Foot Ulcer, Diabetic
Conditions
Keywords
non healing ulcers, VM202, Diabetic ulcers, foot ulcers, Engensis
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
Interventions
GENETICEngensis (VM202)
gene therapy
DRUGPlacebo
Standard of care plus placebo
Sponsors
Helixmith Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Active: Engensis (VM202) + standard of care - 200 subjects Control: Placebo (VM202 vehicle) + standard of care - 100 subjects
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With a Target Wound Closure by the 4-month Follow-up Visit | Days 0 to Month 4 | Determine the proportion of subjects with a target Wound Closure from baseline to month 4 visit |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Engensis (VM202) + standard of care
Engensis (VM202): gene therapy | 27 |
| Control Placebo (VM202 Vehicle) + standard of care
Placebo: Standard of care plus placebo | 17 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | withdrew consent,, noncompliance, and unable to attend future visits | 1 | 2 |
Baseline characteristics
| Characteristic | Control | Total | Active |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 16 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 28 Participants | 20 Participants |
| Age, Continuous | 61.2 years STANDARD_DEVIATION 10.88 | 58.9 years STANDARD_DEVIATION 11 | 57.5 years STANDARD_DEVIATION 11.05 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 36 Participants | 21 Participants |
| Region of Enrollment United States | 17 participants | 44 participants | 27 participants |
| Sex: Female, Male Female | 5 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male Male | 12 Participants | 32 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 17 |
| other Total, other adverse events | 16 / 27 | 14 / 17 |
| serious Total, serious adverse events | 11 / 27 | 5 / 17 |
Outcome results
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
Time frame: Days 0 to Month 4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Proportion of Subjects With a Target Wound Closure by the 4-month Follow-up Visit | 13 Participants |
| Control | Proportion of Subjects With a Target Wound Closure by the 4-month Follow-up Visit | 5 Participants |
Comparison: The statistical hypotheses were H0: Pt = Pc versus Ha: Pt ≠ Pc, where Pt and Pc are the proportions of subjects with a confirmed target would closure by the 4-month follow-up for Active (Engensis) and Control (Placebo) groups, respectively. The hypothesis testing was a two-sided alpha of 0.05p-value: 0.345595% CI: [-12.37, 45.81]Fisher Exact