A Randomized, Observer-Blinded, Within Patient Bilateral Comparison to Study the Safety and Efficacy of Daily Application for 4 Weeks of DBI-001 Gel Versus Aqueous Gel in Subjects With Atopic Dermatitis
Phase: PHASE2
Conditions: Atopic Dermatitis
Sponsor: DermBiont, Inc.

 
 
 
A Randomized, Observer-Blinded, within Subject Bilateral Comparison to 
Study the Safety and Efficacy of Daily Application for 4 weeks of DBI-001 Gel 
Versus Aqueous Gel in Subjects with Atopic Dermatitis 
 
 
 
 
 
 
 
 
 
NCT Number: NCT05253755 
 
 
 
 
 
 
 
 
 
Document Date: 12/16/2021 
 

 
Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
 
CLINICAL STUDY PROTOCOL 
 
 
Protocol Number: DBI-207 
 
A Randomized, Observer-Blinded, within Subject Bilateral Comparison to 
Study the Safety and Efficacy of Daily Application for 4 weeks of DBI-001 Gel 
Versus Aqueous Gel in Subjects with Atopic Dermatitis 
 
 
Investigational Product: 
DBI-001 
Development Phase of Study:   Phase 2 
US IND Number: 
26068 
Protocol: 
Supersedes 
Version 5.0 (16 December 2021) 
Version 4.0 (18 November 2021) 
Version 3.0 (11 April 2021) 
Version 2.0 (25 March 2021) 
Version 1.0 (17 July 2020) 
 
Sponsor:  
 
 
 
DermBiont, Inc. 
451 D Street, Suite 908 
Boston, MA 02210 
 
Primary Medical Monitor: 
 
Donald Chalfin, M.D., M.S., M.P.H. 
Senior Medical Director  
516-448-0047 
donald@dermbiont.com 
 
 
Secondary Medical Monitor: 
 
Emma Taylor, M.D. 
Chief Medical Officer 
626-260-1230 
emma@dermbiont.com 
 
 
 
 
 
 
Property of DermBiont, Inc. 
 
Confidential 
May not be used, divulged, published, or otherwise disclosed without the consent of 
DermBiont, Inc. 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
 
SPONSOR PROTOCOL REVIEW AND APPROVAL PAGE 
Review and approval by: 
Emma Taylor, M.D. 
Chief Medical Officer 
 
 
Signature 
 
 
 
 
 
 
 
Date 
Sanjay Jain, Ph.D.  
Chief Development Officer 
 
 
 
 
Signature 
 
 
 
 
 
 
 
Date 
Robert Brucker, Ph.D.  
Chief Scientific Officer 
 
 
 
Signature 
 
 
 
 
 
 
 
Date 
Donald Chalfin, M.D., M.S., 
M.P.H. 
Senior Medical Director 
 
 
 
 
Signature 
 
 
 
 
 
 
 
Date 
Martin Wong 
Vice President of Clinical 
Operations 
 
 
 
Signature 
 
 
 
 
 
 
 
Date 
Protocol Number: DBI-207 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
INVESTIGATOR AGREEMENT 
 
I have fully discussed the objectives of this study and the contents of this protocol with the 
sponsor’s representative. 
 
I understand that information contained in or pertaining to this protocol is confidential and 
should not be disclosed, other than to those directly involved in the execution or the ethical 
review of the study, without written authorization from the sponsor.  It is, however, permissible 
to provide information to a subject in order to obtain consent. 
 
I agree to conduct this study according to this protocol and to comply with its requirements, 
subject to ethical and safety considerations and guidelines, and to conduct the study in 
accordance with the Declaration of Helsinki, International Conference on Harmonisation 
guidelines on Good Clinical Practice (ICH E6), and applicable regional regulatory requirements. 
 
I agree to make available to sponsor personnel, their representatives and relevant regulatory 
authorities, my subjects’ study records in order to verify the data that I have entered into the case 
report forms.  I am aware of my responsibilities as a principal investigator as provided by the 
sponsor. 
 
I understand that the sponsor may decide to suspend or prematurely terminate the study at any 
time for whatever reason; such a decision will be communicated to me in writing.  Conversely, 
should I decide to withdraw from execution of the study, I will communicate my intention 
immediately in writing to the sponsor. 
 
 
_____________________________  
__________________________ 
Print Name 
 
 
 
 
Signature 
 
 
______________________________ 
__________________________ 
Title 
 
 
 
 
 
Date 
 
 
______________________________________________________________ 
Institution Name 
 
 
 
 
 
Signature on this page assures the sponsor that, to the best of the investigator’s knowledge, the affiliated 
Institutional Review Board/Independent Ethics Committee/Research Ethics Board (IRB/IEC/REB) operates 
in accordance with the governing regulations, and that the investigator understands, and agrees to abide by, 
all governing regulatory obligations and the International Council for Harmonisation (ICH) Guideline for 
Good Clinical Practice (GCP) and country and regional (local) requirements while conducting this clinical 
investigation. Additionally, investigator gives access to all relevant data and records to DermBiont monitors, 
auditors, DermBiont Clinical Quality Assurance representatives, designated agents of DermBiont, 
IRBs/IECs/REBs, and regulatory authorities as required. 
 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
TABLE OF CONTENTS 
 
SPONSOR PROTOCOL REVIEW AND APPROVAL PAGE ................................................. 2 
INVESTIGATOR AGREEMENT ................................................................................................. 3 
LIST OF TABLES ......................................................................................................................... 5 
LIST OF DEFINITIONS AND ABBREVIATIONS ................................................................... 6 
SYNOPSIS ...................................................................................................................................... 8 
1. 
INTRODUCTION ................................................................................................................ 19 
BACKGROUND INFORMATION ........................................................................................................................................ 19 
1.2 Rationale ..................................................................................................................................................... 20 
POTENTIAL RISKS AND BENEFITS ..................................................................................... 21 
POTENTIAL RISKS ........................................................................................................................................................ 21 
POTENTIAL BENEFITS ................................................................................................................................................... 21 
3. 
STUDY OBJECTIVES AND PURPOSE ........................................................................... 21 
STUDY DESIGN AND ENDPOINTS ........................................................................................ 21 
DESCRIPTION OF THE STUDY DESIGN ............................................................................................................................... 21 
STUDY ENDPOINTS ...................................................................................................................................................... 22 
4.2.1 Primary Endpoint ...................................................................................................................................... 22 
4.2.2 Secondary Endpoints ................................................................................................................................ 23 
INVESTIGATIONAL PRODUCT (IP) ...................................................................................... 23 
INVESTIGATIONAL PRODUCT AND AQUEOUS GEL (TEST ARTICLES) ........................................................................................ 23 
ELIGIBILTY CRITERIA ............................................................................................................ 23 
INCLUSION CRITERIA .................................................................................................................................................... 23 
EXCLUSION CRITERIA .................................................................................................................................................... 25 
RECRUITMENT AND RETENTION ..................................................................................................................................... 26 
WITHDRAWAL OR TERMINATION .................................................................................................................................... 26 
6.4.1 Subject Withdrawal .................................................................................................................................. 26 
6.4.2 Study Discontinuation .............................................................................................................................. 26 
6.4.3 Stopping Rules .......................................................................................................................................... 27 
STUDY VISITS ............................................................................................................................................................. 27 
6.5.1 Screening Visit .......................................................................................................................................... 27 
6.5.2 All Other Visits .......................................................................................................................................... 28 
STUDY SPECIFIC PROCEDURES ........................................................................................................................................ 33 
6.6.1 Grading of signs and symptoms of AD using ADSI .................................................................................... 33 
6.6.2 Local Tolerability ...................................................................................................................................... 34 
6.6.3 Sample Collection ..................................................................................................................................... 34 
TEST ARTICLE ADMINISTRATION ..................................................................................................................................... 35 
CONCOMITANT MEDICATION AND EXCLUDED THERAPY ....................................................................................................... 36 
RANDOMIZATION ........................................................................................................................................................ 36 
DATA ANALYSIS AND STATISTICAL CONSIDERATION. ................................................. 36 
GENERAL STATISTICAL CONSIDERATIONS .......................................................................................................................... 36 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
ANALYSIS OF EFFICACY DATA FOR OBJECTIVES .................................................................................................................. 37 
7.2.1 Primary Efficacy: ....................................................................................................................................... 37 
7.2.2 Secondary Efficacy: ................................................................................................................................... 37 
7.2.3 Exploratory Efficacy: ................................................................................................................................. 38 
7.3 ANALYSIS OF SAFETY DATA FOR OBJECTIVES ............................................................................................................... 38 
7.3.1 Local Tolerability ...................................................................................................................................... 38 
7.3.2 Adverse Events ......................................................................................................................................... 38 
7.4 ANALYSIS POPULATIONS ......................................................................................................................................... 39 
7.5 SAMPLE SIZE DETERMINATION ................................................................................................................................. 39 
4. 
ASSESSMENT OF SAFETY .............................................................................................. 39 
8.1 SAFETY EVALUATIONS AND CRITERIA ......................................................................................................................... 39 
8.2 ADVERSE EVENT .................................................................................................................................................... 39 
8.3 SERIOUS ADVERSE EVENT ........................................................................................................................................ 39 
8.4 UNEXPECTED ADVERSE EVENT ................................................................................................................................. 40 
8.5 RELATIONSHIP OF ADVERSE EVENTS TO INVESTIGATIONAL PRODUCT ................................................................................ 40 
PROCEDURES FOR ADVERSE EVENT RECORDING AND REPORTING ...................... 41 
EMERGENCY SPONSOR CONTACT ................................................................................................................................... 41 
OTHER REQUIRED SAFETY ASSESSMENTS ......................................................................................................................... 41 
SPECIAL REQUIREMENTS AND PROCEDURES ................................................................ 42 
STUDY MONITORING ................................................................................................................................................... 42 
AUDITS AND INSPECTIONS ............................................................................................................................................. 42 
DATA QUALITY CONTROL AND QUALITY ASSURANCE .......................................................................................................... 42 
CONFIDENTIALITY ........................................................................................................................................................ 43 
SUBJECT RIGHTS ......................................................................................................................................................... 43 
PROTOCOL AMENDMENTS ............................................................................................................................................ 43 
OBLIGATIONS OF THE CLINICAL INVESTIGATOR .................................................................................................................. 44 
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE ...................................................................................... 44 
ETHICAL CONDUCT OF THE STUDY .................................................................................................................................. 44 
WRITTEN INFORMED CONSENT ...................................................................................................................................... 45 
SUBJECT DATA PROTECTION .......................................................................................................................................... 45 
DATA HANDLING AND RETENTION OF RECORDS .......................................................... 45 
PAPER AND ELECTRONIC CASE REPORT FORM COMPLETION ................................................................................................ 45 
RETENTION OF RECORDS .............................................................................................................................................. 45 
REFERENCES ............................................................................................................................ 47 
 
