Clinical trial NCT04152226
Conditions: Tinea Pedis
Sponsor: DermBiont, Inc.
Start date: 2019-02-19; Completion date: 2019-04-30
Enrollment: 12 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
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. lividum on the T. pedis will also be evaluated.

Detailed description:
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 test product will be applied by study personnel at the investigational site. Each subject will have a single application of approximately 0.5 ml of the test article applied to each foot. Both affected and unaffected feet will be treated covering the web spaces, toes, toe nails as well as the plantar and lateral aspect of both feet. Each of the three groups will have 4 subjects. After the first cohort has completed their day 7 visits, if no significant tolerability or safety issues identified the second cohort will be enrolled. After the second cohort has completed the day 7 visits and if no significant tolerability of safety issues is identified the third cohort will be enrolled.

Arms: arm 1: Cohort 1 DBI-001 Gel with 10\^6 CFUs/ml of J.lividum arm 2: Cohort 2 DBI-001 Gel with 10\^7 CFUs/ml of J.lividum arm 3: Cohort 3 DBI-001 Gel with 10\^8 CFUs/ml of J.lividum
Interventions: intervention 1: Janthinobacterium lividum
Intervention descriptions: intervention 1: Investigational Product

Protocol documents:
Prot_SAP_000.pdf: 
 
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   
 
 
 
 
 
 
 
 
NCT Number: NCT04152226 
 
 
 
 
 
 
 
 
 
Document Date: 03/05/2019 
 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 1 of 41 
PROPRIETARY AND CONFIDENTIAL 
 
 
CLINICAL STUDY PROTOCOL 
 
 
Protocol Number DBI-201 
 
 
Open label, single-dose, dose escalating evaluation of the safety and tolerability of DBI-001 
in patients with Tinea pedis 
 
 
 
Development Phase of Study:   Phase 2 A 
Study Design:  
Open Label 
Date of Original Protocol: 
Date of Amendment 1: 
26 November 2018 
05 March 2019 
Sponsor Representative:  
International Dermatology Research, Inc. (IDR) 
Sponsor:  
DermBiont Inc. 
 
 
 
CONFIDENTIAL 
 
 
 
Part or all of the information in this protocol may be unpublished material. Accordingly, 
this protocol is to be treated as confidential and restricted to its intended use.  If a portion 
of this material is required for purposes of publication, authorization must be obtained 
from DermBiont, Inc. 
 
 
 
 
 
 
This protocol will be conducted in compliance with procedures outlined in this document, 
Good Clinical Practice (GCP) guidelines and applicable regulatory requirements.  This 
study will not be initiated without the approval of the Institutional Review Board (IRB) or 
Independent Ethics Committee (IEC).  Any changes to the protocol will be approved in 
writing by the IRB/IEC before implementation except where necessary to eliminate an 
immediate harm to the patient. 
 
 
 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 2 of 41 
PROPRIETARY AND CONFIDENTIAL 
 
PROTOCOL REVIEW AND APPROVALS 
Open label, single-dose, dose escalating evaluation of the safety and tolerability of DBI-001 
in patients with Tinea pedis 
 
 
 
Reviewed and approved by: 
 
 
Chief Executive Officer, 
Chief Medical Officer 
 
 
 
 
 
Signature 
Date 
                                   
 
  
Vice President, CMC  
and Technical Operations 
 
 
 
 
 
 
 
Signature 
Date 
 
 
 
 
Medical Director 
 
 
 
 
 
 
Signature 
Date 
 
 
 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 3 of 41 
PROPRIETARY AND CONFIDENTIAL 
 
Table of Contents 
Protocol Review and Approvals ............................................................................. 2 
Synopsis………. ............................................................................................... ……7 
1. 
Introduction .................................................................................................. 13 
1.1 
Background Information ............................................................................ 13 
1.2 
Rational… ..................................................................................................... 15 
2. 
Potential Risks and Benefits ........................................................................ 15 
2.1 
Potential Risks .............................................................................................. 15 
2.2 
Potential Benefits ......................................................................................... 16 
3. 
Study Objectives and Purpose .................................................................... 16 
4. 
Study Design and Endpoints ....................................................................... 16 
4.1 
Description of the Study Design ................................................................. 16 
4.2 
Study Endpoints ........................................................................................... 17 
4.2.1 Primary Endpoints ...................................................................................... 17 
4.2.2 Secondary Endpoints ................................................................................... 17 
4.2.3 Exploratory Endpoints ................................................................................ 17 
5. 
Investigational Product (IP) / Study Materials ......................................... 17 
5.1 
Investigational Product / Test Articles ....................................................... 17 
5.2 
Study Materials ............................................................................................ 18 
6. 
Study Procedures ......................................................................................... 18 
6.1 
Inclusion Criteria ......................................................................................... 18 
6.2 
Exclusion Criteria ........................................................................................ 19 
6.3 
Recruitment and Retention ......................................................................... 20 
6.4 
Withdrawal or Termination ....................................................................... 20 
6.4.1 Subject Withdrawal ..................................................................................... 20 
6.4.2 Study Discontinuation ................................................................................. 20 
6.4.3 Stopping Rules .............................................................................................. 21 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 4 of 41 
PROPRIETARY AND CONFIDENTIAL 
6.5 
Study Visits ................................................................................................... 24 
6.5.1 Screening Visit .............................................................................................. 24 
6.5.2 All Other Visits ............................................................................................. 24 
6.6 
Study Specific Procedures ........................................................................... 27 
6.6.1 Grading of signs and symptoms of T. pedis ............................................... 27 
6.6.2 T. pedis Investigator’s Static Global Assessment (ISGA) ........................ 29 
6.6.3 Local Tolerability for Areas Not Affected by T. Pedis ............................. 29 
6.6.4 Sample Collection ........................................................................................ 30 
6.7 
Study Drug Administration ........................................................................ 32 
6.8 
Concomitant medication and Excluded Therapy ..................................... 32 
6.9 
Investigational Product ............................................................................... 32 
6.10 Treatment Compliance ................................................................................ 33 
6.11 General Statistical Considerations ............................................................. 33 
6.12 Analysis of Data for Objectives .................................................................. 33 
6.13 Analysis Populations .................................................................................... 33 
6.14 Sample Size Determination ......................................................................... 34 
7. 
Assessment of Safety .................................................................................... 34 
7.1 
Safety Evaluations and Criteria ................................................................. 34 
7.2 
Adverse Event .............................................................................................. 34 
7.3 
Serious Adverse Event ................................................................................. 34 
7.4 
Unexpected Adverse Event ......................................................................... 35 
7.5 
Relationship of Adverse Events to Study Drug ......................................... 35 
8. 
Procedures for Adverse Event Recording and Reporting ....................... 36 
8.1 
Emergency Sponsor Contact ....................................................................... 36 
8.2 
Other Required Safety Assessments .......................................................... 36 
9. 
Special Requirements and Procedures ...................................................... 37 
9.1 
Study Monitoring ......................................................................................... 37 
9.2 
Audits and Inspections ................................................................................ 37 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 5 of 41 
PROPRIETARY AND CONFIDENTIAL 
9.3 
Data Quality Control and Quality Assurance ........................................... 37 
9.4 
Confidentiality .............................................................................................. 37 
9.5 
Subject Rights .............................................................................................. 38 
9.6 
Protocol Amendments ................................................................................. 38 
9.7 
Obligations of the Clinical Investigator ..................................................... 38 
9.8 
Institutional Review Board/Independent Ethics Committee ................... 39 
9.9 
Ethical Conduct of the Study ...................................................................... 39 
9.10 Written Informed Consent .......................................................................... 39 
9.11 Subject Data Protection ............................................................................... 40 
10. 
Data Handling and Retention of RECORDS ............................................ 40 
10.1 Paper and Electronic Case Report Form Completion ............................. 40 
10.2 Retention of Records ................................................................................... 40 
11. 
References ..................................................................................................... 40 
 
