Clinical trial NCT03386032
Conditions: Atopic Dermatitis Eczema
Sponsor: Procter and Gamble
Start date: 2017-11-27; Completion date: 2018-08-18
Enrollment: 65 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a study to investigate the clinical effectiveness of the Sponsor's experimental cream treatment on eczema as measured by visual grading of SCORAD (scoring of atopic dermatitis).

Detailed description:
This will be a 9-week, randomized, double blind, parallel comparison study consisting of a 1-week washout phase followed by an 8-week treatment phase. This study will be executed by one clinical research company utilizing two test sites and up to 62 subjects with moderate or severe atopic dermatitis, ages 12-65, will be enrolled. Subjects that are enrolled will be placed on one of three products (e.g. Sponsor's Experimental Cream Treatment, a basic moisturizer, or a positive control - Desonide) and will be required to use the assigned product twice a day for the duration of the 8-week treatment phase.

Arms: arm 1: Investigational Over the Counter (OTC) Cream will be applied topically, twice daily, for 8 weeks, once in the morning and once in the evening, to atopic dermatitis lesions and whole body as moisturizer. arm 2: Placebo Cream will be applied topically, twice daily, for 8 weeks, once in the morning and once in the evening, to atopic dermatitis lesions and whole body as body moisturizer. arm 3: Rx Steroid applied topically, twice daily, once in the morning and once in the evening, for 8 weeks to all atopic dermatitis lesions.

Placebo Cream applied topically, twice daily, for 8 weeks, once in the morning and once in the evening, to whole body as body moisturizer, except atopic dermatitis lesions.
Interventions: intervention 1: Investigational OTC Cream intervention 2: 0.05% Desonide intervention 3: Placebo Cream
Intervention descriptions: intervention 1: Investigational Over the Counter (OTC) Cream applied topically, twice daily, for 8 weeks, once in the morning and once in the evening, to atopic dermatitis lesions and whole body as moisturizer. intervention 2: Rx Steroid applied topically, twice daily, once in the morning and once in the evening, for 8 weeks to all atopic dermatitis lesions.

Placebo Cream applied topically, twice daily, for 8 weeks, once in the morning and once in the evening, to whole body as body moisturizer, except atopic dermatitis lesions. intervention 3: Placebo Cream applied topically, twice daily, for 8 weeks, once in the morning and once in the evening, to atopic dermatitis lesions and whole body as body moisturizer.

Protocol documents:
Prot_002.pdf: 
 
 
 
 
 
 
 
 
 
 
 
 
8-Week Atopic Dermatitis (AD) Treatment Study 
NCT03386032 
April 27, 2018 
 
 
 


Page 1 of 13 
 
CLINICAL STUDY PROTOCOL 
 
Title:   
8-Week Atopic Dermatitis (AD) Treatment Study 
Study Number: 
CSD2017168  
Date Issued: 
April 27, 2018 
Expected Start Date:   
December 6 ,2017 
Expected Completion Date:  
July 15, 2018  
Test Facility: 
Wake Research Associates, LLC      WR-ClinSearch, LLC 
 
3100 Duraleigh Rd., Suite #304             6035 Shallowford Road, Suite #109                
 
Raleigh, NC  27612                                 Chattanooga, TN  37421 
 
Phone: 919-781-2514            
Sponsor Facility: Procter and Gamble Company 
                              11510 Reed Hartman Highway 
                              Cincinnati, OH  45241      
                                       
Sponsor and Investigator Concurrence 
I have reviewed the attached protocol and its associated documents.  This clinical study will be conducted in 
compliance with Federal, state, and local government regulations, guidelines, and standards applicable to 
such studies including, but not limited to, those relating to ICH E6 and Good Clinical Practices Guidelines, 
including Informed Consent.  The Investigator agrees to abide by the terms of this protocol. 
 