LIST OF TABLES 
TABLE 1.   SCHEDULE OF EVENTS. ......................................................................................... 18 
TABLE 2. MICROBIOLOGICAL AND CYTOKINE PROFILING SAMPLES. ............................ 35 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
LIST OF DEFINITIONS AND ABBREVIATIONS 
TERM 
DEFINITION 
AD 
Atopic Dermatitis 
ADSI 
Atopic Dermatitis Severity Index  
AE 
Adverse Event 
Aqueous Gel 
Water made into a gel with a common gelling agent 
CFU 
Colony-forming unit, a unit used to estimate the number of viable 
bacteria or fungal cells in a sample 
CFR 
Code of Federal Regulations 
CRF / eCRF 
Case Report Form / electronic Case Report Form 
CSSSP 
Collection Sampling, Storage & Shipment Plan 
DBI-001 
Investigational Product, Study Drug- Janthinobacterium lividum 
Dermatophytes 
A pathogenic fungus that grows on skin, mucous membranes, hair, nails, 
feathers, and other body surfaces, causing ringworm and related diseases. 
DNA 
Deoxyribonucleic Acid 
Dysbiosis 
Microbial imbalance on or inside the body. 
Swab 
It is a liquid-based, multipurpose, collection and preservation system that 
maintains viability of aerobic, anaerobic and fastidious bacteria. 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
Genodermatoses 
Geno dermatoses are genetic diseases with cutaneous expression. 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
IEC 
Independent Ethics Committee 
ICH 
International Code of Harmonisation 
IRB 
Institutional Review Board 
IP 
Investigational Product 
LAR 
Legally Authorized Representative 
Microbiome 
Microorganisms in a particular environment  
MITT 
Modified intent to treat 
PBS 
Phosphate Buffered Saline 
PHI 
Protected Health Information  
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
qPCR 
Quantitative polymerase chain reaction 
RNA 
Ribonucleic Acid  
SAE 
Serious Adverse Event 
Sponsor 
DermBiont Inc. 
TEAEs 
Treatment-emergent Adverse Events  
Telemedicine 
An audiovisual communication that remotely connects investigators at 
site with subjects at home 
 
 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
SYNOPSIS 
NAME OF SPONSOR:  DermBiont Inc. 
 
NAME OF FINISHED PRODUCT: DBI-001 
 
NAME OF ACTIVE INGREDIENT(S): Janthinobacterium lividum (J. lividum) strain 
DB02473 
Title of Study 
A Randomized, Observer-blinded, Within Subject Bilateral Comparison to 
Study the Safety and Efficacy of Daily Application for 4 weeks of DBI-
001 Gel Vs. Aqueous Gel in Subjects with Atopic Dermatitis 
Investigator(s) 
TBD 
Study 
centre(s) 
Multiple centres 
Publication 
N/A 
Phase of 
development 
Phase 2b 
Objectives 
Primary Objective:  
 
• 
Effect of daily application of DBI-001 on the signs and symptoms 
of atopic dermatitis (AD). 
Secondary Objectives:  
• 
Determine the antibacterial effect of daily applications of DBI-001 
on the abundance of S. aureus in the cutaneous microbiome. 
• 
To determine the safety and tolerability of DBI-001 Gel vs. 
Aqueous Gel in subjects with AD. 
• 
Evaluation of the presence and persistence of strain DB02473 
following daily applications of DBI-001 for 4 weeks.  
• 
Characterize changes in abundance and diversity of the 
microbiome during and following 4 weeks of daily applications of 
DBI-001. 
• 
Characterize inflammatory cytokine profile before and after 
treatment with 4 weeks of daily applications of DBI-001. 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
Study Design 
and 
Evaluation 
Methods 
 
• 
A randomized, Observer-blinded, daily application, bilateral study 
of DBI-001 Gel vs. Aqueous Gel in subjects with AD. 
• 
Approximately 20 subjects will be enrolled with clinically stable 
AD according to the criteria of Hanifin and Rajkai with comparable 
anatomically symmetrical, bilateral target lesions (Hanifin and 
Rajka 1980). 
• 
Subjects meeting the inclusion/exclusion criteria will be enrolled 
into the study.  
• 
Subjects will be instructed to adhere to treatment site restrictions to 
avoid specific activities 12 hrs. prior to clinic visits and 12 hrs. after 
test article application that could adversely impact the quality of 
samples or remove the test articles from the treated sites. Showering 
or rinsing with water is acceptable. 
• 
Each subject will have 1 site identified on comparable anatomically 
symmetrical, bilateral areas spanning approximately 100 cm2, which 
is approximately the area of the palm of the hand. 
• 
Clinical evaluations of two sites of AD will be done by an 
evaluating investigator(s) who is blinded to treatment assignments.  
• 
The Atopic Dermatitis Severity Index (ADSI) (Van Leent et al. 
1998) is the sum of the severity scores of the signs and symptoms 
of AD including erythema, pruritus, exudation, excoriation and 
lichenification.   
• 
At Baseline (prior to test article application) and then at, Day 7 
(±2),14 (±2), 21 (±2), 28 (±2), 35 (±4) and 42 (±4), samples will be 
collected using PBS swabs for microbiologic evaluation from both 
treatment sites.  
• 
At Baseline (prior to test article application) and then again at the 
end of treatment, Day 28 (±2), samples for cytokine profiling will 
be collected from designated treatment sites using patches for 
cytokine profiling.  
• 
Both treated sites on all subjects will be treated with 27 daily doses 
(once daily application for 4 weeks) of the assigned test articles 
applied by study personnel at the baseline visit, Days 7 (±2),14 
(±2), and 21 (±2). Between visits on weekdays, subjects, or legally 
authorized representative (LAR), will apply the daily doses during 
telemedicine visits with a treating investigator, or qualified 
delegate. On weekends subjects or LAR will apply doses 
unsupervised. 
 
Methodology 
Observer-Blinded, Randomized, Aqueous Gel-Controlled, Bilateral 
Number of 
subjects 
Approximately 20 Subjects 
Study 
Population 
Males and females ages 12-65, in general good health with AD and 
comparable anatomically symmetrical bilateral AD lesions areas. 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
Inclusion 
Criteria 
 
Subjects must meet all of the following criteria to be included in the study: 
1. Ability to understand, agree to, and sign the study Informed 
Consent. If the subject is unable to provide consent for him/herself, 
the subject’s legally authorized representative may provide written 
consent. 
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 or Female Subjects of any race 12-65 years of age.  
4. Physician diagnosed clinically stable AD according to the criteria 
of Hanifin and Rajkaii  with comparable anatomically symmetrical, 
bilateral target lesions (Hanifin and Rajka 1980). Lesions must 
have an Atopic Dermatitis Severity Index (ADSI) ≥6. The two sites 
need to be comparable anatomically symmetrical sites. It will be in 
the opinion of the Investigator based on subject’s medical history 
whether the lesions are clinically stable. 
5. Female subjects of child-bearing potential must use at least one 
method of birth control that results in a low failure rate (i.e., less 
than 1% per year) when used consistently and correctly such as 
implants, injectables, combined oral contraceptives, 
some intrauterine devices (IUDs), sexual abstinence or 
vasectomized partner for the duration of study participation. 
6. Technical ability and willingness to self-apply, or LAR to apply, 
test articles during telemed visits with the study staff and 
unsupervised on weekends. 
7. Willingness to discontinue use of systemic AD treatments and 
topical treatments to the target areas for the duration of the study 
unless specifically permitted by the Investigator.  
8. Willingness to comply with test site restriction for 12 hours prior to 
all office visits including the Baseline visit and for 12 hours after 
each treatment application. These treatment site restrictions include: 
a. 
No washing of test sites with any cleansers or soaps at any 
time from the Baseline visit to completion of the Day 42 
Follow up Visit. Water passing over the areas during 
showering is acceptable. 
b. No rubbing the test sites with a washcloth, towel, luffas. Pat 
dry after showering is acceptable. 
c. 
No recreational activities in chlorinated or chemically treated 
water such as swimming pools, hot tubs, and spas. 
d. No tight or form fitting clothing covering the treatment areas. 
e. 
No sunbathing or use of suntan parlors or tanning beds. 
f. 
If participating in physical activities resulting in heavy 
perspiration only pat dry test site areas with towel if needed. 
g. Any activity that in the opinion of the investigator might alter 
the quality of the samples collected or risk removal of the 
test article. 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
9. Willingness to undergo the following washout periods: 
a. 
Washout of 2 weeks prior to the Baseline visit for topical 
treatments used on the two treatment target sites, including 
but not limited to: antibacterial products, anti-
inflammatories (e.g., corticosteroids, tacrolimus, 
Pimecrolimus). Other than the two treatment sites, topical 
medications may be used before/during the duration of the 
study. Subjects will be provided 1% hydrocortisone for 
treating non-target areas during the trial. 
b. Washout of 4 weeks prior to the Baseline visit for systemic 
treatments for AD, including but not limited to 
corticosteroids (oral or intramuscular injections), systemic 
immunomodulators or immunosuppressive agents (e.g., 
methotrexate, cyclosporine, hydroxychloroquine), 
antibiotics (oral or injected, if required to treat a medical 
condition short duration of oral antibiotics (≤10 days) are 
permitted after randomization) 
c. 
Washout of 2 weeks prior to the Baseline visit for bleach 
baths. 
d. Washout of 2 weeks prior to the Baseline visit for 
phototherapy. 
10. No history of allergy to at least two of the following classes of 
antibiotics: 
Cephalosporins, Quinolones, Tetracyclines, Aminoglycosides 
Macrolides, Carbapenems and Lipopeptides. 
11. Willingness to allow digital photos of treatment areas to be taken 
and stored. 
 
