Diabetic Foot UlcerPhase 1NTCDUNCT06020664
NOX1416 in Treatment of Chronic Non-Healing Diabetic Foot Ulcers (NTCDU)
A Phase 1 study testing NOX-1416+SOC in people with Diabetic Foot Ulcer, run by NOxy Health Products, LLC at 6 sites in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diabetic Foot Ulcer
- What is being tested?
- NOX-1416+SOC
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 6 sitesIsrael
- Study dates
- 16 Aug 2023to 24 Nov 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Ulcer must be non-healing as defined as <35% 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.
- 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.
- Clinically normal resting ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.
- 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.
- Subject is able and willing to comply with study procedures and applicable dressing changes.
- 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 / physical ability.
- A signed and dated informed consent form has been obtained from the subject.
Who cannot join
- 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
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- 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
- Albumin < 2.5 g/dL
- Renal function studies [Serum Creatinine and Urea] > 3x the upper limit of normal
- 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:
- Vasculitis or connective tissue disease
- Buerger's disease, Raynaud's or other peripheral vascular disease.
- Clinically significant claudication or peripheral edema on the affected limb
- Acute or unstable Charcot foot
- Aplastic anemia or sickle cell anemia
- Current sepsis
- 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
- Severe Liver disease
- End-stage renal disease
- Severe malnutrition
- Immunosuppression
- Acquired immune deficiency syndrome (AIDS) or HIV positive
- Past or present malignancy below the knee on the same limb as the Target Ulcer;
- History of radiation at the Target Ulcer site.
- 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.
- immunosuppressants (including chronic systemic corticosteroids)
- cytotoxic chemotherapy
- cytostatic therapy
- Lower limb revascularization surgery (e.g., angioplasty, artery bypass surgery,)
- application of bioengineered tissue or skin substitutes
- use of any investigational drug(s)
- Subjects who have previously received NOX1416 treatment
- Has a known hypersensitivity to any of the investigational drug components
- Subject is susceptible to hemorrhaging or has a congenital or acquired predisposition to hemorrhaging.
- Any reason that the subjects may need to be admitted to inpatient acute care in the opinion of the Investigator.
- Has any other factor which may, in the opinion of the investigator, compromise participation and/or follow-up in the study.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Israel6 sites
Soroka Medical Center (Site 106)
Beersheba
Carmel Medical Center (Site 104)
Haifa
Shaare Zedek Hospital (site 101)
Jerusalem, 9103102
Hadassah Medical Organization (Site 105)
Jerusalem
Meir Medical Center (Site 103)
Jerusalem
Laniado Hospital (Site 102)
Netanya
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Diabetic Foot Ulcer
- Being tested
- NOX-1416+SOC, Placebo+SOC
- Medical subject headings
- Diabetic Foot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NOX-1416+SOCDrug
Also called Advanox
NOX1416+SOC as provided in Arm/group description
Placebo+SOCOther
Placebo+SOC as provided in Arm/group description
| Study group | Role | What they receive |
|---|---|---|
| NOX1416+SOC | Experimental | 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. Receives: Drug: NOX-1416+SOC |
| Placebo+SOC | Placebo comparator | 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. Receives: Other: Placebo+SOC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects with complete wound closure during the 12 weeks of the Treatment Phase
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.
Measured: 12 weeks
Secondary outcomes (53)
Wound Area Change (%) during the 12 weeks of the Treatment Phase
Wound area change is defined as the percentage of wound area change as measured by Swift Imaging device.
Measured: 12 weeks
Time to complete wound closure during the 12 weeks of the Treatment Phase
Complete wound closure was 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.
Measured: 12 weeks
Frequency of required debridement during the 12 weeks of the Treatment Phase
Debridement refers to the process of removing dead/ infected tissue to promote wound healing.
Measured: 12 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
A treatment-emergent adverse event (TEAE) refers to any adverse event that occurs after the first administration of investigational product, i.e., NOX-1416 or the placebo, in this study.
Measured: Up to 24 weeks
Change in hemoglobin from baseline to subsequent scheduled visits
Analysis will be done for Hemoglobin counts.
Measured: Up to 24 weeks
Change in Hematocrit (HCT) from baseline to subsequent scheduled visits.
Analysis will be done for Hematocrit (HCT).
