Overview

The goal of this multi-center, randomized, placebo-controlled, evaluator-blinded study is to assess the safety and efficacy 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 Standard of Care (SOC).

The primary objective of the study is to demonstrate the safety and tolerability of NOX1416 as adjunct to SOC. The secondary objective is to evaluate the clinical benefit of daily NOX1416, as an adjunct to standard of care SOC. Each site will assign a physician (or designee) to serve as the blinded evaluator who is responsible for assessing the study endpoints. The blinded evaluator will not be involved in the clinical care of subjects.

Eligibility

Inclusion Criteria:

        Subjects will be eligible for enrollment in the study only if they meet ALL the following
        criteria at time of Screening:
          1. Male or female subjects aged 18 to 80 years (inclusive) with Type 1 or Type 2 diabetes
             undergoing therapy for glycemic control.
          2. Subject has a glycosylated hemoglobin, HbA1c ≤ 12%. Note: Prior documented HbA1c
             within the last 3 months of the Screening Visit is acceptable.
          3. Presence of at least one diabetic foot ulcer that meets all of the following criteria:
               1. A full-thickness ulcer of University of Texas Wound Classification (UTWCS) Grade
                  I or II
               2. Ulcer is located on or below the malleoli
               3. Ulcer size (area) is ≥ 1 cm2 and ≤ 10 cm2 (post-debridement at time of
                  randomization)
               4. Unresponsive to standard ulcer care for ≥3 months (at time of screening)
               5. There is a minimum 1 cm margin between the qualifying Target Ulcer and any other
                  ulcers on the specified foot, post-debridement)
               6. No exposed bone and no tunneling, undermining, or sinus tracts
               7. Ulcer must be non-healing as defined as < 25% reduction in size in response to
                  standard of care during the two-week run-in Screening Period (between the first
                  Screening Visit and Baseline). Note: Criterion 3(g) will be evaluated at the time
                  of randomization. If the subject has more than one qualifying diabetic foot
                  ulcer, the ulcer designated as the Target Ulcer will be at the discretion of the
                  Investigator.
          4. Subject has adequate vascular perfusion of the affected limb, confirmed by
             Ankle-Brachial Index (ABI) ≥ 0.6 and ≤ 1.2. ABI results within the last 3 months of
             Screening are acceptable. The assessment may also be performed between SV1 and SV2.
             Note: If the ABI measurement is >1.20, confirmatory tests (Great toe pressure and/or
             TcPO2 at the foot) will be performed. A subject will be considered eligible for
             inclusion in this study if Great toe pressure ≥ 40mmHg or TcPO2 ≥ 40 mmHg at the foot.
             Prior documented flow study within the last 3 months of the Screening Visit is
             acceptable.
          5. Subject does not smoke or use tobacco products.
          6. Subject, if female of child-bearing potential, has a negative serum pregnancy test at
             screening, must not be breastfeeding, and willing to use acceptable methods of
             contraception (birth control pills, barriers, or abstinence) throughout the study.
          7. Subject is able and willing to comply with study procedures and applicable dressing
             changes.
          8. Subject demonstrates cognitive and physical ability to administer the treatment as
             determined by the clinician. If a caregiver will administer the treatment, the
             caregiver must demonstrate cognitive and physical ability.
          9. A signed and dated informed consent form has been obtained from the subject.
        Exclusion Criteria:
        Subjects meeting ANY of the following criteria at time of Screening will be excluded from
        enrollment:
          1. 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.
          2. 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.
          3. 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
          4. Subjects with a gangrenous or ischemic toe that may need to be amputated in the
             opinion of the Investigator.
          5. Current smoker or tobacco product user
          6. Body mass index (BMI) > 40kg/m2
          7. Methemoglobin > 5% at SV1
          8. Laboratory values at Screening of:
               1. Hemoglobin < 8.5 g/dL
               2. White Blood Cells (WBC) < 3.0 X 109 cells/L and > 11 x 109 cells/L
               3. Liver function studies [Total bilirubin, aspartate aminotransferase (AST) and
                  alanine transaminase (ALT)] > 3x the upper limit of normal
               4. Albumin < 2.5 g/dL
               5. Renal function studies [Estimated Glomerular Filtration Rate] < 45
          9. Presence of any clinically significant medical condition(s) that, in the opinion of
             the Investigator, could interfere with wound healing, including but not limited to the
             following:
               1. Vasculitis or connective tissue disease
               2. Buerger's disease, Raynaud's or other peripheral vascular disease.
               3. Clinically significant claudication or peripheral edema on the affected limb
               4. Acute or unstable Charcot foot
               5. Aplastic anemia or sickle cell anemia
               6. Current sepsis
               7. Severe heart diseases such as congestive heart failure (NYHA Class III or IV),
                  coronary heart disease with ST segment elevation, myocardial infarction, or
                  coronary artery bypass graft or percutaneous transluminal coronary angioplasty
                  within the last 6 months
               8. Severe liver disease
               9. End-stage renal disease
              10. Severe malnutrition
              11. Immunosuppression
              12. Acquired immune deficiency syndrome (AIDS) or HIV positive
              13. Past or present malignancy below the knee on the same limb as the Target Ulcer;
              14. History of radiation at the Target Ulcer site.
         10. Subject is currently receiving (i.e., within 30 days of T1 visit) or scheduled to
             receive any of following medication or therapies during the course of the study.
               1. Immunosuppressants (including chronic systemic corticosteroids)
               2. Cytotoxic chemotherapy
               3. Cytostatic therapy
               4. Lower limb revascularization surgery (e.g., angioplasty, artery bypass surgery,)
               5. application of bioengineered tissue or skin substitutes
               6. use of any investigational drug(s)
         11. Subjects who have previously received NOX1416 treatment
         12. Has a known hypersensitivity to any of the investigational drug components
         13. Subject is susceptible to hemorrhaging or has a congenital or acquired predisposition
             to hemorrhaging.
         14. Any reason that the subjects may need to be admitted to inpatient acute care in the
             opinion of the Investigator.
         15. Has any other factor which may, in the opinion of the investigator, compromise
             participation and/or follow-up in the study.