Open Label, Single-dose, Dose Escalating Evaluation of the Safety and Tolerability of DBI-001 in Patients With T. Pedis

Study Overview
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Brief Summary
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This is an open- label, single- dose, dose escalating evaluation of the safety and tolerability of three dose levels of DBI-001 in patients with Tinea pedis. The purpose of the current protocol is to establish the safety and tolerability of a single application of J. lividum to the feet of patients with proven T. pedis. In addition, the effect of J liv on the T. pedis will also be evaluated.

Detailed Description
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Open- label, single- dose, dose escalating evaluation of the safety and tolerability of three dose levels of DBI-001 in patients with Tinea pedis. Study Objectives and Purpose The purpose of the study is to evaluate the safety and tolerability of DBI-001 in patients with Tinea pedis. Secondly to evaluate presence or persistence of J. lividum of DBI-001 following a single application of DBI-001. Thirdly to see the effect on the abundance of T. rubrum. Lastly to see the effect of a single application of DBI-001 on the signs and symptoms of interdigital T. pedis. Tolerability will be evaluated through assessment of selected local signs and symptoms (pain / burning / stinging, pruritus, erythema, edema, and scabbing / crusting). Any local skin reaction that requires use of a concomitant therapy or study discontinuation will be reported

Official Title
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Clinical Study Protocol Number DBI-201. Open Label, Single-dose, Dose Escalating Evaluation of the Safety and Tolerability of DBI-001 in Patients With Tinea Pedis

