Safety and Efficacy Study of Engensis (VM202) in the Treatment of Chronic Non-Healing Foot Ulcers
Condition: Foot Ulcer, Diabetic
MeSH terms: Diabetic Foot; Foot Ulcer; Ulcer
Intervention: Engensis (VM202); Placebo
Intervention description: gene therapy; Standard of care plus placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Active: Engensis (VM202) + standard of care - 200 subjects Control: Placebo (VM202 vehicle) + standard of care - 100 subjects
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: non healing ulcers; VM202; Diabetic ulcers; foot ulcers; Engensis

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.
    

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

               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