Exclusion 
Criteria 
1. Women who are pregnant, planning a pregnancy, breastfeeding or 
have a positive pregnancy test at screening. 
2. Any dermatological conditions that could interfere with clinical 
evaluations or any disease state or physical condition which might 
expose the subject to an unacceptable risk by study participation. 
3. Any underlying disease(s) or other dermatological conditions that 
require the use of exclusionary topical or systemic therapy.  
4. Spontaneously improving or rapidly deteriorating dermatitis 
anywhere on the body. 
5. Netherton’s syndrome or other genetic dermatoses that result in 
defective epidermal barrier function. 
6. Treatment of any type of cancer within the last 6 months other than 
cutaneous basal cell carcinoma. 
7. History of any significant internal disease (which contraindicates 
use of live microbiome e.g., leukemia, liver failure, cardiovascular 
disease). 
8. 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 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
hypersensitivity or allergic reactions to any of the study 
preparations as described in the Investigator’s Brochure. 
9. AIDS or AIDS related complex by medical history. 
10. Known or suspected immune suppressive medications or diseases 
or any condition that in the opinion of the investigator would 
increase the subject’s susceptibility to opportunistic infections. 
11. Treatment with systemic immune modulating or anti-inflammatory 
biologic agents within 16 weeks of Baseline Visit. 
12. Poorly controlled diabetes mellitus Type I or II by medical history. 
13. Peripheral vascular disease based on medical history. 
14. Any subject not able to meet the study attendance and telemed visit 
requirements. 
15. Participants with a history of psychiatric disease or history of 
alcohol or drug abuse that would interfere with the ability to 
comply with the study protocol. 
16. 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 articles will be applied by designated unblinded treating 
investigator(s) at respective the investigational site(s) on Baseline/Day 1 
followed by weekly applications on Days 7 (+/-2), 14 (+/-2), and 21 (+/-2).) 
The daily applications between visits will be applied by the subjects, or 
LAR, under the supervision of a designated treating investigator(s), or 
delegate(s), during a telemed visit on weekdays and unsupervised on 
weekends. 
 
Approximately 0.1ml of the assigned test articles will be applied to 
designated treatment sites. 
 
1mL vial of DBI-001 gel contains 107-109 CFU/mL of DB02473. 
Approximately 0.1mL applied to a treatment area that is approximately 100 
cm2 will contain approximately 104-6 CFU per cm2 of DB02473. 
 
Duration of 
Trial 
Approximately 56 days (+/-4) including up to 14 days from Screening 
Visit to Baseline Visit, a 28 (+/-2) day treatment period followed by a 14 
(+/-4) day post treatment follow up.   
 
Statistical 
methods 
All subjects who are randomized and treated with test article will be 
included in the Intent-to-Treat analysis set.  
 
All subjects who are randomized, receive at least one (1) confirmed dose 
of test article, and have at least one (1) post-baseline safety assessment 
will be included in the Safety analysis set. 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
The evaluation of S. aureus qPCR and CFU abundance will be performed 
on all subjects and separately in a modified intent to treat (MITT) 
population defined as subjects with bilateral abundant S. aureus at baseline 
as detected by qPCR. 
 
A MITT population defined as all subjects with DB02473 detected by 
qPCR at one or more time points in samples obtained from one treatment 
targeted site but no DB02473 detected in any sample from the contralateral 
treatment targeted site at any time point during the trial will also be 
evaluated. 
 
Linear interpolation of efficacy variables will be performed using observed 
data that precedes and follows the off-schedule visit, if present. The last 
observation will be carried forward if all the data subsequent to the off-
schedule value is missing. 
 
No adjustments for multiplicity will be made; p-values are primarily 
presented for descriptive purposes. 
 
Safety 
Evaluation 
Tolerability will be evaluated through assessment of the severity of the 
signs and symptoms of the disease state (erythema, pruritus, exudation, 
excoriation and lichenification) as well as pain, burning, or stinging and 
review of adverse events. Any local skin reaction that requires use of a 
concomitant therapy or study discontinuation should be reported as an AE 
on the Case Report Forms (CRFs).  
 
Sample Size 
Sample size is based on clinical judgement and published literature on this 
type of trial and is deemed adequate to successfully demonstrate the stated 
goals. 
 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
Study Endpoints 
Primary Study Endpoint: 
The hypothesis of this trial related to clinical effect is that 4 weeks 
of daily dosing with DBI-001 will improve AD based on 
evaluation of signs and symptoms of AD in the comparison of 
sites treated with DBI-001 DP or Aqueous Gel on the following: 
 
• 
Change from baseline in ADSI score at days 7 (±2), 14 (±2), 21 
(±2), 28 (±2), 35 (±4) and 42 (±2). 
• 
Change from baseline in individual signs and symptoms of AD 
(components of ADSI score) at days, 7 (±2), 14 (±2), 21 (±2), 28 
(±2) 35 (±4) and 42 (±2). 
 
Secondary Endpoints: 
 
In the S. aureus MITT population, comparison of sites treated 
with DBI-001 or Aqueous Gel on the following microbial metrics: 
 
• 
Change from baseline in signs and symptoms of local tolerability 
(erythema, pruritus, exudation, excoriation and lichenification as 
well as pain, burning or stinging) for the DBI-001-treated sites vs. 
the Aqueous Gel-treated sites. 
• 
Change from baseline in abundance of S. aureus based on   
molecular diagnostic qPCR on samples obtained from lesioned 
skin at days 7, 14, 21, 28, 35 and 42. 
• 
Change from baseline in abundance of S. aureus based on CFU 
counts on samples obtained from lesioned skin at days 7, 14, 21, 
28, 35, and 42. 
• 
The proportion of subjects with a greater decrease in ADSI for the 
DBI-001-treated site than the Aqueous Gel-treated site. 
• 
Changes in the abundance and diversity of the microbiome for the 
DBI-001-treated sites vs. the Aqueous Gel-treated sites. 
• 
Changes in inflammatory cytokine profile before and after 
treatment with 4 weeks of daily applications of DBI-001. 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
Analysis of Efficacy 
Primary:  
The primary analysis will compare the differences from baseline in 
ADSI score between DBI-001 and Aqueous Gel treated sites will 
be done using a two-sided Wilcoxon sign rank test at each of Days 
7, 14, 21, 28, 35 and 42.  
 
The proportion of subjects with a greater decrease in ADSI for the 
DBI-001-treated sites than the Aqueous Gel-treated sites will be 
summarized descriptively for Days, 7, 14, 21, 28, 35, and 42. 
 
Comparison of differences at Day 28 between DBI-001 and 
Aqueous Gel of abundance of DB02473 on treated sites will be 
done using a two-sided Wilcoxon sign rank test.  
 
Comparison of differences at Day 28 between DBI-001 and 
Aqueous Gel of abundance and diversity of the microbiome based 
on DNA sequencing will be done using a two-sided Wilcoxon sign 
rank test. 
 
Comparisons at Days 7, 14, 21, 35, and 42 will also be done.  
 
Additionally, a repeated measures model will be used to compare 
DBI-001 to Aqueous Gel for the secondary endpoints. P-values will 
be provided for descriptive purposes. 
 
Secondary: 
The secondary analysis of the S. aureus MITT population will 
compare the differences in change from baseline and Day 28 
between DBI-001 and Aqueous Gel treated sites in abundance of S. 
aureus based on qPCR and CFU counts using a 2-sided Wilcoxon 
sign rank test, alpha = 0.05, with a null hypothesis of median 
difference equal to zero.  
 
Comparisons at Days 7, 14, 21, 35, and 42 will also be done. 
 
Additionally, a repeated measures model will be used to compare 
DBI-001 to Aqueous Gel for the secondary endpoint. P-values will 
be provided for descriptive purposes. Changes in inflammatory 
cytokine profile before and after treatment with 4 weeks of daily 
applications of DBI-001. 
 
Exploratory: 
Comparison in changes in the overall microbiome as defined by 16s 
and/or whole genome sequencing of samples obtained prior to, 
during, and after treatment. 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
Comparison of change from baseline in individual signs and 
symptoms of AD (components of ADSI score) between DBI-001 
and Aqueous Gel treated sites will be done using a two-sided sign 
test at each of Days 7, 14, 21, 28, 35, and 42. 
 
Additionally, a repeated measures model will be used to compare 
DBI-001 Gel to Aqueous Gel for the above exploratory endpoints. 
Analysis of Safety 
Signs and symptoms of local tolerability (erythema, pruritus, 
exudation, excoriation and lichenification as well as pain, burning, 
or stinging) will be summarized with changes from baseline. 
 
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, seriousness, action taken 
regarding the investigational product, corrective treatment, outcome, 
and Investigator’s assessment of causality. All reported treatment-
emergent AEs (TEAEs), defined as any AE with an onset on or after 
the date of first investigational product application, will be 
summarized by treatment group, the number of subjects reporting 
TEAEs, 
system 
organ 
class, 
preferred 
term, 
severity, 
and 
relationship to investigational product. When summarizing TEAEs 
by severity or relationship to investigational product, each subject 
will be counted only once within a system organ class or a preferred 
term using the event with the greatest severity or causality, 
respectively, within each category. All reported serious adverse 
events (SAEs) will be summarized by treatment group, the number 
of subjects reporting SAEs, system organ class, preferred term, 
severity, and relationship to investigational product. 
 
