A Trial to Assess Safety and Efficacy of Topical MBN-101 in Patients With Moderate/ Severe DFI

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multi-center study, in patients with moderate to severe diabetic foot infection (DFI), that will be conducted in two parts. In Part I, patients will be enrolled into 1 of 3 escalating dose cohorts at a ratio of 3:1 (Active to Placebo). In Part II, patients will be randomized in a 1:1 ratio (Active to Placebo) based on the optimal dose demonstrated in Part I. Patients will be randomized to receive either topical application of MBN-101 or topical application of vehicle, applied directly to the target site, 3 times per week, for a minimum of 14 days and up to a maximum of 21 days. All patients will also receive systemic antibiotic treatment.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, multi-center study that will be conducted in two parts. In Part I, patients will be enrolled into escalating dose cohorts (150, 375, or 600 µg/mL) (N=16/cohort) at a ratio of 3:1 (Active to Placebo). In Part II, patients will be randomized in a 1:1 ratio (Active to Placebo) based on the optimal dose demonstrated in Part I. Patients with diabetes mellitus and a foot infection with an Infectious Disease Society of America (IDSA) infection severity rating of moderate or severe will be eligible for the trial. Both inpatients and outpatients are eligible if they meet all inclusion/exclusion criteria, however all enrolled patients must remain in-hospital for the first 24 hours after initial dosing. Patients with a need for surgical therapy (e.g., incision and drainage or removal of necrotic tissue) beyond standard bedside wound debridement should not be enrolled. Patients will be randomized to receive either topical application of MBN-101 or topical application of vehicle, applied directly to the target site, 3 times per week, for a minimum of 14 days and up to a maximum of 21 days. The determination to stop topical antibiotic therapy will be at the discretion of the principal investigator, and should be based on the resolution of findings of infection. All patients will also receive systemic antibiotic treatment based on the protocol defined algorithm. Systemic antibiotic therapy should continue until, but not beyond, the resolution of findings of infection, as outlined in the 2012 IDSA clinical practice guideline for the diagnosis and treatment of diabetic foot infections,

Official Title
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A Phase 1b/2a Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Efficacy of Adjunctive Treatment With Topically Applied MBN-101 in Patients With Moderate to Severe Diabetic Foot Infection (DFI)

Conditions
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Diabetic Foot Infection

Intervention / Treatment
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* Drug: MBN-101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has diabetes mellitus, according to the American Diabetes Association (ADA) criteria Has a foot infection as defined by the IDSA guidelines, with a severity rating of moderate or severe Either no current or recent (within 72 hours) antibiotic therapy for the DFI, Has documented adequate arterial perfusion in the affected limb (either palpable dorsalis pedis or posterior tibial pulses, or normal Doppler wave forms, or a toe blood pressure ≥ 45 mm Hg, or an ankle-brachial index (ABI) of >0.6) Exclusion Criteria: Proven or highly suspected, involvement of bone (i.e., osteomyelitis) More than one concurrent, infected, diabetic foot ulcer Hemoglobin A1c > 11 on the day of presentation Requirement for ongoing immunosuppressive therapy (topical or inhaled corticosteroids are permitted) Serum creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or Alkaline Phosphatase >2 times the upper limit of the normal range of the local testing laboratory Absolute neutrophil count <1000 Any condition that has required treatment with any other bismuth containing compound within the last 2 weeks (i.e., Kaopectate or Pepto-Bismol) Participation in an investigational trial to evaluate pharmaceuticals or biologics within the past 3 months Need for any surgical therapy beyond debridement to treat the diabetic foot ulcer (e.g., incision and drainage, removal of necrotic tissue) Planned lower extremity amputation that will include their infected ulcer Known allergy to bismuth and/or MBN-101 excipients (methylcellulose, Tween 80 (polysorbate 80)) Female patients who are pregnant, lactating, or who have a positive serum human chorionic gonadotropin (pregnancy) as determined by laboratory testing Immunocompromised due to illness or organ transplant History of any type of cancer (excluding non-melanoma localized skin cancer or completely excised and cured carcinoma-in-situ of uterine cervix) History of major medical noncompliance Other medical conditions which, in the opinion of the Principal Investigator, would jeopardize the safety of the study subject or impact the validity of the study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MBN-101<br>MBN-101: a suspension of 150, 375, or 600 microgram (µg)/milliliter (mL) (w:v) BisEDT drug particles in suspension in 3% methylcellulose / 0.5% polysorbate 80 / 10 millimole (mM) sodium chloride / 10 mM sodium phosphate. | Drug: MBN-101<br>* Topical application<br>* Other names: BisEDT;|
| Placebo Comparator: Vehicle<br>MBN-101 diluent (placebo): 3% methylcellulose / 0.5% polysorbate 80 / 10 mM sodium chloride / 10 mM sodium phosphate | Drug: Placebo<br>* Topical application<br>* Other names: Vehicle;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with treatment-related adverse events | Safety and tolerability will be assessed by treatment-related adverse events | From the start of dosing upto 4 weeks following the completion of dosing | 
| Proportion of participants who are clinically cured | Clinical cure is defined as the resolution of clinical signs and symptoms of infection 2 weeks following the end of treatment (EOT) | 2 weeks following completion of dosing (up to 5 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who are microbiologically cured | Microbiological cure is defined as the eradication of baseline pathogens 2 weeks following the end of treatment (EOT). | 2 weeks following completion of dosing (up to 5 weeks) |