Foot Ulcer, DiabeticPhase 3NCT02563522

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

A Phase 3 study testing Engensis (VM202) in people with Foot Ulcer, Diabetic, run by Helixmith Co., Ltd. at 22 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Foot Ulcer, Diabetic
What is being tested?: Engensis (VM202)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 44 participants
Where: 22 sitesUnited States
Study dates: 27 Jun 2017to 24 Sep 2019
Phase: Phase 3
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 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female, between 18 and 80 years of age
Documented history of symptomatic PAD, with one or more of the following criteria satisfied:
ABI >0.40 and ≤0.90 or >1.4 (i.e., mild to severe PAD without critical limb ischemia) in target limb
TBI ≤0.7 in the target limb
Toe pressure of <55 mmHg in the target limb
A history of lower extremity PAD with previous related intervention in a leg

Show all 15Show fewer

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
No significant changes were anticipated in diabetes medication regimen
At Screening, the subject had one ulcer on the target foot that fulfilled all of the following criteria:
Present for ≥2 weeks and ≤1 year
Full-thickness and not involving bone, tendon, or capsule (probing to tendon or capsule)
No sign of infection or osteomyelitis
Ulcer must have been 0.5 cm2 to 15 cm2 as measured at the Screening visit prior to debridement If more than one ulcer was present on the foot, the largest ulcer that fulfilled the inclusion and exclusion criteria was considered the target (index) ulcer for the study. Subjects underwent protocol-defined standardized wound care during Screening (for two weeks or longer). Subjects were considered screen failures and did not receive study injections on Day 0 (Baseline) if the target ulcer did not meet all entry criteria (see above) as well as being confirmed as nonhealing.
Capable of understanding and complying with the protocol and signed the informed consent document prior to being subjected to any study related procedures
If female of childbearing potential, negative urine pregnancy test at Screening and used an acceptable method of birth control during the study

Who cannot join

Required revascularization in the target leg within 3 months of randomization
In the Investigator's assessment, required an amputation in the target leg within 3 months of randomization
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
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)
Evidence of active infection (e.g., cellulitis, osteomyelitis) or deep ulceration exposing bone or tendon in the foot planned for treatment
Any gangrene

Show all 29Show fewer

Current fracture in the target foot
Target ulcer located on an active (hot) Charcot foot
Heart Failure with a New York Heart Association (NYHA) classification of III or IV
Body mass index (BMI) >45 kg/m2 at Screening
Stroke or myocardial infarction within the last 3 months
Unstable angina
Uncontrolled hypertension defined as sustained systolic blood pressure (SBP) >200 mmHg or diastolic blood pressure (DBP) >110 mmHg at Baseline/Screening evaluation
Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that precluded standard ophthalmologic examination
Inflammatory disorder of the blood vessels (inflammatory angiopathy, such as Buerger's disease)
Subjects with advanced liver disease including decompensated cirrhosis, jaundice, ascites, or bleeding varices
Subjects currently receiving immunosuppressive medications chemotherapy, or radiation therapy
Positive human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV) at Screening
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
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)
Glomerular filtration rate (GFR) <30 mL/min/1.73 m2
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
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
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
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
Major psychiatric disorder in the past 6 months
History of drug or alcohol abuse/dependence in the past 2 years
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
Was unable or unwilling to give informed consent

Trial locations and contacts

22 sites in 1 country.

City, postcode or hospital

22 sites in 1 country

United States22 sites

Central Research Associates, Inc.
Birmingham, Alabama, 35205
Sacramento Foot and Ankle
Carmichael, California, 95608
Bay Area Foot and Ankle
Castro Valley, California, 94546
Northwestern University
Chicago, Illinois, 60611
MedResearch, Inc
El Paso, Texas, 79932
Oregon Foot and Ankle Center
Eugene, Oregon, 97401
Acclaim Bone & Joint Institute
Fort Worth, Texas, 76107
Texas Heart Institute
Houston, Texas, 77030
NEA Baptist
Jonesboro, Arkansas, 72401
Advanced Foot & Ankle Center
Las Vegas, Nevada, 89119
VA Long Beach Healthcare System
Long Beach, California, 90822
USC Keck School of Medicine
Los Angeles, California, 90033
Foot and Ankle Clinic
Los Angeles, California, 90057
Futuro Clinical Trials
McAllen, Texas, 78501
LCC Medical Research Institute
Miami, Florida, 33126
Miami Dade Medical Research Institute, LLC
Miami, Florida, 33176
Arizona Research Center
Phoenix, Arizona, 85053
Center for Clinical Research Inc.
San Francisco, California, 94115
Saint Louis University
St Louis, Missouri, 63110
Olive View-UCLA Education & Research Institute
Sylmar, California, 91342
University of Arizona
Tucson, Arizona, 85724
UMASS Memorial Med Center
Worcester, Massachusetts, 01655

Other trials in United States

About this study

Official title: A Phase III, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Safety and Efficacy of VM202 to Treat Chronic Nonhealing Foot Ulcers in Diabetic Patients With Concomitant Peripheral Arterial Disease (PAD)

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.