All information pertaining to AEs noted during the study will be 
listed by subject and will include a verbatim description of the event 
as reported by the Investigator, as well as the preferred term, system 
organ class, start date, stop date (if stopped), seriousness, severity, 
action taken regarding the investigational product, corrective 
treatment, outcome and relationship to the investigational product. 
In addition, a listing of subjects who prematurely discontinue from 
the study due to AEs will be provided as well as a listing of subjects 
who reported an SAE. 
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. 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
Study Design/Type 
 
This is a randomized, observer blinded, Aqueous Gel-controlled, 
daily application for 4 weeks, within-subject, bilateral comparison 
trial examining the effect of DBI-001 Gel vs. Aqueous Gel on the 
clinical ADSI scores and the abundance of S. aureus of comparable 
bilateral target sites of AD as well as signs and symptoms of local 
tolerability on treated sites in subjects. 
 
Subjects meeting the inclusion/exclusion criteria and having moderate 
to severe AD lesions at screening and baseline/Day 1 will be enrolled 
into the study.  
 
In an observer-blinded fashion, each subject will have two sites 
randomly assigned to have either DBI-001Gel or Aqueous Gel 
applied to the designated treatment targeted sites.  
 
After Screening, Study visits will occur at Day 1 Baseline then Days 
7 (±2), 14 (±2), 21 (±2), 28 (±2), 35 (±4), and 42 (±4). 
 
At each study visit, the following procedures will be conducted: 
clinical assessment of signs and symptoms of AD, ADSI clinical 
scoring, clinical signs and symptoms of erythema, pruritus, 
exudation, excoriation, lichenification. pain, burning, or stinging, 
and collection of microbiologic samples. At baseline prior to test 
article application and at the Day 28 (±2) visit samples for cytokine 
profiling will be collected. Photos of both treatment sites will be 
taken on all visits except the Screening Visit. 
 
 
 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
Table 1.   Schedule of Events. 
Evaluation 
aScreen 
(- 14 Day 
to day 0) 
Day 1  
Baseline  
Day 7 
(±2) 
Day 14 
(±2) 
Day 21 
(±2) 
Day 28 
(±2) 
Day 35 
(±2) 
Day 42 
(±4) 
 
Treatment 
Follow-up 
Demographics 
X 
  
  
  
  
  
  
  
Inclusion/Exclusion 
X 
 
  
  
  
  
  
  
Urine Pregnancy test (For 
Women of childbearing 
potential) 
X 
 
  
X 
  
 
  
X 
Confirm Compliance with 
Treatment Site Restrictionsb 
  
X 
X 
X 
X 
X 
X 
X 
Medical History 
X 
  
  
  
  
  
  
  
Concomitant Medication 
Query 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Assessment of Local 
Tolerability 
 
Xc 
X 
X 
X 
X 
X 
X 
Calculate ADSI Scores based 
on Signs and Symptoms of 
AD 
X 
X 
X  
 X 
 X 
 X 
X 
 X 
Digital Images of Both 
Treatment Sites 
  
X 
X 
X 
X 
X 
X 
X 
PBS Swabs from both Sites 
  
X 
X 
X 
X 
X 
X 
X 
 Sample both Sites for 
cytokine profiling  
  
X 
  
  
  
X 
  
  
Apply Test Articles After all 
Evaluations and Sampling 
  
X 
 X  
  X 
  X 
  
  
  
Collect Returned Used and 
Unused Test Articles 
  
  
 X 
 X 
 X 
X 
  
  
Dispense Test Articles for 
Home Application 
  
X 
 X 
X 
X 
  
  
  
Review Treatment Site 
Restrictions 
  
X 
 X 
X 
X 
  
  
  
Review Procedures for 
Telemed Visits 
  
X 
  
  
  
  
  
  
Dispense 1% Hydrocortisone 
Ointment as Needed 
  
X 
X  
 X 
 X 
X  
X  
X  
Appointment for Next Clinic 
Visit and Telemeda Visits 
Xa  
X 
X 
X 
X 
X 
X 
  
 
a Screening and Baseline visits can be on the same day only if all eligibility criteria are met and all required Screening and Day 
1/Baseline tests and tasks are completed on the same day. 
b Except for the Day 28, 35, or 42 visits, if violations of treatment site restrictions prior to the visit are reported, details of the 
violation should be recorded in the CRF and the visit should be completed including evaluations and sampling.  
c On Baseline/Day 1, local tolerability is to be assessed  30-minutes after application of test articles. 
For the Day 28, 35, and 42 Visits: 
If violations of treatment site restrictions reported occurred more than 24 hours prior to the visit at the Day 28, 35, or 42 visits, 
details of the violation should be recorded in the CRF and the evaluations and sampling completed as scheduled. 
If violations of treatment site restrictions less than 24 hours prior to the visit is reported at the Day 28, 35, or 42 visits, details of 
the violation should be recorded in the CRF. Evaluations can be completed but an additional visit 24-48 hours after the violation 
should be scheduled for sample collections. 
Details on sampling sites are in Table 2 and the Collection Sampling, Storage, Shipping Procedure, provided separately. 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
1. INTRODUCTION 
Background Information 
DBI-001 is a topical live bacterial product containing Janthinobacterium lividum (a strain isolated 
from humans, DB02473). This product is being developed as a topical probiotic for the treatment 
of diseases of the skin. DB02473 is an aerobic Gram-negative bacterium commonly found in the 
soil, water, vegetables and grains from the human food chain (Asakura et al. 2016; DR001 2019; 
DR002 2019) and on the skin of healthy humans (DR001 2019; DR002 2019). The strain of 
DB02473 is a strain that DermBiont isolated from the skin of a healthy young adult. Based on c  
DNA sequencing, this strain has no known virulence factors nor genes that would indicate 
antimicrobial resistance.  In vitro, the DB02473 strain has been shown to inhibit the growth of S. 
aureus and dermatophytes. This strain is sensitive to commonly used antibiotics. 
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 not thought to contribute 
to health or disease. In recent years, enabled by the availability of DNA sequencing, what had been 
called the normal flora is now called the microbiome.  DNA sequencing is able to detect the many 
organisms that are either difficult or impossible to grow using routine culturing techniques. A 
normal microbiome can contribute to health while an abnormal microbiome, a dysbiosis, can be 
associated with disease.  
 
Atopic dermatitis (AD) is a common skin disease that affects a large proportion of the adult and 
pediatric population worldwide.  S. aureus presence in the cutaneous microbiome of AD patients 
has been directly correlated to disease severity (Blazewicz et al. 2017; Hepburn et al. 2017). In the 
case of S. aureus and AD, it now appears this is not an “infection” in the traditional sense, but 
rather a dysbiosis characterized by decreased overall diversity of organisms and a high abundance 
of S. aureus. It has been hypothesized that in subjects without AD, the commensal bacteria in the 
microbiome contribute to host defense by producing metabolites that can control the abundance of 
S. aureus. The dysbiosis seen in AD may be functionally important because of a loss of these 
protective strains as well as the AD patient’s deficiency in host produced antimicrobial peptides. 
Several different bacterial species on healthy human skin produce anti–S. aureus activity and 
bacteria with this activity were far less frequent on the skin of AD patients. The application of 
antimicrobial Coagulase Negative Staphylococci (CoNS) strains to animal or human skin greatly 
reduced S. aureus abundance. Together, these observations show that specific bacteria within the 
human skin microbiome defend against an overabundance of S. aureus (Nakatsuji et al. 2017; 
Williams and Gallo 2017). 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
Application of DB02473 to the skin of amphibians has been shown to treat and prevent the 
acquisition of a lethal cutaneous fungal infection. (Harris et al. 2009). The exact mechanism by 
which DB02473 inhibits the growth of bacteria, fungi and other microorganisms is not yet known. 
It is known that DB02473 produces some metabolites that have antimicrobial activity. These 
compounds are violacein, indol-3-carboxaldehyde, and Janthinocins. 
 
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 at a dose of 
109 CFUs/ml (US9738870B2 2017). In addition, a coagulase-negative Staphylococcus strain at a 
dose of 107CFUs/ml (Williams and Gallo 2017) has been used in atopic dermatitis patients, and a 
strain of P. acne has been applied to the face of acne patients at a dose of 108CFUs/ml 
(Naked_Biome:NCT03450369 2018). In addition, the sponsor has completed clinical trials with 
DBI001 in patients with AD (DBI-CSR-203) and T. pedis (DBI-CSR-201, DBI-CSR-204) . 
 
The Sponsor believes that it is possible that the application of DBI-001 to the skin of patients with 
AD will decrease the abundance of S. aureus resulting in an improvement in the signs and 
symptoms of AD. This therapeutic approach would have the potential to decrease the use of oral 
and topical antibiotics. 
 
The purpose of the current protocol is to investigate the effect of DB02473 on the signs and 
symptoms of AD. In addition, the safety, tolerability and efficacy of daily application of DB02473 
to the skin of AD subjects will be evaluated as will the effect of DB02473 on the abundance of S. 
aureus. 
 
1.2 Rationale 
In-vitro DB02473 has been shown to significantly inhibit the growth of S. aureus (DR005 2019)    
most frequently associated with AD. Application of DB02473 to the skin of amphibians has been 
shown to be able to treat and prevent the acquisition of a lethal cutaneous fungal infection. (Harris 
et al. 2009). In a previous small pilot clinical trial, a single application of DBI001 was well 
tolerated and resulted in the reduction in the abundance of S. aureus and improvement in the signs 
and symptoms of AD, most noticeable pruritis (DBI-CSR-203). In a clinical trial of subjects with 
T. pedis 28 daily applications of DBI001 to the entire foot was well tolerated, decreased the 
abundance of T. rubrum, and improved the signs and symptoms of T. pedis. (DBI-CSR-201, DBI-
CSR-204) Based on these observations, topical application of the probiotic DB02473 has the 
potential to be a novel approach to the treatment of AD. 
 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
POTENTIAL RISKS AND BENEFITS 
Potential Risks 
Despite the fact that DB02473 is found in the cutaneous microbiome of some people as well as in 
the human food chain, it is possible that application of DB02473 could result in a worsening of the 
AD, impetigo, folliculitis, or cellulitis. It is possible that DB02473 could be an opportunistic 
pathogen in severely immune compromised subjects. PBS solution will be used to collect samples 
and it could cause a local irritant reaction as could the sample collection method used for cytokine 
profiling.  
 