 
 






 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 8 of 41 
PROPRIETARY AND CONFIDENTIAL 
Methodology 
Open label, dose escalating 
Number of 
patients 
N=12 (3 cohorts) 
4 patients per treatment group  
Inclusion 
Criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subjects must meet all of the following criteria to be included in the 
study: 
1. Witnessed, signed informed consent approved by Institutional 
Review Board/Independent Ethics Committee.  
2. A signed Health Information Portability and Accountability Act 
(HIPAA) authorization form which permits the use and 
disclosure of subject’s individually identifiable health 
information.  
3. Male Subjects of any race 18 years of age and older.  
4. 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). 
 
5. Provisionally confirmed diagnosis at baseline by a positive 
potassium hydroxide (KOH) wet mount at the clinical site. 
 
6. 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). 
 
 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 9 of 41 
PROPRIETARY AND CONFIDENTIAL 
 
Exclusion 
Criteria  
Subjects with the following will be excluded from this study: 
1. Any dermatological conditions that could interfere with clinical 
evaluations. 
 
2. Any underlying disease(s) or some other dermatological 
condition that requires the use of interfering topical or systemic 
therapy. 
 
3. 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 
affected area (e.g. Neomycin, 
Miconazole, Clotrimazole, Terbinafine) 
2 weeks 
Anti-inflammatories, corticosteroids, 
topical immunomodulators (e.g. 
Pimecrolimus, Tacrolimus) 
4 weeks 
 
4. 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 
 
5. Treatment of any type of cancer within the last 6 months. 
6. History of any significant internal disease (which 
contraindicates use of live microbiome e.g. leukemia, liver 
failure, cardiovascular disease) 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 10 of 41 
PROPRIETARY AND CONFIDENTIAL 
7. 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. 
8. AIDS or AIDS related complex by medical history. 
9. Known or suspected immune suppressive medications or 
diseases. 
10. Diabetes mellitus Type I or II by medical history. 
11. Peripheral vascular disease based on medical history. 
12. Any subject not able to meet the study attendance requirements. 
13. 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. 
Test product, 
dose and mode 
of 
administration 
The test product will be applied by study personnel at the investigational 
site. Each subject will have a single application of approximately 0.5 ml 
of the test article applied to both affected and unaffected feet covering 
the web spaces, toes, toe nails as well as the plantar and lateral aspect of 
both feet. The product is formulated in a low viscosity aqueous gel and 
approximately 0.5 ml will be applied to each foot. The three dose groups 
are: 
Cohort 1 dose106 /ml CFUs of 
 
Cohort 2 dose 107/ml CFUs of 
 
Cohort 3 dose 108/ml CFUs of 
 
Duration of 
treatment 
A single application will be applied and then patients will be followed 
for 28 days 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 11 of 41 
PROPRIETARY AND CONFIDENTIAL 
Criteria for 
evaluation  
Evaluations will be made at Screening, Day 1 / Baseline prior to the 
application of the test article and then 1 hour after application and study 
days 2, 3+1 ,7+/-1, 14+/-2 and 28+/-2. 
Subjects will also be queried for adverse events starting after the 
informed consent is signed and all timepoints following application. 
Primary:   
• 
Signs and symptoms of irritation        
 
Secondary:  
• 
Data listing showing duration of time over which DBI-001 can 
be detected by molecular diagnosis    
• 
Change in abundance of T. rubrum by molecular diagnosis  
• 
Changes in the signs and symptoms of T. pedis 
• 
Changes in the T. pedis ISGA 
• 
Frequency of conventional culture negative  
• 
Frequency of KOH negative 
Statistical 
methods 
Descriptive 
 
Safety 
Results:  
 
Dermal Safety and Tolerability: Tolerability will be evaluated through 
assessment of selected local signs and symptoms (pain / burning, 
pruritus, erythema, edema, and scabbing/ crusting). Any local skin 
reaction that requires use of a concomitant therapy or causing study drug 
interruption or discontinuation should be reported as an AE. The scales 
to be used for assessing local skin reactions follow 
Adverse 
Events:  
 
During the study, subjects will be assessed for the occurrence of new and 
ongoing AEs. Descriptions of AEs will include the dates of onset and 
resolution (if resolved), maximum severity, and seriousness, corrective 
treatment, outcome, and the Investigator’s assessment of causality. AEs 
present at any visit will be followed to resolution (return to normal or to 
the baseline state) or until clinically stable as determined by the 
Investigator. 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 12 of 41 
PROPRIETARY AND CONFIDENTIAL 
Efficacy 
Results: 
 
• 
Proportion of samples at each time point in which 
 can 
be detected by molecular diagnosis. 
• 
Proportion of samples at each time point in which T. rubrum 
can be detected by molecular diagnosis 
• 
Relative abundance of T. rubrum at each time point 
• 
Change in abundance of T. rubrum   
• 
Changes in the signs and symptoms of T.  pedis 
• 
Changes in the T. pedis ISGA 
• 
Change from dermatophyte culture positive to culture negative 
• 
Change from KOH positive to KOH negative 
 
 
 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 13 of 41 
PROPRIETARY AND CONFIDENTIAL 
1. INTRODUCTION 
1.1 Background Information 
DBI-001 is a live bacterial product containing 
 
 This 
product is being developed as a topical probiotic for the treatment of fungal infections of the skin 
and nails. 
 is an aerobic Gram-negative bacterium commonly found in the soil, water, 
vegetables and grains from the human food chain, and on the skin of healthy humans. DBI-001 is 
a human derived commensal organism being employed as a topical probiotic. The strain of 
 
 in the DBI-001 product is a strain 
 that DermBiont isolated from the skin of a 
healthy young adult. Based on DNA sequencing this strain has no know virulence factors nor genes 
that would indicate antimicrobial resistance.  In vitro the 
 strain has been shown to inhibit 
the growth of T. rubrum. The 
 strain is sensitive to commonly used antibiotics. 
 