Conditions
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Tinea Pedis

Intervention / Treatment
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* Drug: J. Lividum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following criteria to be included in the study: Witnessed, signed informed consent approved by Institutional Review Board/Independent Ethics Committee. A signed Health Information Portability and Accountability Act (HIPAA) authorization form which permits the use and disclosure of subject's individually identifiable health information. Male Subjects of any race 18 years of age and older. Subjects with a clinical diagnosis of interdigital T. pedis T. pedis interdigital defined as lesions localized to the interdigital spaces or predominantly interdigital, but may extend to other areas of the foot (the non-interdigital lesions should not be hyperkeratotic, i.e., characteristic of tinea pedis moccasin). Provisionally confirmed diagnosis at baseline by a positive potassium hydroxide (KOH) wet mount at the clinical site. The sum of the clinical signs and symptoms scores of the target lesion is at least 4 using the Grading and signs and symptoms of T. pedis detailed in section 6.6.1, including a minimum score of at least 2 for erythema AND a minimum score of 2 for either scaling/fissures or pruritus/burning (on a scale of 0-3, where 2 indicates moderate severity). - Exclusion Criteria: Subjects with the following will be excluded from this study: Any dermatological conditions that could interfere with clinical evaluations. Any underlying disease(s) or some other dermatological condition that requires the use of interfering topical or systemic therapy. Subjects that have not undergone the specified washout period(s) for the following topical preparations or subjects who require the concurrent use of any of the following topical medications applied to the foot: Topical astringents and abrasives (e.g. Burrow's solution) 1 week Topical antibiotics and antifungal on the infected area (e.g. Neomycin, Miconazole, Clotrimazole, Terbinafine) 2 weeks Anti-inflammatories, corticosteroids, topical immunomodulators (e.g. Pimecrolimus, Tacrolimus) 4 weeks Subjects that have not undergone the specified washout period(s) for the following systemic medications or subjects who require the concurrent use of any of the following systemic medications: Corticosteroids (including intramuscular injections) (e.g. Triamcinolone acetonide) 4 weeks Antibiotics (e.g. Tetracycline, Cephalosporins, etc.) and/or Antifungal agents (e.g. Fluconazole, Itraconazole, Terbinafine, etc.) 4 weeks Systemic immunomodulators (e.g. Cyclophosphamide, Azathioprine, Biologicals-Monoclonal Antibodies. 4 weeks Subjects with the following will be excluded from this study: Any dermatological conditions that could interfere with clinical evaluations. Any underlying disease(s) or some other dermatological condition that requires the use of interfering topical or systemic therapy. Subjects that have not undergone the specified washout period(s) for the following topical preparations or subjects who require the concurrent use of any of the following topical medications applied to the foot: Topical astringents and abrasives (e.g. Burrow's solution) 1 week Topical antibiotics and antifungal on the infected area (e.g. Neomycin, Miconazole, Clotrimazole, Terbinafine) 2 weeks Anti-inflammatories, corticosteroids, topical immunomodulators (e.g. Pimecrolimus, Tacrolimus) 4 weeks Subjects that have not undergone the specified washout period(s) for the following systemic medications or subjects who require the concurrent use of any of the following systemic medications: Corticosteroids (including intramuscular injections) (e.g. Triamcinolone acetonide) 4 weeks Antibiotics (e.g. Tetracycline, Cephalosporins, etc.) and/or Antifungal agents (e.g. Fluconazole, Itraconazole, Terbinafine, etc.) 4 weeks Systemic immunomodulators (e.g. Cyclophosphamide, Azathioprine, Biologicals-Monoclonal Antibodies. 4 weeks Treatment of any type of cancer within the last 6 months. History of any significant internal disease (which contraindicates use of live microbiome e.g. leukemia, liver failure, cardiovascular disease) Subjects who are known to be allergic to any of the test product(s) or any components in the test product(s) or history of hypersensitivity or allergic reactions to any of the study preparations as described in the Investigator's Brochure. AIDS or AIDS related complex by medical history. Known or suspected immune suppressive medications or diseases. Diabetes mellitus Type I or II by medical history. Peripheral vascular disease based on medical history. Any subject not able to meet the study attendance requirements. Subjects who have participated in any other trial of an investigational drug or device within 30 days prior to enrollment or participation in a research study concurrent with this study. -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: A single center open label dose escalating study design will be used in a population of patients with interdigital Tinea pedis. Each subject will have a single application of the test article applied to each foot. The three test articles will be a low dose, medium and a high dose of J. lividum. Each of the three groups will have 4 subjects. After the first cohort has completed their day 7 visits and if no significant tolerability of safety issues is identified the second cohort will be enrolled. After the second cohort has completed the day 7 visits and if no significant tolerability or safety issues are identified the third cohort will be enrolled. At all evaluations, signs and symptoms of application site reactions will be recorded at baseline, as well as days 2, 3, 7, 14, and 28.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort 1<br>Cohort 1 low dose of J. lividum | Drug: J. Lividum<br>* Investigational Product<br>* Other names: Janthinobacterium lividum;|
| Active Comparator: Cohort 2<br>Cohort 2 medium dose of J. lividum | Drug: J. Lividum<br>* Investigational Product<br>* Other names: Janthinobacterium lividum;|
| Active Comparator: Cohort 3<br>Cohort 3 - high dose of J. Lividum | Drug: J. Lividum<br>* Investigational Product<br>* Other names: Janthinobacterium lividum;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Tolerability | Tolerability will be evaluated through assessment local signs and symptoms. Scoring for Fissuring/Cracking, Erythema, Maceration, Scaling, Pruritus, Burning/Stinging: 0 = none (complete absence) = mild (slight) = moderate (definitely present) = severe (marked, intense) | Baseline (Day 1) to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy 1: Presence and Persistence of J. lividum | Proportion of samples at each time point in which J. lividum can be detected. | 28 Days | 
| Efficacy 2: Clinical Response | Changes in signs and symptoms of T. pedis Scoring Measure for Fissuring/Cracking, Erythema, Maceration, Scaling, Pruritus, Burning/Stinging: Scoring Measure: 0 = none (complete absence) = mild (slight) = moderate (definitely present) = severe (marked, intense) | 28 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dermatophytes, Dysbiosis, Microbiome