As detailed in the Investigator’s Brochure, if worsening of the AD, impetigo, or folliculitis or 
cellulitis were to occur, DB02473 is susceptible to commonly used topical and oral antimicrobials 
and antibiotics. 
Potential Benefits 
It is possible that daily applications of DB02473 could result in improvement in the subject’s AD. 
Such a treatment also has the potential to decrease the use of oral and topical antibiotics. 
3. STUDY OBJECTIVES AND PURPOSE 
The purpose of the study is to evaluate the effect of 27 daily applications of DBI-001 on the signs 
and symptoms of active AD, and the safety and tolerability of DBI-001 in subjects with active AD. 
Secondly, to see the effect of this treatment on the abundance of S. aureus. Thirdly to evaluate the 
presence or persistence of DB02473 and the impact on the overall microbiome following once 
daily application of DBI-001 for 4 weeks.  
STUDY DESIGN AND ENDPOINTS 
Description of the Study Design 
This is a randomized, observer blinded, Aqueous Gel-controlled, once daily application for 27 
days within-subject, bilateral comparison trial examining the effect of DBI-001 Gel vs. Aqueous 
Gel. Approximately 20 subjects will be enrolled. Women of childbearing potential will be tested 
for pregnancy with urine pregnancy test. Women who are pregnant or who have a positive 
pregnancy test will be excluded from the study. At each investigative site there will be two types 
of investigators: treating investigators and evaluating or observing investigators. The treating 
investigator(s), or delegate(s), will apply the treatments and be unblinded to treatment assignment. 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
The observing or evaluating investigator(s) will be blinded to treatment assignment and perform 
all clinical evaluations. 
 
Subjects meeting the inclusion/exclusion criteria will be enrolled into the study. Each subject’s 
comparable anatomically symmetrical, bilateral treatment sites will be randomly assigned to be 
treated with either DBI-001 or the Aqueous Gel control. Treatments will be applied in the clinic 
by a treating investigator, or designee. On weekdays at home, the subjects, or LAR,  will apply 
under the supervision (by telemed) of a treating investigator, or delegate(s), and unsupervised (no 
telemed visit) on weekends. Clinical evaluations will be made by a blinded-to-treatment evaluating 
investigator who will grade the severity of signs and symptoms of AD (erythema, pruritus, 
exudation, excoriation and lichenification) to calculate the ADSI score and local tolerability, which 
will also include assessment of the severity of pain, burning, or stinging as reported by subjects. 
Samples for microbiology will be tested by qPCR for the presence and abundance of DB02473 
and S. aureus, 16s and/or whole genome sequencing will be used to characterize the entire 
microbiome. Samples will also be cultured for S. aureus CFU counts and for the presence of 
DB02473. Additionally, samples will be obtained to characterize cytokine profiles. 
After Screening, study visits will occur at Day 1 Baseline (may be combined with Screening), 
Days 7 (±2), 14 (±2), 21 (±2), 28 (±2), 35 (±4), and 42 (±4). At each study visit, the following 
procedures will be conducted: clinical assessment of the severity of the signs and symptoms of AD 
(erythema, pruritus, exudation, excoriation and lichenification) and the severity of local tolerability 
(pain, burning, or stinging) as reported by subjects in addition to erythema, pruritus, exudation, 
excoriation, and lichenification. Samples will be collected for microbiologic testing and cytokine 
profiling. Subjects will be instructed on test site restrictions related to avoiding activities for 12 
hours prior to clinic visits and 12 hours after test article application that might affect the quantity 
of quality samples collected, impact the signs and symptoms of AD, or remove test articles from 
the treatment sites. Images of both treated sites will be taken at all visits except Screening. Subjects 
will be queried for adverse events during their follow up visits.  
Study Endpoints 
4.2.1 Primary Endpoint 
The hypothesis of this trial related to clinical effect is that 4 weeks of daily dosing with DBI-
001 will improve the signs and symptoms of AD in comparison of sites treated with DBI-001 
DP or Aqueous Gel on the following: 
• 
Change from baseline in ADSI score at days 7 (±2), 14 (±2), 21 (±2), 28 (±2), 35 (±4), and 
42 (±4). 
• 
Change from baseline in individual signs and symptoms of AD (components of ADSI score) 
at days 7 (±2), 14 (±2), 21 (±2), 28 (±2) 35 (±4), and 42 (±2). 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
4.2.2 Secondary Endpoints 
In the S. aureus MITT population, comparison of sites treated with DBI-001 or Aqueous Gel 
on the following microbial metrics: 
• 
Change from baseline in abundance of S. aureus based on molecular diagnostic qPCR and 
CFU counts on samples obtained from treatment sites at days 7, 14, 21, 28, 35, and 42. 
• 
Abundance of DB02473 based on qPCR and CFU counts. 
• 
Changes in the abundance and diversity of the microbiome as determined by 16s and/or 
whole genome sequencing. 
• 
The proportion of subjects with a greater decrease in ADSI for the DBI-001-treated site than 
the Aqueous Gel-treated site. 
• 
Change from baseline in signs and symptoms of local tolerability (pruritus, erythema, 
exudation, excoriation, and lichenification as well as pain, burning, or stinging) for the DBI-
001-treated lesion and the Aqueous Gel-treated lesion. 
INVESTIGATIONAL PRODUCT (IP)  
Investigational Product and Aqueous Gel (Test Articles) 
Test articles 
Doses per 
Subject 
1mL vial contains  DBI-001 Gel with 107-109 CFU / 
mL of DB02473 or Aqueous Gel 
27 doses 
(once daily 
for 4 weeks) 
ELIGIBILTY CRITERIA 
Inclusion Criteria 
Subjects must meet all of the following criteria to be included in the study: 
 
1. Ability to understand, agree to, and sign the study Informed Consent. If the subject is unable 
to provide consent for him/herself, the subject’s legally authorized representative may provide 
written consent. 
 
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 or Female Subjects of any race 12-65 years of age.  
 
4. Physician diagnosed clinically stable AD according to the criteria of Hanifin and Rajka with 
comparable anatomically symmetrical, bilateral target lesions (Hanifin and Rajka 1980). Each 
lesion must have an Atopic Dermatitis Severity Index (ADSI) score of ≥ 6. It will be in the 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
opinion of the Investigator based on subject’s medical history whether the lesions are clinically 
stable. 
 
5. Female subjects of child-bearing potential must use at least one method of birth control that 
results in a low failure rate (i.e., less than 3 % per year) when used consistently and correctly 
such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), 
sexual abstinence or vasectomized partner for the duration of study participation. 
 
6. Technical ability and willingness to self-apply, or LAR to apply, test articles during telemed 
visits with the study staff. 
 
7. Willingness to discontinue use of systemic AD treatments and topical treatments to the target 
areas for the duration of the study unless specifically permitted by the Investigator.  
 
8. Willingness to comply with test site restriction for 12 hours prior to all office visits including 
the Baseline visit and for 12 hours after each treatment application. These treatment site 
restrictions include: 
a. No washing of test sites with any cleansers or soaps. Water passing over the areas 
during showering is acceptable. 
b. No rubbing the test sites with a washcloth, towel, luffas. Pat dry after showering is 
acceptable. 
c. No recreational activities in chlorinated or chemically treated water such as swimming 
pools, hot tubs, and spas. 
d. No tight or form fitting clothing covering the treatment areas. 
e. No sunbathing or use of suntan parlors or tanning beds. 
f. If participating in physical activities resulting in heavy perspiration only pat dry test 
site areas with towel if needed. 
g. Any activity that in the opinion of the investigator might alter the quality of the 
samples collected or risk removal of the test article. 
 
9. Willingness to undergo the following washout periods: 
a. Washout of 2 weeks prior to the Baseline visit for topical treatments used on the two 
treatment target sites, including but not limited to: antibacterial products, anti-
inflammatories (e.g., corticosteroids, tacrolimus, Pimecrolimus). Other than the two 
treatment sites, topical medications may be used before/during the duration of the study. 
Subjects will be provided 1% hydrocortisone for treating non-target areas during the trial. 
 
b. Washout of 4 weeks prior to the Baseline visit for systemic treatments for AD, 
including but not limited to corticosteroids (oral or intramuscular injections), systemic 
immunomodulators or immunosuppressors (e.g., methotrexate, cyclosporine, 
hydroxychloroquine), antibiotics (oral or injected, if required to treat a medical condition 
short duration of oral antibiotics (≤10 days) are permitted after randomization) 
c. Washout of 2 weeks prior to the Baseline visit for bleach baths. 
d. Washout of 2 weeks prior to the Baseline visit for phototherapy. 
 
10. No history of allergy to at least two of the following classes of antibiotics: 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
Cephalosporins, Quinolones, Tetracyclinea, Aminoglycosides Macrolides, Carbapenems and 
Lipopeptides. 
 
11. Willingness to allow digital photos of treatment areas to be taken and stored. 
Exclusion Criteria 
The following are the exclusion criteria that will exclude subjects from enrolling into the trial: 
 
1. Women who are pregnant, planning a pregnancy, breastfeeding or have a positive 
pregnancy test at screening. 
 
2. Any dermatological conditions that could interfere with clinical evaluations or any 
disease state or physical condition which might expose the subject to an unacceptable risk 
by study participation. 
 
3. Any underlying disease(s) or other dermatological conditions that require the use of 
exclusionary topical or systemic therapy.  
 
4. Spontaneously improving or rapidly deteriorating dermatitis anywhere on the body. 
 
5. Netherton’s syndrome or other genetic dermatoses that result in defective epidermal 
barrier function. 
 
6. Treatment of any type of cancer within the last 6 months other than cutaneous basal cell 
carcinoma. 
 
7. History of any significant internal disease (which contraindicates use of live microbiome 
e.g. leukemia, liver failure, cardiovascular disease). 
 
8. Subjects who are known to be allergic to any of the test product(s) or any components in 
the test product(s) or have a history of hypersensitivity or allergic reactions to any of the 
study preparations as described in the Investigator’s Brochure. 
 
