline for hemodynamic parameters |
| Hemodynamic measurements of toe brachial index (TBI) | Months 4, 6, 8, 10, 12 | Measure of baseline and change from baseline for hemodynamic parameters |
| The percentage reduction of ulcer size from baseline | Months 4, 6, 8, 10, 12 | — |
| Visual Analogue Scale (VAS) | Months 4, 6, 8, 10, 12 | 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. |
| Occurrence of New Ulcer of the Index leg | Months 4, 6, 8, 10, 12 | Number of subjects and proportions with new ulcer |
| Major / Minor Amputations (digit, forefoot) / Revascularization of the Index Leg | Months 4, 6, 8, 10, 12 | Number of subjects and proportions with major/minor amputation or revascularization |
| Hemodynamic measurements of TcPO2 | Months 4, 6, 8, 10, 12 | Measure of baseline and change from baseline for hemodynamic parameters |
| Hemodynamic measurements of toe pressure (TP) | Months 4, 6, 8, 10, 12 | Measure of baseline and change from baseline for hemodynamic parameters |
Countries
United States
Contacts
Primary ContactMelton Affrime, PharmD
Backup ContactChan Quach
Outcome results
None listed