New strains of probiotics and their applicability for curing disease through topical application has 
been reviewed (Kerry et al 2018). The microbiome in health and disease was initially studied as it 
related to the microbiome of the gut. It is now well recognized that all human epithelial surfaces 
have a microbiome community that can contribute to health and diseases. There are distinct 
microbial communities in the gut, the skin, the respiratory tract, the oral cavity, and the genital 
urinary tract. 
 
The use of topical live bacterial products to treat skin diseases is a new and rapidly advancing 
therapeutic approach. To date at least three live bacterial products have been studied in the clinic. 
An ammonia oxidizing bacterium has been used in Phase 2 trials to treat acne patients ( 
https://clinicaltrials.gov/ct2/show/NCT02832063). A coagulase-negative Staphylococcus has 
been used to treat patients with atopic dermatitis (Williams and Gallo 2017). A strain of P. acnes 
has been used to treat acne patients.  
(https://www.clinicaltrials.gov/ct2/show/NCT03450369?term=Naked+Biome&rank=2). 
 
Application of 
 to the skin of amphibians has been shown to be able to treat and prevent 
the acquisition of a lethal cutaneous fungal infection(Brucker et al. 2008). 
 produces at 
least two anti-fungal compounds violacein and indole-3 carboxaldehyde. 
 
In vitro 
 has been shown to inhibit the growth of T. rubrum, a dermatophytic fungus 
commonly associated with diseases of the skin and nails in humans.   
 
There are a number of recognized skin diseases associated with a group of fungi called 
dermatophytes. These include various forms of Tinea pedis (athlete’s foot), onychomycosis (toe 
nail fungus), Tinea cruris (jock itch) and Tinea corporis (ring worm). Traditionally these are 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 14 of 41 
PROPRIETARY AND CONFIDENTIAL 
thought to be caused by an “infection” with a dermatophyte. The current thinking is that when the 
dermatophyte is present there is disease and when it is absent there is no disease.  
 
There are numerous antifungal drugs both oral and topical that in vitro are very potent and effective 
in inhibiting or even killing fungi. Despite these potent drugs the complete clinical and mycologic 
response rate in most clinical trials is well under 50%, most about 30%. It is not uncommon to see 
subjects who do respond, even complete clinical responses will still have positive cultures or 
microscopic evidence by KOH examination demonstrating the presence of a dermatophyte. There 
are also subjects with all of the signs and symptoms of disease from whom a dermatophyte cannot 
be cultured. 
 
The human epithelial surfaces of the skin, gut, genital tract, and respiratory tract are at the interface 
with the outside world. These areas have long been known to be inhabited by microorganisms 
previously referred to as “the normal flora” which for the most part was thought to neither 
contribute much to health or disease. But in recent years with the availability of DNA sequencing 
what had been called the normal flora is also called the microbiome. The DNA sequencing was 
needed to establish this because many of the organisms are either difficult or impossible to grow 
using routine culture techniques. It has become apparent that a normal microbiome can contribute 
to health while an abnormal microbiome can be associated with disease. An abnormal microbiome 
associated with disease is called a dysbiosis. 
 
Recent studies have focused in large part on the bacterial component of the cutaneous microbiome 
and little is known about the fungal component, the mycobiome. 
 
It is possible that the skin diseases of the foot associated with dermatophytes represent a dysbiosis 
rather than an “infection” in the traditional sense. It is known that using conventional culture 
techniques dermatophytes can be cultured from the feet of people with no signs or symptoms of 
skin disease. In addition, the diseases of the foot associated with dermatophytes are seen far more 
commonly in people who wear shoes than in people who are barefoot. 
 
It is possible that dermatophytes are in fact part of the cutaneous microbiome in at least some 
individuals. As part of the community of organisms that make up the cutaneous microbiome of the 
foot dermatophyte are kept in balance by other organisms such as bacteria. However, wearing 
shoes especially in warm climates and/or by people with sweaty feet changes the “micro climate” 
tipping the environmental condition to favor the dermatophyte resulting in the Tinea pedis and 
onychomycosis.  
 
Current antimicrobial treatments do nothing to correct a dysbiosis and may in fact contribute to 
the dysbiosis resulting in these conditions frequently being chronic recurrent. 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 15 of 41 
PROPRIETARY AND CONFIDENTIAL 
 
This is analogues to the better known vulvar vaginal candidiasis associated with uses of systemic 
antibiotics. A normal healthy vagina has a mixture of yeast and bacterial that keep each other in 
balance.  By taking an oral antibiotic that decreased the bacterial component thus favor the growth 
of yeast can result in vulvar vaginal candidiasis. 
 
It is also possible that subjects with the clinical features of disease who are culture and/or KOH 
negative may not be actually be false negative, but their disease could be associated with organisms 
other than the traditional dermatophytes or dermatophytes that are difficult if not impossible to 
culture with routine mycology cultures. There is a substantial literature implicating molds, yeast, 
and other organisms in these cases. Using DNA sequencing may more accurately characterize the 
community of organisms associated with these condition that has been accomplished to date with 
routine dermatophyte culture and KOH examinations. 
 
It is hoped that the topical probiotic DBI-001 will improve the treatment of common diseases of 
the skin and nails associated with dermatophytes. Assuming good safety and tolerability in this 
trial the sponsor will then enroll patients with T. pedis and onychomycosis into larger vehicle-
controlled efficacy trials. 
 
The purpose of the current protocol is to establish the safety and tolerability of a single application 
of 
 to the feet of patients with proven T. pedis. In addition, the effect of 
 on the 
T. pedis will also be evaluated. 
1.2 Rationale 
A single application of 
 to the skin of three different species of amphibians in two 
independent laboratories has been shown to treat and prevent a lethal cutaneous fungal infection.  
In-vitro 
 has been shown to significantly inhibit the growth of the fungus, T. rubrum 
most frequently associated with T. pedis. Based on these observations’ topical application of the 
probiotic 
 could treat T. pedis. This protocol intends to enroll only males because T. 
pedis is far more common in men than women. 
 
2. POTENTIAL RISKS AND BENEFITS 
2.1 Potential Risks 
Despite the fact that 
 is found in the cutaneous microbiome of some people as well as in 
the human food chain it is possible that application of 
 could result in a worsening of the 
T. pedis, impetigo, or cellulitis. A mild detergent solution will be used to collect samples and it 
could cause a local irritant reaction.  


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 16 of 41 
PROPRIETARY AND CONFIDENTIAL 
2.2 Potential Benefits 
In amphibians a single application of 
 has been shown to treat their cutaneous infection. 
It is possible that a single application of 
 could result in improvement even a clinical and 
microbiologic cure of the subject’s T. pedis. Upon subject’s study completion, subjects who 
continue to have signs and symptoms of T. pedis will be given an approved topical anti-fungal 
agent with application instructions. 
It should be noted that if worsening of the T. pedis, impetigo, or cellulitis were to occur, 
 
is susceptible to commonly used topical and oral antimicrobials and antibiotics. 
 
3. 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 
 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. 
 
