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

Foot Ulcer, Diabetic Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02563522
• Other study ID #: VMNHU-003
• Status: Terminated
• Phase: Phase 3
• Start date: June 27, 2017
• Est. completion date: September 24, 2019

Study information

• Verified date: January 2023
• Source: Helixmith Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 44
• Est. completion date: September 24, 2019
• Est. primary completion date: September 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

4. 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.

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

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Diabetic Foot
• Foot Ulcer
• Foot Ulcer, Diabetic
• Ulcer

Intervention

Genetic:
• Engensis (VM202)
gene therapy

Drug:
• Placebo
Standard of care plus placebo

Locations

Country	Name	City	State
United States	Central Research Associates, Inc.	Birmingham	Alabama
United States	Sacramento Foot and Ankle	Carmichael	California
United States	Bay Area Foot and Ankle	Castro Valley	California
United States	Northwestern University	Chicago	Illinois
United States	MedResearch, Inc	El Paso	Texas
United States	Oregon Foot and Ankle Center	Eugene	Oregon
United States	Acclaim Bone & Joint Institute	Fort Worth	Texas
United States	Texas Heart Institute	Houston	Texas
United States	NEA Baptist	Jonesboro	Arkansas
United States	Advanced Foot & Ankle Center	Las Vegas	Nevada
United States	VA Long Beach Healthcare System	Long Beach	California
United States	Foot and Ankle Clinic	Los Angeles	California
United States	USC Keck School of Medicine	Los Angeles	California
United States	Futuro Clinical Trials	McAllen	Texas
United States	LCC Medical Research Institute	Miami	Florida
United States	Miami Dade Medical Research Institute, LLC	Miami	Florida
United States	Arizona Research Center	Phoenix	Arizona
United States	Saint Louis University	Saint Louis	Missouri
United States	Center for Clinical Research Inc.	San Francisco	California
United States	Olive View-UCLA Education & Research Institute	Sylmar	California
United States	University of Arizona	Tucson	Arizona
United States	UMASS Memorial Med Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Helixmith Co., Ltd.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Armstrong DG, Perin E, Loveland L, Caporusso J, the VMNHU-003 study group. Gene therapy for diabetic foot ulcers: Interim analysis of a randomized, placebo-controlled phase 3 study of VM202 (ENGENSIS), a plasmid DNA expressing two isoforms of human hepatocyte growth factor (HGF). Diabetic Foot Ulcer Conference 2021 - Poster

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Days 0 to Month 4