9. AIDS or AIDS related complex by medical history. 
 
10. Known or suspected immune suppressive medications or diseases or any condition that in 
the opinion of the investigator would increase the subject’s susceptibility to opportunistic 
infections. 
 
11. Treatment with systemic immune modulating or anti-inflammatory biologics agents 
within 16 weeks of Baseline Visit. 
 
12. Poorly controlled diabetes mellitus Type I or II by medical history. 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
13. Peripheral vascular disease based on medical history. 
 
14. Any subject not able to meet the study attendance and telemed visit requirements. 
 
15. Participants with a history of psychiatric disease or history of alcohol or drug abuse that 
would interfere with the ability to comply with the study protocol. 
 
16. 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. 
 Recruitment and Retention 
Subjects will be recruited from the Investigator’s clinical dermatology practice. Subjects may also 
be recruited through the use of recruitment material(s) approved by the study IRB or Ethics 
Committee. 
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 documented 
accordingly.  Subjects may be replaced at the discretion of the Investigator and/or 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 
Study discontinuation is at the discretion of the Sponsor or the Investigator in any of, but not 
limited to, the following events: 
• 
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. 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
 
6.4.3 Stopping Rules 
The sponsor (Medical Director/Chief Medical Officer) will halt the study for a review of the safety 
data if there are safety concerns noted for any reason and if one or more subjects experience two 
AE’s assessed as a Grade 3 (severe) or higher, of the same type that is considered possibly, 
probably or definitely related to the IP. 
Study Visits 
The study will be conducted with a Screening visit, Day 1 / Baseline visit, Study Day visits 7, 14, 
21, 28 and two follow-up visits on Days 35 and 42.   
 
If reported violations of treatment site restrictions occurred prior to the visit at Screening, Day 1 / 
Baseline, Day 7, 14 or 21, details of the violation should be recorded in the CRF and the 
evaluations and sampling completed as scheduled. 
If reported violations of treatment site restrictions occurred less than 24 hours prior to the visit at 
Day 28, 35, or 42, details of the violation should be recorded in the CRF and evaluations can be 
completed, but an additional visit 24-48 hours after the violation should be scheduled for sample 
collections. However, if reported violations of treatment site restrictions occurred more than 24 
hours prior to the visit at Day 28, 35, or 42, details of the violation should be recorded in the 
CRF and the evaluations and sampling completed as scheduled. 
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 evaluations.  
 
(-14 Day to Day 0) Screening visit: 
1. 
Informed consent. 
2. 
Record demographics. 
3. 
Review of Inclusion/Exclusion Criteria. 
4. 
Women of childbearing potential will be tested for pregnancy with a urine pregnancy 
test. 
5. 
Medical history. 
6. 
Concomitant medication. 
7. 
Record adverse event, if any. 
8. 
Clinical assessment of signs and symptoms of AD Calculate ADSI score of both 
potential treatment sites.  
9. 
Schedule baseline visit 
 
Screening and Day 1 / Baseline visit can be on the same day. 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
 
Continuous monitoring of concomitant medications, therapies, and AEs throughout the study 
period will begin at the Screening visit. 
 
6.5.2 All Other Visits 
Study visit assessments and sample collections will be conducted as presented in Tables 2 and 3. 
 
The Screening and Day 1/Baseline visit can be combined for subjects meeting all eligibility 
requirements and only if all Screening and Day 1/Baseline tests and tasks can be completed on the 
same day. 
 
Day 1/Baseline visit: 
1. Confirm compliance with treatment site restrictions. 
2. Record any changes in concomitant medications. 
3. Record adverse event, if any. 
4. Blinded evaluating investigator complete clinical assessment of severity of signs and 
symptoms of AD prior to application of test article. 
5. Calculate ADSI score of both potential treatment sites if the Screening visit was on an earlier 
date.  At Baseline, if ADSI eligibility criterion is no longer met, the subject is to be withdrawn 
from the study prior to sample collection and test article application. 
6. Digital images of both treatment sites. 
7. Collect PBS swabs from both treatment sites. 
8. Collect samples for cytokine profiling from both treatment sites.  
9. Unblinded treating investigator, or designee, to train subjects and/or LAR  on method for self-
 or LAR to apply with a training vial. 
10. Unblinded treating investigator, or designee, apply test articles after all evaluations and 
sampling have been completed. 
11. Blinded evaluating investigator complete clinical assessment of local tolerability (severity 
pain, burning, or stinging in addition to pruritus, erythema, exudation, excoriation, and 
lichenification) 30-minutes after application of test articles to both treatment sites. 
12. Review treatment site restrictions. 
13. Review procedures for telemed visits. 
14. Dispense 1% hydrocortisone ointment as needed. 
15. Schedule appointment for Day 7 clinic visit and telemed visits.  
 
Detailed instructions for sample collection, storage, and shipping are in the Collection Sampling, 
Storage, Shipping Procedure (CSSSP) provided separately. If violations of treatment site 
restrictions prior to the visit are reported details of the violation should be recorded in the CRF and 
the visit should be completed including evaluations and sampling. 
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PROPRIETARY AND CONFIDENTIAL 
 
Day 7 (±2) 
 
1. Confirm compliance with treatment site restrictions. 
2. Record any changes in concomitant medications. 
3. Record adverse event, if any. 
4. Blinded evaluating investigator complete clinical assessment of severity of signs and 
symptoms of AD. 
5. Blinded evaluating investigator complete clinical assessment of local tolerability (severity 
pain, burning, or stinging in addition to pruritus, erythema, exudation, excoriation, and 
lichenification). 
6. Calculate ADSI score of both potential treatment sites. 
7. Digital images of both treatment sites. 
8. Collect PBS swabs from both treatment sites. 
9. Unblinded treating investigator, or designee, apply test articles after all evaluations and 
sampling have been completed. 
10. Collect used and unused returned test articles. 
11. Dispense test articles for home treatment. 
12. Review treatment site restrictions. 
13. Dispense 1% hydrocortisone ointment as needed. 
14. Schedule appointment for Day 14 clinic visit and telemed visits. 
 
Detailed instructions for sample collection, storage, and shipping are in CSSSP provided 
separately. If violations of treatment site restrictions prior to the visit is reported details of the 
violation should be recorded in the CRF and the visit should be completed including evaluations 
and sampling. 
 
Day 14 (±2) 
 
1. Women of childbearing potential will be tested for pregnancy with a urine pregnancy test. 
2. Confirm compliance with treatment site restrictions. 
3. Record any changes in concomitant medications. 
4. Record adverse event, if any. 
5. Blinded evaluating investigator complete clinical assessment of severity of signs and 
symptoms of AD. 
6. Blinded evaluating investigator complete clinical assessment of local tolerability (severity 
pain, burning, or stinging in addition to pruritus, erythema, exudation, excoriation, and 
lichenification). 
7. Calculate ADSI score of both potential treatment sites. 
8. Digital images of both treatment sites. 
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PROPRIETARY AND CONFIDENTIAL 
9. Collect PBS swabs from both treatment sites. 
10. Unblinded treating investigator, or designee, apply test articles after all evaluations and 
sampling have been completed. 
11. Collect used and unused returned test articles. 
12. Dispense test articles for home treatment. 
13. Review treatment site restrictions. 
14. Dispense 1% hydrocortisone ointment as needed. 
15. Schedule appointment for Day 21 clinic visit and telemede visits. 
 
Detailed instructions for sample collection, storage, and shipping are in the CSSSP provided 
separately. If violations of treatment site restrictions prior to the visit is reported details of the 
violation should be recorded in the CRF and the visit should be completed including evaluations 
and sampling 
 
Day 21 (±2) 
 
1. Confirm compliance with treatment site restrictions. 
2. Record any changes in concomitant medications. 
3. Record adverse event, if any. 
4. Blinded evaluating investigator complete clinical assessment of severity of signs and 
symptoms of AD. 
5. Blinded evaluating investigator complete clinical assessment of local tolerability (severity 
pain, burning, or stinging in addition to pruritus, erythema, exudation, excoriation, and 
lichenification). 
6. Calculate ADSI score of both potential treatment sites. 
7. Digital images of both treatment sites. 
8. Collect PBS swabs from both treatment sites. 
9. Unblinded treating investigator, or designee, apply test articles after all evaluations and 
sampling have been completed. 
10. Collect used and unused returned test articles. 
11. Dispense test articles for home treatment. 
12. Review treatment site restrictions. 
13. Dispense 1% hydrocortisone ointment as needed. 
14. Schedule appointment for Day 21 clinic visit and telemed visits. 
Detailed instructions for sample collection, storage, and shipping are in the CSSSP provided 
separately. If violations of treatment site restrictions prior to the visit is reported details of the 
violation should be recorded in the CRF and the visit should be completed including evaluations 
and sampling. 
 
Day 28 (±2) Follow up visit (no treatment) 
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PROPRIETARY AND CONFIDENTIAL 
1. Confirm compliance with treatment site restrictions 
2. Record any changes in concomitant medications. 
3. Record adverse event, if any. 
4. Blinded evaluating investigator complete clinical assessment of severity of signs and 
symptoms of AD. 
5. Blinded evaluating investigator complete clinical assessment of local tolerability (severity 
pain, burning, or stinging in addition to pruritus, erythema, exudation,  excoriation, and 
lichenification). 
6. Calculate ADSI score of both potential treatment sites. 
7. Digital images of both treatment sites 
8. Collect PBS swabs from both treatment sites 
9. Collect samples for cytokine profiling from both treatment sites  
10. Review treatment site restrictions with subject 
11. Dispense 1% hydrocortisone ointment as needed 
12. Schedule appointment for Day 35 clinic visit  
 
Detailed instructions for sample collection, storage, and shipping are in the CSSSP provided 
separately. 
If reported violations of treatment site restrictions occurred more than 24 hours prior to the Day 
28 visit, details of the violation should be recorded in the CRF and the evaluations and sampling 
completed as scheduled. 
If reported violations of treatment site restrictions occurred less than 24 hours prior to the Day 28 
visit, details of the violation should be recorded in the CRF the evaluations can be completed, but 
an additional visit 24-48 hours after the violation should be scheduled for sample collections. 
Day 35 (±4) Follow up visits (no treatment) 
 
1. Confirm compliance with treatment site restrictions. 
2. Record any changes in concomitant medications. 
3. Record adverse event, if any. 
4. Blinded evaluating investigator complete clinical assessment of severity of signs and 
symptoms of AD. 
5. Blinded evaluating investigator complete clinical assessment of local tolerability (severity 
pain, burning, or stinging in addition to pruritus, erythema, exudation, excoriation, and 
lichenification). 
6. Calculate ADSI score of both potential treatment sites. 
7. Digital images of both treatment sites. 
8. Collect PBS swabs from both treatment sites. 
9. Review treatment site restrictions. 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
10. Dispense 1% hydrocortisone ointment as needed. 
11. Schedule appointment for Day 42. 
Detailed instructions for sample collection, storage, and shipping are in the CSSSP provided 
separately.  
 