4. STUDY DESIGN AND ENDPOINTS 
4.1 Description of the Study Design 
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 approximately 0.5 ml 
of the test article applied to each foot covering the web spaces of both feet as well as the plantar 
and lateral aspect of both feet as well as on and around all toes and toe nails. The three test articles 
will be 106 CFUs/ml, 107 CFUs/ml, and 108 CFUs/ml.  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. 
 
Evaluations will be followed according to Table 2 Schedule of Events for Subjects. At all 
evaluations, signs and symptoms of application site reactions (local tolerability at sites unaffected 
by T.pedis interdigital) will be recorded. At baseline, days 2, 3 (+1),7 (+/-1) ,14 (+/-2), and 28 (+/-
2), the signs and symptoms of T. pedis will be recorded. The investigators static global assessment 
(ISGA) of the interdigital T. pedis will be recorded at baseline, days 2, 3(+1) ,7 (+/-1) ,14 (+/-2), 
and 28 (+/-2). Subjects will also be queried for adverse events during their follow up visits or by 
self-reporting while on study until Day 28.  






 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 19 of 41 
PROPRIETARY AND CONFIDENTIAL 
5. 
Provisionally confirmed diagnosis at baseline by a positive potassium hydroxide (KOH) 
wet mount at the clinical site. 
6. 
The sum of the clinical signs and symptoms scores of the target lesion is at least 4, 
including a minimum score of at least 2 for erythema AND a minimum score of 2 for 
either scaling, fissures/ cracking or pruritus/burning (on a scale of 0-3, where 2 indicates 
moderate severity). 
6.2 Exclusion Criteria 
Subjects with the following will be excluded from this study: 
1. 
Any dermatological conditions that could interfere with clinical evaluations. 
2. 
Any underlying disease(s) or some other dermatological condition that requires the use 
of interfering topical or systemic therapy. 
3. 
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 
1 week 
Topical antibiotics on the affected area 
2 weeks 
Anti-inflammatories, corticosteroids, topical immunomodulators 
4 weeks 
 
4. 
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) 
4 weeks  
Antibiotics  
4 weeks 
Antifungal agents                                                                     
4 weeks 
Systemic immunomodulators 
4 weeks 
 
5. 
Treatment of any type for cancer within the last 6 months. 
6. 
History of any significant internal disease. 
7. 
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. 
8. 
AIDS or AIDS related complex by medical history 
9. 
Known or suspected immune suppressive medications or diseases 
10. 
Diabetes mellitus Type I or II by medical history 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 20 of 41 
PROPRIETARY AND CONFIDENTIAL 
11. 
Peripheral vascular disease based on medical history. 
12. 
Any subject not able to meet the study attendance requirements. 
13. 
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. 
 
6.3 Recruitment and Retention 
Subjects will be recruited from the Investigator’s clinical dermatology practice. The investigator 
may also recruit subjects using Ethics Committee approved recruitment materials. Retention is not 
anticipated to be an issue for this short 4-week trial. 
6.4 Withdrawal or Termination 
6.4.1 
Subject Withdrawal 
Participation in the study is strictly voluntary. A subject has the right to withdraw from the study 
at any time for any reason and is under no obligation to disclose the reason. If a subject withdraws, 
the Investigator and Sponsor are to be informed immediately and the withdrawal noted on the Case 
Report Form.  Subjects may be replaced at the discretion of the Investigator and Sponsor. 
 
The Investigator has the right to terminate participation of a subject at any time for any of the 
following: 
• 
Use of non-permitted concomitant medication 
• 
Lack of subject compliance 
• 
Protocol violation 
• 
Disease progression 
• 
Any perceived safety risks 
 
6.4.2 
Study Discontinuation 
There is only a single application per subject of the test article and drug product discontinuation is 
not anticipated. 
Study discontinuation is at the discretion of the Sponsor or the Investigator in any of, but not 
limited to, the following events: 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 21 of 41 
PROPRIETARY AND CONFIDENTIAL 
• 
Occurrence of unusual AEs in terms of their nature, severity, causality, duration, or 
unexpected incidence. 
• 
Medical or ethical reasons affecting the continued performance of the study. 
• 
Difficulties in the recruitment of the subjects. 
 
6.4.3 
Stopping Rules 
With a single application per subjects there is no need for stopping rules for individual subjects. 
However, the sponsor may terminate dosing new subjects if there are safety concerns noted for 
any reason. 
 






 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 24 of 41 
PROPRIETARY AND CONFIDENTIAL 
 
6.5 Study Visits 
The study will be conducted with a Screening visit that may also be Day 1 / Baseline visit, 1-hour 
after application evaluation and five follow-up visits.  Further details on timing, administration of 
the assessment, and processes are provided in the Study Operation Manual (SOM). 
 
6.5.1 
Screening Visit 
Following written informed consent from each subject, the Investigator will determine whether 
subjects are eligible to participate in the study by performing screening tests and evaluations. This 
would include collecting demographic information, review of Inclusion and Exclusion criteria, 
medical history, concomitant medications, a KOH examination at the site and ISGA. 
 
Screening and baseline visits can occur on the same day if no washout period is necessary. The 
baseline visit must be completed within 28 days of the screening visit. 
 
At the Screening visit, continuous monitoring of concomitant medications, therapies and AEs 
throughout the study period will begin. 
 
6.5.2 
All Other Visits 
Study visit assessments will be conducted as presented in Tables 2 and 3. 
 
a. Baseline (Day1) visit: 
For subjects who did not have a screening washout period will have the following tasks 
completed at baseline Day 1: 
1. 
Informed consent. 
2. 
Record demographics. 
3. 
Review of Inclusion/Exclusion Criteria. 
4. 
Medical history. 
5. 
Concomitant medication. 
6. 
T. pedis ISGA of each web space on both feet. 
7. 
T. pedis signs and symptoms. 
8. 
Classification toe web space. As not all web spaces are equally affected and the act of 
collecting samples from a web space could affect the laboratory results. Web spaces on 
both feet will be classified based on the ISGA as clear, almost clear, mild T. pedis, 
moderate T. pedis, severe T. pedis. In addition, one representative web space classified 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 25 of 41 
PROPRIETARY AND CONFIDENTIAL 
as moderate will be designated as the target sampling web space. Representative web 
space should be marked on each subject’s paperwork for reference. 
9. 
Signs and symptoms of local tolerability of the areas other than the web spaces.  
10. 
Collect sample for onsite KOH from the target sampling web space. 
11. 
Collect sample for reference mycology laboratory from the target sampling web space. 
12. 
Collect an e-swab from the target sampling web space. 
13. 
Obtain digital photograph of the target sampling web space. 
14. 
Assigned test article will then be applied to both feet. Approximately 0.5 ml of the test 
article will be applied to each foot spreading the test article over all web spaces, on and 
around all toe nails, the entire plantar and lateral aspects of the foot. 
15. 
Record any adverse event, if any. 
16. 
One hour after application of the test article, the following activities will be done: 
a. 
E-Swab from an affected web space other than target sampling web space.  
b. 
Signs and symptoms of local tolerability of the areas other than the web spaces. 
c. 
Record adverse event, if any. 
d. 
Give an appointment for Day 2 visit. 
 
