A Randomized, Placebo Controlled, Evaluator-Blinded Study to Assess the Efficacy and Safety of NOX1416 in the Treatment of Chronic, Non-Healing, Diabetic Foot Ulcers
Overview
- Phase
- Phase 1
- Intervention
- NOX-1416+SOC
- Conditions
- Diabetic Foot Ulcer
- Sponsor
- NOxy Health Products, LLC
- Enrollment
- 30
- Locations
- 6
- Primary Endpoint
- Proportion of subjects with complete wound closure during the 12 weeks of the Treatment Phase
- Status
- Suspended
- Last Updated
- 2 years ago
Overview
Brief Summary
The goal of this multi-center,randomized, placebo controlled, evaluator-blinded study is to assess the efficacy and safety of NOX1416 in the treatment of chronic, non-healing, diabetic foot ulcers (DFUs). Subjects will be randomized to receive treatment with NOX1416 or placebo as an adjunct to SOC.
The primary objective of the study is to evaluate the clinical benefit of daily NOX1416, as an adjunct to standard of care (SOC), in the treatment of chronic, non-healing DFUs. The secondary objective is to demonstrate efficacy, safety and tolerability of NOX1416 as adjunct to SOC. Each site will assign a physician (or designee) to serve as the "blinded-evaluator" to be responsible for assessing the study endpoints such as wound measurements and complete wound closure. The blinded-evaluator will not be involved in the clinical care of the subject.
Detailed Description
A total of 30 subjects will be randomized 1:1 to receive either NOX1416 + SOC or Placebo + SOC. NOX1416 is a foam based gaseous nitric oxide (NO) product where NO is delivered through a microbubble foam. One pump each of Solution A (0.3g, containing Citric acid) and Solution B (0.3g, containing Sodium nitrite) will be dispensed, mixed for five seconds and applied immediately per each square centimeter of wound area using any sterile applicator. NOX1416 is topically applied directly onto the wound bed and left on the wound bed for a 5-minute period. Subjects randomized to the NOX1416 treatment group will receive once a day application, for a total of 12 weeks with a double treatment, 10 minutes apart, on the first day. Similar to the NOX1416 treatment schedule, placebo will be topically applied directly onto the wound bed and left on the wound bed for a 5-minute period. Subjects randomized to the control group will receive once a day application, for a total of 12 weeks with a double treatment, 10 minutes apart, on the first day. Standard of care will include evaluation to document, off-loading adequate arterial flow, wound cleaning, removal of necrotic, infected and/or nonviable tissue by debridement, maintenance of moist wound environment, and management of infection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects will be eligible for enrollment in the study only if they meet ALL the following criteria at time of Screening:
- •Male or female subjects aged 18 to 80 years (inclusive) with Type 1 or Type 2 diabetes undergoing therapy for glycemic control.
- •Subject has a glycosylated hemoglobin, HbA1c ≤ 12%. Note: Prior documented HbA1c within the last 3 months of the Screening Visit is acceptable.
- •Presence of at least one diabetic foot ulcer that meets all of the following criteria:
- •A full-thickness ulcer of University of Texas Wound Classification (UTWCS) Grade I or II
- •Ulcer is located on or below the malleoli
- •Ulcer size (area) is ≥ 1 cm2 and ≤ 10 cm2 (post-debridement at time of randomization)
- •Unresponsive to standard ulcer care and present for ≥1 month and ≤1 year (at time of screening)
- •There is a minimum 1 cm margin between the qualifying Target Ulcer and any other ulcers on the specified foot, post-debridement)
- •No exposed bone and no tunneling, undermining, or sinus tracts
Exclusion Criteria
- •Subjects meeting ANY of the following criteria at time of Screening will be excluded from enrollment:
- •Ulcers with exposed bone or associated with osteomyelitis. Note: Osteomyelitis should be ruled out by clinical examination (probing of the wound) or X-ray findings, if necessary, by the Investigator.
- •Subject has ulcers secondary to a disease other than diabetes, e.g., fungal ulcerations, malignant ulcerations, and ulcerations due to venous or arterial insufficiency, or due to hematological disorders, in the opinion of the Principal Investigator.
- •Ulcer, which in the opinion of the Investigator is suspicious for cancer. Note: Ulcers present for \> 6 months would require biopsy to be performed to rule out malignancy.
- •Subjects with a gangrenous or ischemic toe that may need to be amputated in the opinion of the Investigator.
