Safety and Efficacy Study of Engensis (VM202) in the Treatment of Chronic Non-Healing Foot Ulcers

NCT ID: NCT02563522

Last Updated: 2025-10-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-27
• Study Completion Date: 2019-09-24

Brief Summary

This study will assess the safety and efficacy of using gene therapy via intramuscular injections of the calf for patients with chronic non-healing foot ulcers.

Detailed Description

A phase III, randomized, double-blind, placebo-controlled, multicenter, 7-month study designed to assess the safety and efficacy of intramuscular (IM) injections in the calf of Engensis (VM202) in patients with chronic nonhealing foot ulcers. Three hundred patients will be randomized in a 2:1 ratio of VM202 or placebo injections:

• Active -Engensis (VM202) + standard of care - 200 patients
• Control - Placebo (VM202 Vehicle) + standard of care - 100 patients

Conditions

Foot Ulcer, Diabetic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Active

Engensis (VM202) + standard of care

Group Type: ACTIVE_COMPARATOR

Engensis (VM202)

Intervention Type: GENETIC

gene therapy

Control

Placebo (VM202 Vehicle) + standard of care

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Standard of care plus placebo

Interventions

Engensis (VM202)

gene therapy

Intervention Type: GENETIC

Placebo

Standard of care plus placebo

Intervention Type: DRUG

Other Intervention Names

VM202 vehicle

Eligibility Criteria

Inclusion Criteria

1. Male or female, between 18 and 80 years of age

2. Documented history of symptomatic PAD, with one or more of the following criteria satisfied:

1. ABI >0.40 and ≤0.90 or >1.4 (i.e., mild to severe PAD without critical limb ischemia) in target limb

2. TBI ≤0.7 in the target limb

3. Toe pressure of <55 mmHg in the target limb

4. A history of lower extremity PAD with previous related intervention in a leg

3. Documented history of Type I or II diabetes with current treatment control (HbA1c of ≤12.0% at Screening) and currently on oral medication, injectable medication, and/or insulin

4. No significant changes were anticipated in diabetes medication regimen

5. At Screening, the subject had one ulcer on the target foot that fulfilled all of the following criteria:

1. Present for ≥2 weeks and ≤1 year

2. Full-thickness and not involving bone, tendon, or capsule (probing to tendon or capsule)

3. No sign of infection or osteomyelitis

Exclusion Criteria

6. Capable of understanding and complying with the protocol and signed the informed consent document prior to being subjected to any study related procedures

7. If female of childbearing potential, negative urine pregnancy test at Screening and used an acceptable method of birth control during the study

1. Required revascularization in the target leg within 3 months of randomization

2. In the Investigator's assessment, required an amputation in the target leg within 3 months of randomization

3. Subjects with target foot ulcer with an etiology of vasculitis, pyoderma gangrenosum, necrobiosis lipoidica, hydrostatic pressure/venous insufficiency, any neoplasms (basalioma, Kaposi's sarcoma, squamous cell carcinoma, etc.), or due to a burn

4. The study ulcer increased or decreased by 50% or more at Baseline from Screening (as assessed by comparison of post-debridement photos taken at Screening and Day 0)

5. Evidence of active infection (e.g., cellulitis, osteomyelitis) or deep ulceration exposing bone or tendon in the foot planned for treatment

6. Any gangrene

7. Current fracture in the target foot

8. Target ulcer located on an active (hot) Charcot foot

9. Heart Failure with a New York Heart Association (NYHA) classification of III or IV

10. Body mass index (BMI) >45 kg/m2 at Screening

11. Stroke or myocardial infarction within the last 3 months

12. Unstable angina

13. Uncontrolled hypertension defined as sustained systolic blood pressure (SBP) >200 mmHg or diastolic blood pressure (DBP) >110 mmHg at Baseline/Screening evaluation

14. Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that precluded standard ophthalmologic examination

15. Inflammatory disorder of the blood vessels (inflammatory angiopathy, such as Buerger's disease)

16. Subjects with advanced liver disease including decompensated cirrhosis, jaundice, ascites, or bleeding varices

17. Subjects currently receiving immunosuppressive medications chemotherapy, or radiation therapy

18. Positive human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV) at Screening

19. Active hepatitis B or C infection as determined by hepatitis B surface antibody (HBsAb), hepatitis B core antibody (immunoglobulin G [IgG] and immunoglobulin M [IgM]; HBcAb), hepatitis B surface antigen (HBsAg), and hepatitis C antibodies (Anti-HCV) at Screening