 
For subjects who had a screening visit prior to a baseline visit before the test article is applied 
will have the following tasks completed: 
1. 
Review of Inclusion/Exclusion Criteria. 
2. 
Update Medical History. 
3. 
Concomitant medications. 
4. 
Record Adverse events, if any. 
5. 
T. pedis ISGA of each web space on both feet. 
6. 
T. pedis signs and symptoms. 
7. 
Classification toe web space. As not all web spaces are equally affected and the act of 
collecting samples from a web space could affect the laboratory results. Web spaces on 
both feet will be classified based on the ISGA at clear, almost clear, mild T. pedis, 
moderate T. pedis, severe T. pedis. In addition, one representative web space classified 
as moderate will be designated as the target sampling web space. 
8. 
Signs and symptoms of local tolerability of the areas other than the web spaces. 
9. 
Collect sample for reference mycology laboratory from the target sampling web space 
10. 
Collect an e-swab from the target sampling web space. 
11. 
Obtain digital photograph of the target sampling web space. 
12. 
Assigned test article will then be applied to both feet. Approximately 0.5 ml of the test 
article will be applied to each foot spreading the test article over all web spaces, on and 
around all toe nails, the entire plantar and lateral aspects of the foot  
13. 
One hour after application of the test article, the following activities will be done: 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 26 of 41 
PROPRIETARY AND CONFIDENTIAL 
a. 
E-Swab from an affected web space other than target sampling web space.  
b. 
Signs and symptoms of local tolerability of the areas other than the web spaces 
c. 
Record adverse event, if any. 
d. 
Given an appointment for Day 2 visit. 
 
Detailed instruction for sample collection and processing are in the Study Operation Manual, 
provided separately.  
 
Day 2 Approximately 24 hours after the test article was applied: 
1. 
Concomitant medications. 
2. 
Adverse events. 
3. 
T. pedis ISGA of each web space on both feet. 
4. 
T. pedis signs and symptoms. 
5. 
Signs and symptoms of local tolerability of the areas other than the web spaces.  
6. 
Collect an e-swab from an affected but previously not sampled web space. If none 
available collect e-swab from an unaffected but previously not sampled web space. 
7. 
Give subject appointment for Day 3 visit. 
 
Detailed instruction for sample collection and processing are in the Study Operation Manual, 
provided separately.  
 
Day 3 Approximately 48 hours after the test article was applied: 
1. 
Concomitant medications. 
2. 
Adverse events. 
3. 
T. pedis ISGA of each web space on both feet. 
4. 
T. pedis signs and symptoms. 
5. 
Signs and symptoms of local tolerability of the areas other than the web spaces.  
6. 
Collect an e-swab from an affected but previously not sampled web space. If none 
available collect e-swab from an unaffected but previously not sampled web space. 
 
Detailed instruction for sample collection and processing are in the Study Operation Manual, 
provided separately.  
 
Day 7 
1. 
Concomitant medications. 
2. 
Adverse events. 
3. 
T. pedis ISGA of each web space on both feet. 
4. 
T. pedis signs and symptoms. 
5. 
Signs and symptoms of local tolerability of the areas other than the web spaces.  


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 27 of 41 
PROPRIETARY AND CONFIDENTIAL 
6. 
Collect sample for routine mycology from the target sampling web space. 
7. 
Collect an e-swab from the target sampling web space. 
8. 
Obtain digital photograph of the target sampling web space. 
 
Detailed instruction for sample collection and processing are in the Study Operation Manual, 
provided separately.  
 
Day 14 
1. 
Concomitant medications. 
2. 
Adverse events. 
3. 
T. pedis ISGA of each web space on both feet. 
4. 
T. pedis signs and symptoms. 
5. 
Signs and symptoms of local tolerability of the areas other than the web spaces. 
6. 
Collect an e-swab from the target sampling web space. 
7. 
Obtain digital photograph of the target sampling web space. 
 
Detailed instruction for sample collection and processing are in the Study Operation Manual, 
provided separately.  
 
Day 28 
1. 
Concomitant medications. 
2. 
Adverse events. 
3. 
T. pedis ISGA of each web space on both feet. 
4. 
T. pedis signs and symptoms. 
5. 
Signs and symptoms of local tolerability of the areas other than the web spaces. 
6. 
Collect for routine mycology from the target sampling web space. 
7. 
Collect an e-swab from the target sampling web space. 
8. 
Obtain digital photograph of the target sampling web space. 
 
Detailed instruction for sample collection and processing are in the Study Operation Manual, 
provided separately.  
6.6  Study Specific Procedures 
6.6.1 
Grading of signs and symptoms of T. pedis 
Will be graded as follows: 
Fissuring/Cracking score: 
0=none        (complete absence), 
1=mild         (slight) 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 28 of 41 
PROPRIETARY AND CONFIDENTIAL 
2=moderate (definitely present) 
3=severe       (marked, intense) 
 
Erythema score: 
 0=none           (complete absence)  
 1=mild.          (slight), 
 2=moderate.   (definitely present) 
 3=severe         (marked, intense)  
 
Maceration score: 
0=none          (complete absence) 
1=mild          (slight) 
2=moderate   (definitely present) 
3=severe        (marked, intense) 
 
 Scaling score: 
 0=none         (complete absence) 
 1=mild          (slight) 
 2=moderate  (definitely present), 
 3=severe       (marked, intense)  
 
Pruritus score: 
0=none         (complete absence) 
1=mild           (slight) 
2=moderate   (definitely present) 
3=severe        (marked, intense)  
 
Burning/Stinging score: 
 0=none           (complete absence) 
 1=mild           (slight) 
 2=moderate     (definitely present),  
 3=severe         (marked, intense)  
             Composite (total) signs and symptoms score 
 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 29 of 41 
PROPRIETARY AND CONFIDENTIAL 
6.6.2 
T. pedis Investigator’s Static Global Assessment (ISGA) 
Clear -  
possible faint erythema and a hint of scale  
Almost clear - slight scale and minimal erythema 
Mild -  
definite scale and erythema but no maceration, cracking or fissuring 
Moderate - 
definite (mild to moderate) scale, erythema, maceration, and cracking or 
fissuring 
Severe -  
at least moderate or severe scale, erythema, maceration, and cracking or 
fissuring 
 
6.6.3 
Local Tolerability for Areas Not Affected by T. Pedis 
Local tolerability for areas to which the test article is to be applied but without T. pedis such as the 
unaffected web spaces on and around the toes, toe nails, the plantar and lateral aspects of the foot 
tolerability will be evaluated based on these signs and symptoms: 
 
Pain/Burning: as reported by the subject as being the greatest intensity they have experienced 
within the last 24 hours at Baseline or since the last visit at subsequent visits. 
0          None 
 