Read the 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
Being tested: Engensis (VM202), Placebo
Keywords: non healing ulcers, VM202, Diabetic ulcers, foot ulcers, Engensis
Medical subject headings: Diabetic Foot, Foot Ulcer

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Engensis (VM202)Genetic
gene therapy
PlaceboDrug
Also called VM202 vehicle
Standard of care plus placebo

Study groups in NCT02563522
Study group	Role	What they receive
Active	Active comparator	Engensis (VM202) + standard of care Receives: Genetic: Engensis (VM202)
Control	Placebo comparator	Placebo (VM202 Vehicle) + standard of care Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Proportion of Subjects With a Target Wound Closure by the 4-month Follow-up Visit
Determine the proportion of subjects with a target Wound Closure from baseline to month 4 visit
Measured: Days 0 to Month 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Jun 201724 Sep 2019

First posted30 Sep 2015 (estimated)
Study start27 Jun 2017
Primary completion24 Sep 2019
Study completion24 Sep 2019

Why it stopped: Low enrollment

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Foot Ulcer, DiabeticStudies 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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Active: Engensis (VM202) + standard of care - 200 subjects Control: Placebo (VM202 vehicle) + standard of care - 100 subjects
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02563522
Sponsor's protocol ID: VMNHU-003
Status last verified: Aug 2025
First submitted: 28 Sep 2015
Last updated: 9 Oct 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 37230802

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Active, not recruiting
Wearable Insoles for Recurrent Diabetic Ulcer Prevention
Diabetes, Peripheral Neuropathy
Active, not recruiting
Evaluation of Personalized Nutritional Intervention on Wound Healing of Cutaneous Ulcers in Diabetics
Foot, Diabetic
Not yet recruiting
Efficacy Evaluation of Turmeric-Derived Nanoparticle Hydrogel for the Treatment of Diabetic Foot Ulcer Wounds
Diabete Mellitus
Not yet recruiting
Better Care Closer to Home: Enhancing Primary and Community Care
Diabetic Foot Disease, Recurrence

All Foot Ulcer, Diabetic trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Safety and Efficacy of VM202 to Treat Chronic Nonhealing Foot Ulcers in Diabetic Patients With Concomitant Peripheral Arterial Disease (PAD)
ClinicalTrials.gov ID: NCT02563522
Acronym / sponsor ID: VMNHU-003
Conditions: Foot Ulcer, Diabetic
Keywords: non healing ulcers, VM202, Diabetic ulcers, foot ulcers, Engensis
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Low enrollment
Enrolment: 44 participants (actual)
Lead sponsor: Helixmith Co., Ltd.Industry (pharma, biotech, devices)
Study start: 27 Jun 2017 (actual)
Primary completion: 24 Sep 2019 (actual)
Study completion: 24 Sep 2019 (actual)
First posted: 30 Sep 2015 (estimated)
Results: Posted 22 Feb 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2
Model description: Active: Engensis (VM202) + standard of care - 200 subjects Control: Placebo (VM202 vehicle) + standard of care - 100 subjects

Arm	Type	Receives
Active	Active comparator	Genetic: Engensis (VM202)Engensis (VM202) + standard of care
Control	Placebo comparator	Drug: PlaceboPlacebo (VM202 Vehicle) + standard of care

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

Male or female, between 18 and 80 years of age
Documented history of symptomatic PAD, with one or more of the following criteria satisfied:
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
No significant changes were anticipated in diabetes medication regimen
At Screening, the subject had one ulcer on the target foot that fulfilled all of the following criteria:

Key exclusion criteria (29 listed)

Required revascularization in the target leg within 3 months of randomization
In the Investigator's assessment, required an amputation in the target leg within 3 months of randomization
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
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)
Evidence of active infection (e.g., cellulitis, osteomyelitis) or deep ulceration exposing bone or tendon in the foot planned for treatment

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
Engensis (VM202)gene therapy	Genetic	Active
PlaceboAlso: VM202 vehicleStandard of care plus placebo	Drug	Control

Primary outcome

Proportion of Subjects With a Target Wound Closure by the 4-month Follow-up Visit
Time frame: Days 0 to Month 4
Determine the proportion of subjects with a target Wound Closure from baseline to month 4 visit

Results and safety

Results posted to the registry on 22 Feb 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Active	27	23
Control	17	12

Primary outcome: Proportion of Subjects With a Target Wound Closure by the 4-month Follow-up Visit

Time frame: Days 0 to Month 4. Count of participants. Unit: Participants

Measure	Active n = 27	Control n = 17
Value	13	5

Active vs Control: Mean Difference (Final Values): 18.7 (95% CI -12.37 to 45.81), p = 0.3455, Fisher Exact

Adverse events

Time frame: Day 0 to 7 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Active	11 of 27 (40.7%)	16 of 27 (59.3%)	0 of 27
Control	5 of 17 (29.4%)	14 of 17 (82.4%)	0 of 17

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 37230802Perin 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.

Related trials for Foot Ulcer, Diabetic

Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Active, not recruiting
Wearable Insoles for Recurrent Diabetic Ulcer Prevention
Diabetes, Peripheral Neuropathy
Active, not recruiting
Evaluation of Personalized Nutritional Intervention on Wound Healing of Cutaneous Ulcers in Diabetics
Foot, Diabetic
Not yet recruiting
Efficacy Evaluation of Turmeric-Derived Nanoparticle Hydrogel for the Treatment of Diabetic Foot Ulcer Wounds
Diabete Mellitus
Not yet recruiting
Better Care Closer to Home: Enhancing Primary and Community Care
Diabetic Foot Disease, Recurrence

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.

Emerson C. Perin, MD principal investigator

Texas Heart Institute

David G Armstrong,, DPM, MD, PhD principal investigator

Keck School of Medicine of University of Southern California

22 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Engensis (VM202) in people with Foot Ulcer, Diabetic, run by Helixmith Co., Ltd. at 22 sites 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 15 inclusion and 29 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: stopped early, as of the sponsor's last update on 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 Feb 2023). 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?

Proportion of Subjects With a Target Wound Closure by the 4-month Follow-up Visit (time frame: Days 0 to Month 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02563522, which also lists 1 linked publication.

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 9 Oct 2025.