If reported violations of treatment site restrictions occurred more than 24 hours prior to the Day 
35 visit, details of the violation should be recorded in the CRF and the evaluations and sampling 
completed as scheduled. 
If reported violations of treatment site restrictions occurred less than 24 hours prior to the Day 35 
visit, details of the violation should be recorded in the CRF the evaluations can be completed, but 
an additional visit 24-48 hours after the violation should be scheduled for sample collections. 
Day 42 (±4) Follow up visits (no treatment) 
 
1. Women of childbearing potential will be tested for pregnancy with a urine pregnancy test. 
2. Confirm compliance with treatment site restrictions 
3. Record any changes in concomitant medications. 
4. Record adverse event, if any. 
5. Blinded evaluating investigator complete clinical assessment of severity of signs and 
symptoms of AD. 
6. Blinded evaluating investigator complete clinical assessment of local tolerability (severity 
pain, burning, or stinging in additional to in addition to pruritus, erythema, exudation, 
excoriation, and lichenification). 
7. Calculate ADSI score of both potential treatment sites. 
8. Digital images of both treatment sites 
9. Collect PBS swabs from both treatment sites 
10. Dispense 1% hydrocortisone ointment as needed 
 
Detailed instructions for sample collection, storage, and shipping are in the CSSSP provided 
separately.  
 
If reported violations of treatment site restrictions reported occurred more than 24 hours prior to 
the Day 42 visit, details of the violation should be recorded in the CRF and the evaluations and 
sampling completed as scheduled. 
If reported violations of treatment site restrictions occurred less than 24 hours prior to the Day 42 
visit, details of the violation should be recorded in the CRF the evaluations can be completed, but 
an additional visit 24-48 hours after the violation should be scheduled for sample collections. 
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PROPRIETARY AND CONFIDENTIAL 
Study Specific Procedures 
Clinical Evaluations: 
All primary endpoint assessments must be done by an observing evaluating investigator who is a 
board-certified dermatologist. Investigators who are not board-certified dermatologists may 
perform the role of an observing, evaluating investigator at the Sponsor’s discretion.  
 
6.6.1 Grading of signs and symptoms of AD using ADSI  
Both targeted treatment areas will be evaluated using the ADSI. The ADSI score represents the 
sum of the individual severity scores on none, mild, moderate, or severe for the following 
component signs and symptoms: erythema, pruritus, exudation, excoriation and lichenification.  
The investigators will only be required to calculate the ADSI at the Screening and Baseline visits 
to confirm that the subjects meet the inclusion criteria for disease severity. The ADSI for 
subsequent visits will be calculated during data analysis. The same observer-blinded investigator 
should perform the ADSI grading for each subject for the duration of a subject’s participation in 
the study. 
 
The same signs and symptoms of AD are also commonly use to evaluate application site -
reactions to topical product and serves a secondary role in characterizing tolerability. The 
sponsor will consider improvement in the ADSI and the individual signs and symptoms of AD 
an indicator of either a favorable therapeutic effect or the demonstration of the natural variation 
of AD over time. If the signs and symptoms increase in severity, the sponsor will consider this an 
indication of an application site reaction and/or the natural variation in AD over time. To further 
characterize local tolerability, subject self-reporting of pain, burning, or stinging will also be 
recorded. Each component is measured using the following scale: 
 
Erythema score: (redness presents specifically in the target lesion) 
 0=none           No redness  
             1=mild           Mildly detectable erythema; pink 
             2=moderate   Dull red; clearly distinguishable 
             3=severe        Deep, dark red; marked and extensive 
 
Exudation score: (oozing or crusting of the target lesion) 
0=none          No oozing or crusting  
            1=mild          Minor or faint signs of oozing 
2=moderate   Definite oozing or crusting present 
3=severe        Marked and extensive oozing or crusting present  
 
Excoriation score: (evidence of scratching in the target lesion) 
 0=none         No evidence of excoriation 
 1=mild          Slight excoriation present 
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PROPRIETARY AND CONFIDENTIAL 
 2=moderate   Definite excoriation present 
 3=severe        Marked, deep, or extensive excoriation present 
 
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  
 
Lichenification score: (epidermal thickening of the target lesion) 
 0=none            No epidermal thickening 
 1=mild            Minor epidermal thickening 
 2=moderate    Definite epidermal thickening; accentuated skin lines 
             3=severe         Marked epidermal thickening; deeply accentuated skin lines 
 
To calculate the ADSI score, the component scores are added together. 
 
6.6.2 Local Tolerability  
Tolerability will be evaluated based on calculating the scores for pruritus, erythema, exudation, 
excoriation, lichenification and the additional symptoms of pain, burning, or stinging using the 
following scale: 
 
Pain, Burning, or Stinging: 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, or stinging 
1          Mild            
Slight pain, burning or stinging sensation; not really bothersome 
2          Moderate     
Definite pain, burning or stinging that is somewhat  
bothersome 
3          Severe         
Significant pain, burning, or stinging sensation that causes definite  
discomfort and may interrupt daily activities and/or sleep. 
6.6.3 Sample Collection 
Samples for microbiologic and cytokine testing will be obtained separately from both treatment 
targeted sites as detailed in Table 2 below. Details of sample collection, storge, and shipment can 
be found in the CSSSP. 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
Table 2. Microbiological and Cytokine profiling Samples. 
 
If the atopic dermatitis has cleared completely in a treatment site, the investigator is to use 
clinical judgment, anatomical landmarks and previously captured digital images to identify the 
specific location to be sampled. 
Test Article Administration  
All subjects will have approximately 27 applications of the assigned test articles applied to each 
treatment site by unblinded study personnel at the Day 1/Baseline, Day 7, Day 14 and Day 21 
visits. Doses between visits will be applied by the subjects, or LAR, under the supervision of an 
unblinded treating investigator, or designee, during telemed visits on weekdays and unsupervised 
on weekends. Details of test article preparation are in the Pharmacy Instruction Manual, provided 
Visit 
Sample 
Test 
Screening 
None 
  
Day 1 (Baseline -
Prior to 
Application) 
1 Swab and 12 tape sample for cytokine profiling 
from each treatment site 
qPCR 
Bacterial Culture 
S. aureus CFU 
 
Cytokine Profile 
Day 7 
1 Swab from each treatment site  
qPCR 
Bacterial Culture 
S. aureus CFU 
 
Day 14 
1 Swab from each treatment site 
qPCR 
Bacterial Culture 
S. aureus CFU 
 
Day 21 
1 Swab from each treatment site 
qPCR 
Bacterial Culture 
S. aureus CFU 
 
Day 28 
1 Swab and 12 tape sample for cytokine profiling 
from each treatment site 
                 qPCR 
Bacterial Culture 
S. aureus CFU 
 
Cytokine Profile 
Day 35 
1 Swab from each treatment site  
qPCR 
Bacterial Culture 
S. aureus CFU 
 
Day 42 
1 Swab from each treatment site  
qPCR 
Bacterial Culture 
S. aureus CFU 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
separately. Approximately 0.1 ml of assigned test article will be applied to each treatment site 
(each site is approximately 100 cm2). The product is to be air dried.  
 
If technical or other logistical issues prevent a telemed connection (i.e., a weekday telemed is 
missed for any reason) the subject is to apply test articles unsupervised.  
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. Subjects will be supplied with 1% Hydrocortisone 
Ointment to treat areas of A remote from the designated treatment sites. 
Randomization 
Each enrolled subject will be randomized to a test article kit number containing two different 
vials of test articles for each scheduled application. Each kit will contain vials labelled with 
“Right” or “Left”, indicating the treatment side to apply onto. Treatment compliance will be 
monitored by recording all missed doses in source documentation and the CRF. 
DATA ANALYSIS AND STATISTICAL CONSIDERATION. 
 General Statistical Considerations 
All statistical processing will be performed using Statistical Analysis System (SAS®) unless 
otherwise stated. No interim analyses are planned. Except where noted, all statistical tests will be 
two-sided and will be performed at the 0.05 level of significance. P-values will be provided 
primarily for exploratory purposes. 
 
Descriptive statistics will be used to provide an overview of the efficacy and safety results. For 
categorical parameters, the number and percentage of subjects in each category will be presented. 
For continuous parameters, descriptive statistics will include the number of subjects, mean, and 
standard deviation, median, minimum, and maximum. Appropriate inferential statistics will be 
used for the primary and secondary efficacy variables in an exploratory manner. 
 
Linear interpolation of efficacy variables will be performed using observed data that precedes and 
follows the off-schedule visit, if present. The last observation will be carried forward if all the data 
subsequent to the off-schedule value is missing. 
 
No adjustments will be made for multiplicity. 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
The number of subjects in each analysis set will be summarized. Reasons for study withdrawal 
will be summarized using frequencies and percentages by treatment group. 
 
Reported AEs, medical history terms and prior and concomitant procedures and therapies will be 
classified on the basis of the f Medical Dictionary for Regulatory Activities (MedDRA) 
terminology.  Prior and concomitant medications will be classified on the basis of the World 
Health Organization Drug Dictionary (WHO-DDE) terminology. 
 