No pain/burning 
1          Mild            
Slight burning/stinging sensation; not really bothersome 
2          Moderate     
Definite warm, burning/stinging that is somewhat bothersome 
3          Severe         
Hot burning/stinging sensation that causes definite discomfort and  
                                                                   
may interrupt daily activities and/or sleep 
 
Pruritus: as reported by the subject as being the greatest intensity they have experienced within 
the last 24 hours at Baseline or since the last visit at subsequent visits. 
0          None                No pruritus 
1          Mild                 Slight pruritus, not really bothersome 
2          Moderate         Definite pruritus that is somewhat bothersome 
3          Severe              Intense pruritus that may interrupt daily activities and/or sleep 
  
Erythema: as assessed by the Investigator 
0          None 
 
No erythema present 
1          Mild 
 
Slight pink coloration 
2          Moderate 
Definite redness 
3          Severe  
Marked erythema, bright red to dusky dark red in color 
 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 30 of 41 
PROPRIETARY AND CONFIDENTIAL 
Edema: as assessed by the Investigator 
0          None 
 
No edema 
1          Mild 
 
Slight, but definite edema 
2          Moderate 
Definite edema 
3          Severe  
Marked edema 
 
Scabbing/Crusting: as assessed by the Investigator    
0          None 
 
No scabbing/crusting 
1          Mild 
 
Slight, but definite scabbing/crusting 
2          Moderate 
Definite scabbing/crusting 
3 
      Severe  
Marked scabbing/crusting 
 
6.6.4 
Sample Collection 
One representative web space, according to the grading of signs and symptoms of T. pedis, must 
be classified as at least moderate to be designated as the Target Sampling (or target lesion) web 
space. 
 
Subjects who have both feet affected, will have samples collected from each foot separately. 
Subjects that have one foot affected and the other foot unaffected, sample will only be collected 
from the affected foot.  Indicate on the CRF if samples were collected from Left and/or Right foot. 
 
     
For Microbial Sampling  
If one foot is moderate and the contralateral foot is less than moderate the less than moderate   
foot will also be sampled. 
For Drug Product Application  
Both feet are treated even if one foot is not affected 
 
Baseline Web space  
ISGA Grading 
Microbial Sampling 
Drug Product Application 
Clear 
No 
Yes 
Almost Clear 
Yes, if contralateral is moderate 
Yes 
Mild 
Yes, if contralateral is moderate 
Yes 
Moderate 
Yes 
Yes 
Severe 
Yes 
Yes 
 
 
 
 
 




 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 32 of 41 
PROPRIETARY AND CONFIDENTIAL 
6.7  Study Drug Product Administration 
All subjects will have a single application of their assigned test article applied by study personnel 
at the baseline visit. Details of test article preparation are in the Study Operation Manual, in brief, 
there is a vial with 
 in an aqueous gel vehicle. Then approximately 0.5 ml of the test 
article will be applied to each foot covering the toe web spaces, on and around the toe nails as well 
as the plantar and lateral aspects of the foot. The product will be allowed to air dry.  
6.8  Concomitant medication and Excluded Therapy 
Usage of prescription or over the counter topical or systemic medications will be reported during 
the subject’s participation in the study. The use of anti-fungal or antibacterial treatments in the 
past 4 weeks is an exclusion criterion. 
6.9  Investigational Product 
The test product will be applied by the Investigator or study personnel at the investigational site. 
Each subject will have a single application of approximately 0.5 ml of the test article applied to 
each foot. Both affected and unaffected feet will be treated covering the web spaces, toes, toe nails 
as well as the plantar and lateral aspect of both feet. The product is formulated as a suspension in 
a low viscosity aqueous gel. The three dose groups are: 
Cohort 1 dose 106 /ml CFUs of 
 
Cohort 2 dose 107/ml CFUs of 
 
Cohort 3 dose 108/ml CFUs of 
 
 
The cohort 1 dose is comparable to the dose that has been shown to be effective against cutaneous 
fungal infection of amphibians. It has been estimated that the density of bacteria on normal skin is 
approximately 1 x 105/cm2. At our highest dose of 108 CFUs/ ml applying 0.5 ml to each foot, this 
volume will cover approximately 500 cm2. The cohort 1, 2, and 3 doses then we would be adding 
103 CFUs ,104 CFUs, 105 CFUs / cm2, respectively. 
 
The doses in this trial are comparable to the doses used in the study of other topical live bacterial 
products. An ammonia oxidizing bacterium has been used in Phase 2 trials to treat acne at a dose 
of 109/ml (Aobiome Inc. patent #9738870), a coagulase-negative Staphylococcus at a dose of 
107/ml CFUs (Williams and Gallo 2017) has been used in atopic dermatitis patients, and a strain 
P. acnes has been applied to the face of acne patients at a dose of 108/ml CFUs. 
(https://www.clinicaltrials.gov/ct2/show/NCT03450369?term=Naked+Biome&rank=2). 
 
Each of the three groups will have 4 subjects. After the first cohort has completed their day 7 visits, 
if no significant tolerability or safety issues identified the second cohort will be enrolled. After the 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 33 of 41 
PROPRIETARY AND CONFIDENTIAL 
second cohort has completed the day 7 visits and if no significant tolerability of safety issues is 
identified the third cohort will be enrolled. 
6.10  Treatment Compliance 
All subjects will receive only a single application of the test article applied at the investigational 
site by designated study personnel. This will allow for well document compliance, Investigator or 
designee will record the time, date and dose of drug product administration. Data Analysis and 
Statistical Consideration. 
6.11  General Statistical Considerations 
As this is an open label safety and tolerability trial all of the collected data will be presented in 
listings, tables, and figures in a descriptive fashion. 
 
Primary Objective:  
Evaluate the safety and tolerability of DBI-001 in patients with Tinea pedis 
 
Secondary Objective:  
Evaluation of presence or persistence of 
 of DBI-001 following a single application of 
DBI-001. 
 
Effect of a single application of DBI-001 on the abundance of T. rubrum 
Effect of a single application of DBI-001 on the signs and symptoms of interdigital T. pedis. 
6.12  Analysis of Data for Objectives 
a. 
Primary Objective: Evaluation of presence or persistence of 
 following a single 
application of DBI-001. 
b. Secondary Objective: Effect of a single application of DBI-001 on the abundance of T. 
rubrum. 
c. 
Exploratory Objectives: Effect of a single application of DBI-001 on the signs and 
symptoms of interdigital T. pedis. 
6.13  Analysis Populations 
All subjects treated will be included in the analysis 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 34 of 41 
PROPRIETARY AND CONFIDENTIAL 
6.14  Sample Size Determination 
As there is no formal statistical analysis planned there were no assumption made in selection of 
the sample size. 
 
7. ASSESSMENT OF SAFETY 
7.1 Safety Evaluations and Criteria 
Upon completion of the day 7 visit by the first cohort, the Medical Monitor and Investigator will 
review the safety results and determine if the trial is to proceed with dosing the second cohort. The 
same process will be completed upon completion of Day 7 for Cohort 2 to determine if Cohort 3 
will be enrolled. 
 