20. Clinically significant specific laboratory values at Screening (e.g., hemoglobin <8.0 g/dL, white blood cell [WBC] <3,000/μL, platelet count <75,000/mm3, aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT] >3 times the upper limit of normal, or any other clinically significant lab abnormality which in the opinion of the Investigator was exclusionary)

21. Glomerular filtration rate (GFR) <30 mL/min/1.73 m2

22. Subjects with a recent history (<5 years) of or new Screening finding of malignant neoplasm except basal cell carcinoma or squamous cell carcinoma of the skin (if excised and no evidence of recurrence for at least 1 year); subjects with medical history and/or family history of colon cancer in any first degree relative were excluded unless they had undergone a colonoscopy in the last 12 months with negative findings

23. Subjects with any comorbid conditions likely to have interfered with assessment of safety or efficacy or with an estimated life expectancy of less than 1 year

24. Subjects who required >81 mg daily of acetylsalicylic acid. If >81 mg was taken at Screening, subjects could be enrolled if they were willing/able to switch to another medication for the duration of the study

25. Subjects who required regular (daily) COX-2 inhibitor drug(s) or steroids (except inhaled steroids or ocular steroids); subjects could be enrolled if they were willing/able to undergo medication washout prior to the first dosing and refrained from taking these drugs during the study

26. Major psychiatric disorder in the past 6 months

27. History of drug or alcohol abuse/dependence in the past 2 years

28. Used an investigational drug in the past 3 months; used an investigational biologic in the past 12 months; concurrent participation in an investigational protocol or using unapproved therapeutics

29. Was unable or unwilling to give informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helixmith Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emerson C. Perin, MD

Role: PRINCIPAL_INVESTIGATOR

Texas Heart Institute

David G Armstrong,, DPM, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Keck School of Medicine of University of Southern California

Locations

Central Research Associates, Inc.

Birmingham, Alabama, United States

Arizona Research Center

Phoenix, Arizona, United States

University of Arizona

Tucson, Arizona, United States

NEA Baptist

Jonesboro, Arkansas, United States

Sacramento Foot and Ankle

Carmichael, California, United States

Bay Area Foot and Ankle

Castro Valley, California, United States

VA Long Beach Healthcare System

Long Beach, California, United States

USC Keck School of Medicine

Los Angeles, California, United States

Foot and Ankle Clinic

Los Angeles, California, United States

Center for Clinical Research Inc.

San Francisco, California, United States

Olive View-UCLA Education & Research Institute

Sylmar, California, United States

LCC Medical Research Institute

Miami, Florida, United States

Miami Dade Medical Research Institute, LLC

Miami, Florida, United States

Northwestern University

Chicago, Illinois, United States

UMASS Memorial Med Center

Worcester, Massachusetts, United States

Saint Louis University

St Louis, Missouri, United States

Advanced Foot & Ankle Center

Las Vegas, Nevada, United States

Oregon Foot and Ankle Center

Eugene, Oregon, United States

MedResearch, Inc

El Paso, Texas, United States

Acclaim Bone & Joint Institute

Fort Worth, Texas, United States

Texas Heart Institute

Houston, Texas, United States

Futuro Clinical Trials

McAllen, Texas, United States

Countries

United States

References

Perin E, Loveland L, Caporusso J, Dove C, Motley T, Sigal F, Vartivarian M, Oliva F, Armstrong DG; VMNHU-003 study group. Gene therapy for diabetic foot ulcers: Interim analysis of a randomised, placebo-controlled phase 3 study of VM202 (ENGENSIS), a plasmid DNA expressing two isoforms of human hepatocyte growth factor. Int Wound J. 2023 Nov;20(9):3531-3539. doi: 10.1111/iwj.14226. Epub 2023 May 25.

Reference Type: BACKGROUND

PMID: 37230802 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

VMNHU-003

Identifier Type: -

Identifier Source: org_study_id