Measured: Up to 24 weeks
Change in Red Blood Cells (RBC) from baseline to subsequent scheduled visits
Analysis will be done for Red Blood Cells (RBC).
Measured: Up to 24 weeks
Change in White Blood Cells (WBC) from baseline to subsequent scheduled visits
Analysis will be done for White Blood Cells (WBC) with total and differential count.
Measured: Up to 24 weeks
Change in Absolute Neutrophil Counts (ANC) from baseline to subsequent scheduled visits
Analysis will be done for levels of Absolute Neutrophil Count (ANC).
Measured: Up to 24 weeks
Changes in alkaline phosphatase levels in blood from baseline to subsequent scheduled visits
Analysis will be done for alkaline phosphatase levels as an indicator of Hepatic function.
Measured: Up to 24 weeks
Changes in alanine aminotransferase (ALT) levels in blood from baseline to subsequent scheduled visits
Analysis will be done for alanine aminotransferase (ALT) as an indicator of Hepatic function.
Measured: Up to 24 weeks
Changes in total bilirubin levels in blood from baseline to subsequent scheduled visits
Analysis will be done for total bilirubin as an indicator of Hepatic function.
Measured: Up to 24 weeks
Changes in aspartate aminotransferase (AST) levels in blood from baseline to subsequent scheduled visits
Analysis will be done for aspartate aminotransferase (AST) as an indicator of Hepatic function.
Measured: Up to 24 weeks
Changes in total protein levels in blood from baseline to subsequent scheduled visits
Analysis will be done for total protein as an indicator of Hepatic function.
Measured: Up to 24 weeks
Changes in albumin levels in blood from baseline to subsequent scheduled visits
Analysis will be done for albumin as an indicator of Hepatic function.
Measured: Up to 24 weeks
Changes in blood glucose (random) levels from baseline to subsequent scheduled visits
Analysis will be done for glucose (random) levels.
Measured: Up to 24 weeks
Changes in cholesterol (total) levels from baseline to subsequent scheduled visits
Analysis will be done for cholesterol (total) levels.
Measured: Up to 24 weeks
Changes in Lactate dehydrogenase (LDH) levels in blood from baseline to subsequent scheduled visits
Analysis will be done for Lactate dehydrogenase (LDH) as an indicator of Hepatic function.
Measured: Up to 24 weeks
Change in platelets from baseline to subsequent scheduled visits
Analysis will be done for platelets levels.
Measured: Up to 24 weeks
Changes in serum creatinine levels levels in blood from baseline to subsequent scheduled visits
Analysis will be done for serum creatinine as an indicator of Renal function.
Measured: Up to 24 weeks
Changes in urea levels levels in blood from baseline to subsequent scheduled visits
Analysis will be done for urea as an indicator of Renal function.
Measured: Up to 24 weeks
Changes in sodium levels in blood from baseline to subsequent scheduled visits
Analysis will be done for electrolytes like sodium.
Measured: Up to 24 weeks
Changes in potassium levels in blood from baseline to subsequent scheduled visits
Analysis will be done for electrolytes like potassium.
Measured: Up to 24 weeks
Changes in chloride levels in blood from baseline to subsequent scheduled visits
Analysis will be done for electrolytes like chloride.
Measured: Up to 24 weeks
Changes in calcium levels in blood from baseline to subsequent scheduled visits.
Analysis will be done for electrolytes like calcium.
Measured: Up to 24 weeks
Changes in bicarbonate levels in blood from baseline to subsequent scheduled visits
Analysis will be done for electrolytes like bicarbonate.
Measured: Up to 24 weeks
Change in color of urine from baseline to subsequent scheduled visits
Urine samples will be tested for their color.
Measured: Up to 24 weeks
Change in appearance of urine from baseline to subsequent scheduled visits
Urine samples will be tested for their appearance.
Measured: Up to 24 weeks
Change in specific gravity of urine from baseline to subsequent scheduled visits
Urine samples will be tested for its specific gravity.
Measured: Up to 24 weeks
Change in pH of urine specimens from baseline to subsequent scheduled visits
Urine samples will be tested for pH levels.
Measured: Up to 24 weeks
Change in microscopic examination of urine specimens from baseline to subsequent scheduled visits
Urine samples will be tested for microscopic examination of urine sediment.