As detailed in section 6.6.3, local tolerability will be evaluated by recording the severity of the 
signs of T. pedis as well as the signs and symptoms of local tolerability on treated areas not 
involved with T. pedis. In addition, adverse events will be documented. 
7.2 Adverse Event 
An AE is any untoward medical occurrence in a subject administered a pharmaceutical product, 
which does not necessarily have a causal relationship with the treatment.  An AE can be any 
unfavorable and unintended sign (e.g., including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of the study drug product, whether or not it is considered 
to be study drug product related.  This includes any newly occurring event or previous condition 
that has increased in severity or frequency since the administration of study drug product 
(treatment-emergent). 
7.3 Serious Adverse Event 
A serious adverse event (SAE) is any AE, occurring at any dose level and regardless of causality 
that: 
• 
Results in death. 
• 
Is life-threatening:  Life-threatening means that the subject was at immediate risk of death 
from the reaction as it occurred, (i.e., it does not include a reaction which hypothetically 
might have caused death had it occurred in a more severe form). 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization.  
• 
Results in persistent or significant disability/incapacity. 
• 
Is a congenital anomaly/birth defect. 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 35 of 41 
PROPRIETARY AND CONFIDENTIAL 
• 
Is an important medical event: an important medical event is an event that may not result in 
death, be life-threatening, or require hospitalization but may be considered an SAE when, 
based upon appropriate medical judgment, it may jeopardize the subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in the definitions for 
SAEs.  Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug abuse.   
• 
A hospitalization for an elective procedure will not be considered a SAE 
7.4 Unexpected Adverse Event 
An unexpected AE is an AE that is not reported in the Investigator’s Brochure (IB). 
7.5 Relationship of Adverse Events to Study Drug Product 
The following classifications should be used when evaluating the relationship of AEs and SAEs 
to the investigational drug product. 
1. None: No relationship between the experience and the administration of study drug product; 
related to other etiologies such as concomitant medications or subject’s clinical state. 
2. Unlikely: The current state of knowledge indicates that a relationship is unlikely.   
3. Possibly: A reaction that follows a plausible temporal sequence from administration of the 
study drug product and follows a known response pattern to the suspected study drug 
product.  The reaction might have been produced by the subject’s clinical state or other 
modes of therapy administered to the subject. 
4. Probably: A reaction that follows a plausible temporal sequence from administration of the 
study drug product and follows a known response pattern to the suspected study drug 
product.  The reaction cannot be reasonably explained by the known characteristics of the 
subject’s clinical state or other modes of therapy administered to the subject. 
5. Definitely: A reaction that follows a plausible temporal sequence from administration of the 
study drug product and follows a known response pattern to the suspected study drug product 
and can be confirmed with a positive re-challenge test or supporting laboratory data. 
 
Severity: 
1. 
Mild: Awareness of sign or symptom, but easily tolerated 
2. 
Moderate: Discomfort enough to cause interference with normal daily activities 
3. 
Severe: Inability to perform normal daily activities 
4. 
Life-threatening: Immediate risk of death from the reaction as it occurred 
 




 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 37 of 41 
PROPRIETARY AND CONFIDENTIAL 
9. SPECIAL REQUIREMENTS AND PROCEDURES 
9.1 Study Monitoring 
The Clinical Monitor and/or the Sponsor representative will arrange to visit the Investigator sites 
at regular intervals during the study.  The monitoring visits must be conducted according to the 
applicable International Conference on Harmonization (ICH) and Good Clinical Practice (GCP) 
guidelines to ensure protocol adherence, quality of data, drug accountability, compliance with 
regulatory requirements, and continued adequacy of the investigational site and its facilities. 
During these visits, eCRFs and other data related to the study will be reviewed and any 
discrepancies or omissions will be resolved.  The Clinical Monitor will be given access to study 
relevant source documents (including medical records) for purposes of source data verification. 
 
During and/or after completion of the study, quality assurance officers named by DermBiont or 
the regulatory authorities may wish to perform on-site audits.  The Investigator is expected to 
cooperate with any audit and aid and documentation (including source data) as requested. 
9.2 Audits and Inspections 
The Investigators and clinical sites will permit study related monitoring, audits, IRB/IEC review, 
and regulatory inspections as requested by FDA, DermBiont or designee, including direct access 
to source data/documents (i.e., original medical records, laboratory reports, hospital documents, 
progress reports, signed Informed Consent Forms (ICFs), etc.) in addition to eCRFs. 
9.3 Data Quality Control and Quality Assurance 
The Investigator is responsible for ensuring the study is conducted according to the protocol, Code 
of Federal Regulations (CFR), GCP, and applicable regulatory requirements. The responsibilities 
outlined in these documents along with the identification that a signed informed consent must be 
obtained prior to a subject participation in the study. 
9.4 Confidentiality 
To maintain subject privacy, all eCRFs, banked study samples, study drug accountability records, 
study reports and communications will identify the subject by the assigned subject identification 
number.  The Investigator will grant monitor(s) and auditor(s) from DermBiont or designee and 
regulatory authority(ies) access to the subject’s original medical records for verification of data 
gathered on the eCRFs and to audit the data collection process.  The subject’s confidentiality will 
be maintained and will not be made publicly available to the extent permitted by the applicable 
laws and regulations. 
 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 38 of 41 
PROPRIETARY AND CONFIDENTIAL 
All information regarding the investigational product supplied by DermBiont to the Investigator 
is privileged and confidential information.  The Investigator agrees to use this information to 
accomplish the study and will not use it for other purposes without consent from DermBiont Inc.  
It is understood that there is an obligation to provide DermBiont with complete data obtained 
during the study.  The information obtained from the clinical study will be used towards the 
development of the investigational product and may be disclosed to regulatory authority(ies), other 
Investigators, corporate partners, or consultants as required. 
9.5 Subject Rights 
Study subjects can withdraw their consent to have their clinical samples banked even after the 
sample has been shipped to the clinical laboratory. A study subject should contact their Investigator 
or the Investigator’s designee and ask for his/her sample to be withdrawn from the bank and 
destroyed. For samples that have been partially analyzed the remaining sample will be destroyed 
but the clinical site and DermBiont shall be entitled to retain and use any research results obtained 
prior to the withdrawal of consent. 
9.6 Protocol Amendments 
Protocol amendments that impact subject safety, change the scope of the investigation, or affect 
the scientific quality of the study must be approved by the IRB/IEC and submitted to the 
appropriate regulatory authorities before implementation of such modifications to the study. 
 
In the event that the protocol needs to be modified immediately to eliminate an apparent hazard to 
a subject, DermBiont will amend and implement the protocol change and subsequently notify the 
regulatory authorities and/or the IRB/IEC, as appropriate. 
 
The Investigator should not modify the protocol without agreement from DermBiont and prior 
review or approval by the IRB/IEC. Any deviations from the protocol should be documented by 
the Investigator or designee. 
9.7 Obligations of the Clinical Investigator 
The Investigator will agree to be responsible for the overall conduct of the study; for completing 
regulatory documents and documentation of training; for ensuring that the study is conducted 
according to the study protocol; for protecting the rights, safety and welfare of study subjects under 
their care; and for insuring data quality and integrity.  
 
