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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Artery Disease; Chronic Limb Threatening Ischemia; Ischaemic Ulcer of Lower Leg Due to Atherosclerotic Disease; Ischemic Ulcer of Foot
• Intervention / Treatment: Biological: Placebo; Biological: AMG0001

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)

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Melton Affrime, PharmD; Phone Number: +1 908-444-3889; Email: maffrime@anges.co.jp
• Study Contact Backup: Name: Chan Quach; Phone Number: +1 240-780-9033; Email: cquach@anges-usa.com

Study Locations

• United States
  • California
    • Carlsbad, California, United States, 92009
      • Recruiting
      • ILD Research Center
    • Downey, California, United States, 90242
      • Recruiting
      • Rancho Research Institute
    • Fresno, California, United States, 93710
      • Recruiting
      • Limb Preservation Platform, Inc.
    • Los Angeles, California, United States, 90026
      • Recruiting
      • Felix Sigal, D.P.M. A Professional Corporation
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
    • San Francisco, California, United States, 94117
      • Recruiting
      • Center for Clinical Research Inc.
    • Santa Barbara, California, United States, 93111
      • Recruiting
      • Goleta Valley Cottage Hospital
  • Florida
    • Deerfield Beach, Florida, United States, 33442
      • Recruiting
      • BRCR Global
    • South Miami, Florida, United States, 33143
      • Recruiting
      • Doctors Research Network
    • Tamarac, Florida, United States, 33321
      • Recruiting
      • Barry University Clinical Research
    • Winter Park, Florida, United States, 32792
      • Recruiting
      • Guardian Research/Florida Cardiology
  • Illinois
    • Belleville, Illinois, United States, 62226
      • Recruiting
      • Gateway Clinical Trials, LLC
    • North Chicago, Illinois, United States, 60064
      • Recruiting
      • Rosalind Franklin University Health Clinics
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital / Harvard Medical School
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Recruiting
      • Advanced Foot & Ankle Center
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Recruiting
      • Vascular Solutions of North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • The Lindner Center for Research and Education at The Christ Hospital
    • Youngstown, Ohio, United States, 44512
      • Recruiting
      • Lower Extremity Institute for Research and Therapy (LEIRT)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Sciences University
  • Virginia
    • Salem, Virginia, United States, 24153
      • Recruiting
      • Foot and Ankle Associates of Southwest Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMG0001 4mg; AMG0001 4mg + standard wound care	Biological: AMG0001; AMG0001 is a DNA Plasmid encoding hepatocyte growth factor (HGF) administered intramuscularly; Other Names: HGF plasmid; Collategene; beperminogene perplasmid
Experimental: AMG0001 8mg; AMG0001 8mg + standard wound care	Biological: AMG0001; AMG0001 is a DNA Plasmid encoding hepatocyte growth factor (HGF) administered intramuscularly; Other Names: HGF plasmid; Collategene; beperminogene perplasmid
Placebo Comparator: Placebo; Placebo + standard wound care	Biological: Placebo; Matching placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AnGes USA, Inc.
• Investigators: Principal Investigator: David G Armstrong, MD, DPM, PhD, Keck School of Medicine, USC; Principal Investigator: Michael S Conte, MD, Division of Vascular and Endovascular Surgery, UCSF

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2020
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: February 7, 2020
• First Submitted That Met QC Criteria: February 10, 2020
• First Posted (Actual): February 13, 2020

Study Record Updates

• Last Update Posted (Actual): December 22, 2021
• Last Update Submitted That Met QC Criteria: December 21, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Vascular Diseases; Ulcer; Ischemia; Peripheral Arterial Disease
• Other Study ID Numbers: AG-CLTI-0211

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No