Measured: Up to 24 weeks
Changes in glucose levels in urine from baseline to subsequent scheduled visits
Urine samples will be tested for presence or absence of occult blood.
Measured: Up to 24 weeks
Change in occult blood in urine samples from baseline to subsequent scheduled visits
Urine samples will be tested occult blood.
Measured: Up to 24 weeks
Changes in ketone levels in urine from baseline to subsequent scheduled visits
Urine samples will be tested for ketones.
Measured: Up to 24 weeks
Changes in leucocyte esterase levels in urine from baseline to subsequent scheduled visits
Urine samples will be tested for leucocyte esterase levels.
Measured: Up to 24 weeks
Changes in nitrite levels in urine from baseline to subsequent scheduled visits
Urine samples will be tested for nitrite levels.
Measured: Up to 24 weeks
Changes in bilirubin levels in urine from baseline to subsequent scheduled visits
Urine samples will be tested for bilirubin.
Measured: Up to 24 weeks
Changes in urobilinogen levels in urine from baseline to subsequent scheduled visits
Urine samples will be tested for urobilinogen levels.
Measured: Up to 24 weeks
Changes in physical examination for general appearance, head, ears, eyes, nose, throat (HEENT) from baseline to subsequent scheduled visits
The physical examination will include routine examinations for the following: constitutional/general appearance, head, ears, eyes, nose, throat (HEENT).
Measured: Up to 24 weeks
Changes in physical examination for cardiovascular parameters from baseline to subsequent scheduled visits
The investigator will classify cardiovascular parameters as normal or abnormal. If abnormal, the investigator will specify if the abnormalities are clinically significant or not clinically significant.
Measured: Up to 24 weeks
Changes in physical examinations for musculoskeletal and extremities from baseline to subsequent scheduled visits
The investigator will classify musculoskeletal and extremities parameters as normal or abnormal. If abnormal, the investigator will specify if the abnormalities are clinically significant or not clinically significant.
Measured: Up to 24 weeks
Changes in physical examinations for dermatologic parameters from baseline to subsequent scheduled visits
The investigator will classify dermatologic parameters as normal or abnormal. If abnormal, the investigator will specify if the abnormalities are clinically significant or not clinically significant.
Measured: Up to 24 weeks
Changes in physical examinations for neurologic parameters from baseline to subsequent scheduled visits
The investigator will classify neurologic parameters as normal or abnormal. If abnormal, the investigator will specify if the abnormalities are clinically significant or not clinically significant.
Measured: Up to 24 weeks
Changes in physical examinations for respiratory parameters from baseline to subsequent scheduled visits
The investigator will classify respiratory parameters as normal or abnormal. If abnormal, the investigator will specify if the abnormalities are clinically significant or not clinically significant.
Measured: Up to 24 weeks
Changes in physical examinations for gastrointestinal parameters from baseline to subsequent scheduled visits
The investigator will classify gastrointestinal parameters as normal or abnormal. If abnormal, the investigator will specify if the abnormalities are clinically significant or not clinically significant.
Measured: Up to 24 weeks
Changes in physical examinations for genitourinary parameters from baseline to subsequent scheduled visits
The investigator will classify genitourinary parameters as normal or abnormal. If abnormal, the investigator will specify if the abnormalities are clinically significant or not clinically significant.
Measured: Up to 24 weeks
Changes in physical examinations for lymphatic parameters from baseline to subsequent scheduled visits
The investigator will classify lymphatic parameters as normal or abnormal. If abnormal, the investigator will specify if the abnormalities are clinically significant or not clinically significant.
Measured: Up to 24 weeks
Changes in physical examinations for psychiatric parameters from baseline to subsequent scheduled visits
The investigator will classify psychiatric parameters as normal or abnormal. If abnormal, the investigator will specify if the abnormalities are clinically significant or not clinically significant.
Measured: Up to 24 weeks
Changes in blood pressure from baseline to subsequent scheduled visits
Systolic and diastolic blood pressure will be measured in supine position after subject has been resting for 5 minutes.
Measured: Up to 24 weeks
Changes in heart rate from baseline to subsequent scheduled visits
Heart rate will be measured after subject has been resting for 5 minutes.
Measured: Up to 24 weeks
Changes in respiratory rate from baseline to subsequent scheduled visits
Respiratory rate will be measured in breaths per minute.