If any study responsibilities are delegated, the Investigator will be responsible for maintaining 
written documentation of who is designate to perform the specific responsibilities.  


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 39 of 41 
PROPRIETARY AND CONFIDENTIAL 
 
The study will be conducted by qualified study Investigators.  
 
The Investigator or designees are responsible for qualified subjects and collecting samples. The 
Investigator or designees will be responsible for maintaining records of all samples collected and 
investigational drug administrations; recording the subject’s data on the source documents and 
eCRFs; documenting the presence of absence of AEs following sample collection and study drug 
applications and following the reporting requirements of any SAEs to the Sponsor and IRB/IEC.  
9.8 Institutional Review Board/Independent Ethics Committee 
The Investigator must obtain written IRB/IEC approval of the protocol, approval for relevant 
supporting information and all types of subject recruitment and advertisement and the ICF prior to 
starting the study.  The IRB/IEC will meet all US FDA requirements governing IRBs/IECs (21 
CFR Part 56). 
 
DermBiont or the designee must approve the ICF submitted to the investigational site’s IRB/IEC. 
All subject recruitment and advertisements must be submitted to DermBiont or designee prior to 
submission to the IRB/IEC, for review. 
9.9 Ethical Conduct of the Study 
DermBiont and the Investigator must comply with all instructions, regulations, and agreements in 
this protocol and in the applicable ICH and GCP guidelines and must also conduct the study in 
accordance with local regulations.   
9.10  Written Informed Consent 
Written informed consent is required from each subject prior to any testing under this protocol, 
including screening tests and evaluations.  The ICF, as specified by the investigational site’s 
IRB/IEC, must follow the Protection of Human Subjects regulations listed in 21 CFR Part 50.   
 
The background of the proposed study and the benefits and risks of the procedures and study must 
be explained to the subjects.  It is the responsibility of the Investigator to obtain consent and to 
provide the subject with a copy of the signed and dated ICF.  Confirmation of a subject’s informed 
consent must also be documented in the subject’s medical record prior to any testing under this 
protocol, including screening tests and evaluations. 
 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 40 of 41 
PROPRIETARY AND CONFIDENTIAL 
All ICFs used in this study must be approved by the appropriate IRB/IEC and by DermBiont or 
designee.  The ICF must not be altered without the prior agreement of the relevant IRB/IEC and 
DermBiont. 
9.11  Subject Data Protection 
Prior to any testing under this protocol, including screening tests and evaluations, subjects must 
authorize the release and use of protected health information (PHI), as required by local law. 
 
10. DATA HANDLING AND RETENTION OF RECORDS 
10.1 Paper and Electronic Case Report Form Completion 
Paper CRF and eCRFs will be completed for each enrolled subject.  It is the Investigator’s 
responsibility to ensure the accuracy, completeness, and timeliness of the data reported in the 
subject’s paper and eCRF.  Source documentation supporting the paper and eCRF data should 
indicate the subject’s participation in the study and should document the dates and details of study 
procedures, AEs, and subject status. 
 
Investigators will maintain copies of the paper CRF and eCRFs at the clinical site.  The paper CRF 
eCRFs will be completed as much as possible for subjects who discontinue or are terminated from 
the study by the investigator, and the reason for the discontinuation or termination must be clearly 
and concisely specified on the appropriate paper CRF and eCRF. 
10.2 Retention of Records 
The Investigator will maintain all study records according to ICH GCP and applicable regulatory 
requirements.  Records will be retained for at least 2 years after the last marketing application 
approval or 2 years after formal discontinuation of the clinical development of the investigational 
product or according to applicable regulatory requirements.  If the Investigator withdraws from 
the responsibility of keeping the study records, custody must be transferred to a person willing to 
accept the responsibility.  DermBiont must be notified in writing if a custodial change occurs. 
 
11. REFERENCES 
Kerry, R.G., Patra, J.K., Gouda. S., Park. Y., Shin.H.S., and Das.G 2018. Benefaction of probiotics 
for human health: A review. Journal of Food and Drug Analysis 26(3): 927-939. 
 
Leyden J.L. 1994: Tinea pedis pathophysiology and treatment: Journal of American Academic 
Dermatology, Sep:31(3pt 2): S31-3. 
 


 DermBiont® Inc. 
 
Protocol # DBI-201, V# 02, 05 Mar. 2019 
Page 41 of 41 
PROPRIETARY AND CONFIDENTIAL 
Anju S, Kumar NS, Krishnakumar B and Dileep Kumar BS (2015) Synergistic combination of 
violacein and azoles that leads to enhanced killing of major human pathogenic dermatophytic 
fungi Trichophyton rubrum. Front. Cell. Infect. Microbiol. 5:57. 
 
Matthew H. Becker, Robert M. Brucker, Christian R. Schwantes, Reid N. Harris, and Kevin P. 
C. Minbiole. The Bacterially Produced Metabolite Violacein Is Associated with Survival of 
Amphibians Infected with a Lethal Fungus. Appl. Environ. Microbiol. Oct 2009, 75 (21) 6635-
6638 
 
Harris 
R.N, Brucker 
R.M, Walke 
J.B, Becker 
M.H, Schwantes 
C.R, Flaherty 
D.C, Lam 
B.A, Woodhams D.C, Briggs C.J, Vredenburg V.T, and Minbiole K.P. Skin microbes on frogs 
prevent morbidity and mortality caused by a lethal skin fungus. ISME J. 2009 Jul;3(7):818-24. 
Doi: 10.1038/Ismej.2009.27. Epub 2009 Mar 26. 
                                                      
Teruaki Nakatsuji, Tiffany H. Chen, Saisindhu Narala, Kimberly A. Chun, Aimee M. Two, Tong 
Yun, Faiza Shafiq, Paul F. Kotol, Amina Bouslimani, Alexey V. Melnik, Haythem Latif, Ji-Nu 
Kim, Alexandre Lockhart, Keli Artis, Gloria David, Patricia Taylor, Joanne Streib, Pieter C.  
 
Dorrestein, 
Alex 
Grier, 
Steven 
R. 
Gill, 
Karsten 
Zengler, 
Tissa 
R. 
Hata, 
Donald Y. M. Leung, and Richard L. Gallo. Antimicrobials from human skin commensal bacteria 
protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci. Transl. Med. 9, 
eaah4680 (2017) 22 February 2017. 
 
Brucker, R. M., R. N. Harris, C. R. Schwantes, T. N. Gallaher, D. C. Flaherty, B. A. Lam, and K. 
P. Minbiole. 2008. 'Amphibian chemical defense: antifungal metabolites of the microsymbiont 
Janthinobacterium lividum on the salamander Plethodon cinereus', J Chem Ecol, 34: 1422-9. 
 
Williams, M. R., and R. L. Gallo. 2017. 'Evidence that Human Skin Microbiome Dysbiosis 
Promotes Atopic Dermatitis', J Invest Dermatol, 137: 2460-61.