- •Body mass index (BMI) \> 40kg/m2
- •Laboratory values at Screening of:
- •Hemoglobin \< 8.5 g/dL
- •White Blood Cells (WBC) \< 3.0 X 109 cells/L and \> 11 x 109 cells/L
- •Liver function studies \[Total bilirubin, aspartate aminotransferase (AST) and alanine transaminase (ALT)\] \> 3x the upper limit of normal
Arms & Interventions
NOX1416+SOC
NOX1416 is a foam based gaseous nitric oxide (NO) product that will be topically applied directly onto the wound bed and left on the wound bed for a 5-minute period. Subjects randomized to the NOX1416 treatment group will receive once a day application, for a total of 12 weeks with a double treatment, 10 minutes apart, on the first day. Standard of care will include evaluation to document, off-loading adequate arterial flow, wound cleaning, removal of necrotic, infected and/or nonviable tissue by debridement, maintenance of moist wound environment, and management of infection.
Intervention: NOX-1416+SOC
Placebo+SOC
Placebo is topically applied directly onto the wound bed and left on the wound bed for a 5-minute period. Subjects randomized to the control group will receive once a day application, for a total of 12 weeks with a double treatment, 10 minutes apart, on the first day. Standard of care will include evaluation to document, off-loading adequate arterial flow, wound cleaning, removal of necrotic, infected and/or nonviable tissue by debridement, maintenance of moist wound environment, and management of infection.
Intervention: Placebo+SOC
Outcomes
Primary Outcomes
Proportion of subjects with complete wound closure during the 12 weeks of the Treatment Phase
Time Frame: 12 weeks
Complete wound closure is defined as 100% re-epithelialization without drainage or dressing requirements confirmed at two consecutive study visits 2 weeks apart. Complete wound closure will be evaluated by the blinded evaluator.
Secondary Outcomes
- Wound Area Change (%) during the 12 weeks of the Treatment Phase(12 weeks)
- Change in hemoglobin from baseline to subsequent scheduled visits(Up to 24 weeks)
- Change in Absolute Neutrophil Counts (ANC) from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in alkaline phosphatase levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in total bilirubin levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in cholesterol (total) levels from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in potassium levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Change in pH of urine specimens from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in ketone levels in urine from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in respiratory rate from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in physical examinations for neurologic parameters from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in blood glucose (random) levels from baseline to subsequent scheduled visits(Up to 24 weeks)
- Change in platelets from baseline to subsequent scheduled visits(Up to 24 weeks)
- Change in occult blood in urine samples from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in physical examination for cardiovascular parameters from baseline to subsequent scheduled visits(Up to 24 weeks)
- Change in White Blood Cells (WBC) from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in aspartate aminotransferase (AST) levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in total protein levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in albumin levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in serum creatinine levels levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in sodium levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in glucose levels in urine from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in leucocyte esterase levels in urine from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in nitrite levels in urine from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in physical examinations for musculoskeletal and extremities from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in physical examinations for dermatologic parameters from baseline to subsequent scheduled visits(Up to 24 weeks)
- Incidence and severity of treatment-emergent adverse events (TEAEs), including serious adverse events and adverse events resulting in permanent discontinuation of protocol-defined therapy(Up to 24 weeks)
- Change in Red Blood Cells (RBC) from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in alanine aminotransferase (ALT) levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in urea levels levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in bicarbonate levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Change in color of urine from baseline to subsequent scheduled visits(Up to 24 weeks)
- Time to complete wound closure during the 12 weeks of the Treatment Phase(12 weeks)
- Frequency of required debridement during the 12 weeks of the Treatment Phase(12 weeks)
- Change in Hematocrit (HCT) from baseline to subsequent scheduled visits.(Up to 24 weeks)
- Changes in Lactate dehydrogenase (LDH) levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in chloride levels in blood from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in calcium levels in blood from baseline to subsequent scheduled visits.(Up to 24 weeks)
- Change in appearance of urine from baseline to subsequent scheduled visits(Up to 24 weeks)
- Change in specific gravity of urine from baseline to subsequent scheduled visits(Up to 24 weeks)
- Change in microscopic examination of urine specimens from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in bilirubin levels in urine from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in physical examination for general appearance, head, ears, eyes, nose, throat (HEENT) from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in urobilinogen levels in urine from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in physical examinations for respiratory parameters from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in physical examinations for lymphatic parameters from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in blood pressure from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in heart rate from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in oral temperature from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in physical examinations for genitourinary parameters from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in Wound-Q Health-Related Quality of Life outcome during the 12 weeks of the Treatment Phase as measured by changes in the subject response to the Wound-Q Health-Related Quality of Life scale(12 weeks)
- Changes in physical examinations for gastrointestinal parameters from baseline to subsequent scheduled visits(Up to 24 weeks)
- Changes in physical examinations for psychiatric parameters from baseline to subsequent scheduled visits(Up to 24 weeks)