Measured: Up to 24 weeks
Changes in oral temperature from baseline to subsequent scheduled visits
Oral temperature will be measured in Fahrenheit.
Measured: 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
The Wound-QoL (Questionnaire on quality of life with chronic wounds) Wound-Q Health-Related Quality of Life assessment includes Life Impact, Psychological and Social scales. The minimum/maximum scores lie between 23 - 92. A lower score indicates a worse outcome.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2023
- Study start16 Aug 2023
- Primary completionSep 2024 (estimated)
- Study completion24 Nov 2024 (estimated)
Why it stopped: The NO-002 study had to be paused because of enrollment disruptions due to the current situation in Israel, and concerns over the placebo batch stability results.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Foot UlcerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A total of 30 subjects will be randomized 1:1 to receive either NOX1416 + SOC or Placebo + SOC (15 per group).
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NOxy Health Products, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gabriel Halperin, MD, Study chair, Mission Community Hospital, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06020664
- Sponsor's protocol ID
- NO-002
- Acronym
- NTCDU
- Status last verified
- Jan 2024
- First submitted
- 10 Jul 2023
- Last updated
- 16 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06020664
- Acronym / sponsor ID
- NTCDU / NO-002
- Conditions
- Diabetic Foot Ulcer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: The NO-002 study had to be paused because of enrollment disruptions due to the current situation in Israel, and concerns over the placebo batch stability results.
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- NOxy Health Products, LLCIndustry (pharma, biotech, devices)
- Study start
- 16 Aug 2023 (actual)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- 24 Nov 2024 (estimated)
- First posted
- 31 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- A total of 30 subjects will be randomized 1:1 to receive either NOX1416 + SOC or Placebo + SOC (15 per group).
| Arm | Type | Receives |
|---|---|---|
| NOX1416+SOC | Experimental | Drug: NOX-1416+SOCNOX1416 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. |
| Placebo+SOC | Placebo comparator | Other: Placebo+SOCPlacebo 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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:
- 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.
Key exclusion criteria (39 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NOX-1416+SOCAlso: AdvanoxNOX1416+SOC as provided in Arm/group description | Drug | NOX1416+SOC |
| Placebo+SOCPlacebo+SOC as provided in Arm/group description | Other | Placebo+SOC |
Primary outcome
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.
53 secondary outcomes
Wound Area Change (%) during the 12 weeks of the Treatment Phase
Time frame: 12 weeks
Time to complete wound closure during the 12 weeks of the Treatment Phase
Time frame: 12 weeks
Frequency of required debridement during the 12 weeks of the Treatment Phase
Time frame: 12 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
Time frame: Up to 24 weeks
Change in hemoglobin from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Change in Hematocrit (HCT) from baseline to subsequent scheduled visits.
Time frame: Up to 24 weeks
Change in Red Blood Cells (RBC) from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Change in White Blood Cells (WBC) from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Change in Absolute Neutrophil Counts (ANC) from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in alkaline phosphatase levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in alanine aminotransferase (ALT) levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in total bilirubin levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in aspartate aminotransferase (AST) levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in total protein levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in albumin levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in blood glucose (random) levels from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in cholesterol (total) levels from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in Lactate dehydrogenase (LDH) levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Change in platelets from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in serum creatinine levels levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in urea levels levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in sodium levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in potassium levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in chloride levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in calcium levels in blood from baseline to subsequent scheduled visits.
Time frame: Up to 24 weeks
Changes in bicarbonate levels in blood from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Change in color of urine from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Change in appearance of urine from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Change in specific gravity of urine from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Change in pH of urine specimens from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Change in microscopic examination of urine specimens from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in glucose levels in urine from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Change in occult blood in urine samples from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in ketone levels in urine from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in leucocyte esterase levels in urine from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in nitrite levels in urine from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in bilirubin levels in urine from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in urobilinogen levels in urine from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in physical examination for general appearance, head, ears, eyes, nose, throat (HEENT) from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Changes in physical examination for cardiovascular parameters from baseline to subsequent scheduled visits
Time frame: Up to 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gabriel Halperin, MD study chair
Mission Community Hospital, CA
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NOX-1416+SOC in people with Diabetic Foot Ulcer, run by NOxy Health Products, LLC at 6 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 16 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of subjects with complete wound closure during the 12 weeks of the Treatment Phase (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2024.