A statistical analysis plan (SAP), describing all statistical analyses will be provided as a separate 
document. The SAP will be finalized prior to unblinding of the study treatments. 
Analysis of Efficacy Data for Objectives 
7.2.1 Primary Efficacy:  
The primary analysis will compare the differences from baseline in ADSI score between DBI-
001 and Aqueous Gel will be done using a two-sided Wilcoxon sign rank test at each of Days 
7, 14, 21, 28 ,35 and 42.  
 
The proportion of subjects with a greater decrease in ADSI for the DBI-001-treated lesion than 
the Aqueous Gel-treated lesion will be summarized descriptively for Days 7, 14, 21, 28, 35, 
and 42. 
 
Comparison of differences at Day 28 between DBI-001 and Aqueous Gel of abundance of 
DB02473 on lesioned skin will be done using a two-sided Wilcoxon sign rank test.  
 
Comparison of differences at Day 28 between DBI-001 and Aqueous Gel of abundance and 
diversity of the microbiome based on DNA sequencing will be done using a two-sided 
Wilcoxon sign rank test. 
 
Comparisons at Days 7, 14, 21, 35, and 42 will also be done. Additionally, a repeated 
measures model will be used to compare DBI-001 to Aqueous Gel for the secondary 
endpoints. P-values will be provided for descriptive purposes. 
 
7.2.2 Secondary Efficacy: 
The secondary analysis of the S. aureus MITT population will compare the differences at Day 
28 between DBI-001 DP and Aqueous Gel in abundance of S. aureus based on qPCR using a 2-
sided Wilcoxon sign rank test, alpha = 0.05, with a null hypothesis of median difference equal 
to zero.  
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
Comparisons at Days 7, 14, 21, and 35 will also be done. Additionally, a repeated measures 
model will be used to compare DBI-001 DP to Aqueous Gel for the secondary endpoints. P-
values will be provided for descriptive purposes. 
 
7.2.3 Exploratory Efficacy: 
Comparison in changes in the overall microbiome as defined by whole genome sequencing of 
samples obtained prior to, during, and after treatment. 
 
Comparison of change from baseline in individual signs and symptoms of AD (components of 
ADSI score) between DBI-001 DP and Aqueous Gel will be done using a two-sided sign test at 
each of Days 7, 14, 21, 28, 35, and 42. 
 
Additionally, a repeated measures model will be used to compare DBI-001 DP to Aqueous Gel 
for the above exploratory endpoints. 
7.3 Analysis of Safety Data for Objectives 
7.3.1 Local Tolerability 
Signs and symptoms of local tolerability pruritus, erythema, exudation, excoriation,  
lichenification as well as pain, burning, or stinging) will be summarized with changes from 
baseline. 
 
7.3.2 Adverse Events 
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, seriousness, action taken 
regarding the investigational product, corrective treatment, outcome, and Investigator’s 
assessment of causality. All reported treatment-emergent AEs (TEAEs), defined as any AE with 
an onset on or after the date of first investigational product application, will be summarized by 
treatment group, the number of subjects reporting TEAEs, system organ class, preferred term, 
severity, and relationship to investigational product. When summarizing TEAEs by severity or 
relationship to investigational product, each subject will be counted only once within a system 
organ class or a preferred term using the event with the greatest severity or causality, respectively, 
within each category. All reported serious adverse events (SAEs) will be summarized by treatment 
group, the number of subjects reporting SAEs, system organ class, preferred term, severity, and 
relationship to investigational product. 
 
All information pertaining to AEs noted during the study will be listed by subject and will include 
a verbatim description of the event as reported by the Investigator, as well as the preferred term, 
system organ class, start date, stop date (if stopped), seriousness, severity, action taken regarding 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
the investigational product, corrective treatment, outcome and relationship to the investigational 
product. In addition, a listing of subjects who prematurely discontinue from the study due to AEs 
will be provided as well as a listing of subjects who reported an SAE. 
7.4 Analysis Populations 
All subjects who are randomized and dispensed investigational product will be included in the 
Intent-to-Treat analysis set. All subjects who are randomized, receive at least one (1) confirmed 
dose of investigational product, and have at least one (1) post-baseline safety assessment will be 
included in the Safety analysis set.  
7.5 Sample Size Determination 
Sample size is based on clinical judgement and deemed adequate to successfully demonstrate 
these goals. 
4. ASSESSMENT OF SAFETY 
8.1 Safety Evaluations and Criteria 
As detailed in sections 5.6.1 and 5.6.2, local tolerability will be evaluated by recording the severity 
of the signs of AD as well as subjective symptoms of pain, burning, or stinging on treated areas 
involved with AD. In addition, adverse events will be documented. 
8.2 Adverse Event 
An AE refers to any untoward medical occurrence in a subject administered a pharmaceutical 
product, whether or not considered investigational product related. 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 investigational product, whether or not it is considered 
to be investigational product related.  This includes any newly occurring event or previous 
condition that has increased in severity or frequency since the administration of investigational 
product (treatment-emergent). 
8.3 Serious Adverse Event 
A serious adverse event (or adverse reaction, or suspected adverse reaction) refers to any AE, 
occurring at any dose level and regardless of causality that: 
• 
Results in death. 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
• 
Is life-threatening:  Life-threatening means that the subject was at immediate risk of death 
from the event 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). 
• 
Results in inpatient hospitalization or prolongation of an existing hospitalization.  
• 
Results in persistent or significant incapacity, or disability, or substantial disruption of the 
ability to perform normal life functions. 
• 
Is a congenital anomaly or birth defect. 
• 
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 treatment 
in an emergency room, a physician’s office or clinic, 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 an SAE. 
 
8.4 Unexpected Adverse Event 
An AE (or a suspected adverse reaction) is deemed unexpected if itis not reported in the 
Investigator’s Brochure (IB), is not listed at the specificity or severity that has been observed or is 
not consistent with the risk information described in the general investigational plan or elsewhere 
in the current IND studies. 
8.5 Relationship of Adverse Events to Investigational Product 
The following classifications should be used when evaluating the relationship of AEs and SAEs 
to the investigational product. 
1. Unrelated: No relationship between the experience and the administration of investigational 
product; related to other etiologies such as concomitant medications or subject’s clinical 
state. 
2. Probably not related: The current state of knowledge indicates that a relationship is 
unlikely.   
3. Possibly related: A reaction that follows a plausible temporal sequence from administration 
of the investigational product and follows a known response pattern to the suspected 
investigational product. The reaction might have been produced by the subject’s clinical state 
or other modes of therapy administered to the subject. 
4. Probably related: A reaction that follows a plausible temporal sequence from administration 
of the investigational product and follows a known response pattern to the suspected 
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PROPRIETARY AND CONFIDENTIAL 
investigational 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 related: A reaction that follows a plausible temporal sequence from 
administration of the investigational product and follows a known response pattern to the 
suspected investigational product and can be confirmed with a positive re-challenge test or 
supporting laboratory data. 
8.6. Intensity: Classification of Intensity of Adverse Event. 
The following classifications should be used when evaluating the intensity of AE’s and SAE’s: 
 
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 
5. 
Death 
PROCEDURES FOR ADVERSE EVENT RECORDING AND REPORTING 
Emergency Sponsor Contact 
In the event of a medical emergency (i.e., an event that requires immediate attention regarding the 
treatment of a subject, operation of the clinical study, and/or the use of investigational drug), 
investigational site personnel must immediately contact the Medical Monitor. 
Medical Monitor Contact 
Name: 
Donald Chalfin, MD, MS, MPH (primary) 
Telephone: 
516-448-0047  
Email: 
donald@dermbiont.com 
 
Name: 
Emma Taylor, MD (secondary) 
Telephone: 
626-260-1230  
Email: 
emma@dermbiont.com 
Other Required Safety Assessments 
A clinically significant worsening from Baseline of any abnormal study assessment should be 
considered an AE and recorded accordingly.  If possible, a diagnosis for the clinically significant 
study assessment should be provided by the Investigator (e.g., Urinary tract infection or anemia). 
In the absence of a diagnosis, the abnormal study assessment itself should be listed as the AE (e.g., 
bacteria in urine or decreased hemoglobin).  
 
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PROPRIETARY AND CONFIDENTIAL 
An abnormal study assessment is considered clinically significant if the subject has one or more 
of the following related to the abnormal study assessment: 
1. 
Concomitant clinical signs or symptoms. 
2. 
Further diagnostic testing or medical/surgical intervention. 
3. 
Discontinued from the study. 
 
Repeat testing to determine whether the result is abnormal, in the absence of any of the above 
criteria, does not necessarily meet clinically significant criteria. The determination of whether the 
study assessment results are clinically significant must be made by the Investigator. 
SPECIAL REQUIREMENTS AND PROCEDURES 
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, CRFs, source documents 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. 
Audits and Inspections 
The Investigators and clinical sites will permit study related monitoring, audits, IRB/IEC review, 
and regulatory inspections as requested by the regulatory authorities, 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. 
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 
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PROPRIETARY AND CONFIDENTIAL 
outlined in these documents along with the identification that a signed informed consent must be 
obtained prior to a subject participation in the study. 
 Confidentiality 
To maintain subject privacy, all eCRFs, study samples, investigational product 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. 
 
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. 
 Subject Rights 
Study subjects can withdraw their consent to have their clinical samples stored even after the 
sample has been shipped to the sponsor laboratory. A study subject should contact the Investigator 
or the Investigator’s designee and ask for his/her sample to be withdrawn from the storage 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. 
 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. 
 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
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. 
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.  
 
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 product administrations; recording the subject’s data on the source documents and 
CRFs; documenting the presence or absence of AEs following sample collection and 
investigational product applications and following the reporting requirements of any SAEs to the 
Sponsor and IRB/IEC.  
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. 
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.   
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
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. 
 
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. 
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. 
DATA HANDLING AND RETENTION OF RECORDS 
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 
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. 
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 
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Protocol # DBI-207, V# 05- 16 December 2021 
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PROPRIETARY AND CONFIDENTIAL 
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. 
 
 
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