Sponsor: 
Work Phone: 
Alternate Phone: 
 
 
 
 
 
Debora Whittenbarger, B.S.N., R.N. 
date 
513-626-1620 
513-368-4551 
 
Clinical Trial Manager 
                           
e-mail: whittenbarger.dj@pg.com 
 
 
 
 
 
 
          Dawn Yeomans, PhD 
date 
 
513-498-4518  
      315-982-4636 
 
Clinical Scientist 
 
 
e-mail: yeomans.dj@pg.com 
 
 
 
 
 
Laurie Moulton, MS 
                         date 
513-626-0215 
 
Statistician 
 
 
 
e-mail: moulton.lt@pg.com 
 
 
 
Suska Bentz, AS 
date 
513-626-3912 
513-293-3942 
 
Data Manager 
 
 
 
e-mail: bentz.si@pg.com 
 
 
 
 
 
 
Michael Marmor B.S.                                       date 
513- 626-0140  
        513-382-3348 
 
Imaging Coordinator 
 
 
e-mail: marmor.mj@pg.com 
 
Test Site Investigators 
 
 
 
Adnan Nasir, MD, PhD 
 
date  
919-781-2514 
 
Principal Investigator, Raleigh Site 
 
e-mail: anasir@wakeresearch.com 
 
             423-698-4584 
Dr. Richard Krause, MD 
Principal Investigator Chattanooga, TN 
 
e-mail: rkrause@clinsearch.com 
 
 
 
 


Page 2 of 13 
 
 
 
 
 
 
TABLE OF CONTENTS 
I. 
Objective...................................................................................................................................................................................... 2 
II. Background................................................................................................................................................................................ 3 
A. 
Study Design ....................................................................................................................................................................... 3 
B. 
Study Schedule (listed in procedure order) ............................................................................................................... 5 
III. 
Study Population ................................................................................................................................................................. 6 
C. 
Packaging, Labeling, and Shipping of Test Products............................................................................................. 7 
VI. 
Subject Accountability ...................................................................................................................................................... 8 
A. 
Subject Identification......................................................................................................................................................... 8 
B. 
Subject Early Withdrawal ................................................................................................................................................ 8 
C. 
Adverse Events .................................................................................................................................................................. 8 
D. 
Illness and Medication Reporting.................................................................................................................................. 8 
VIII.   Other Study Documentation ............................................................................................................................................ 9 
A.        Protocol Amendments .................................................................................................................................................... 9 
B.        Protocol Deviations.......................................................................................................................................................... 9 
C.        Study Monitoring .............................................................................................................................................................. 9 
D.       Additional Data................................................................................................................................................................... 9 
X.    Investigator’s Responsibilities ....................................................................................................................................... 10 
A.         Informed Consent / Assent ........................................................................................................................................ 10 
B.        Final Investigator’s Report........................................................................................................................................... 10 
D. 
Record Retention ............................................................................................................................................................. 11 
E. 
Confidentiality.................................................................................................................................................................... 11 
F. 
IRB Review and Approval ............................................................................................................................................. 11 
XI.   Attachments ............................................................................................................................................................................ 11 
A.    Appendices ........................................................................................................................................................................... 11 
B.   Data Collection Forms (DCFs) ......................................................................................................................................... 12 
C.  Safety Letter............................................................................................................................................................................ 13 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I. 
Objective  
The primary objective of this study is to demonstrate the clinical efficacy of the Sponsor’s experimental eczema 
cream treatment containing formula relative to a basic moisturizer in condition improvement as measured by 


Page 3 of 13 
 
SCORAD (scoring of atopic dermatitis).  The secondary objective is to demonstrate the clinical efficacy of the 
Sponsor’s experimental eczema cream treatment containing a formula relative to a basic moisturizer in condition 
improvement as measured by PGA (physician’s global assessment), EASI (eczema area and severity index), and 
individual lesion assessment by the extent and severity components of SCORAD.  The tertiary objective is to 
demonstrate the clinical efficacy of the Sponsor’s experimental eczema cream treatment containing formula relative 
to a basic moisturizer in condition improvement as measured by Qualify of Life (QoL) and self-assessment 
questionnaires.  The quaternary objective is to understand skin health profiles as measured by biomarker analysis 
from tape strip samples.  
II. 
Background 
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by disruption of epidermal 
barrier function that results in intense pruritus, sleep disturbances, and subacute and chronic eczematous 
lesions.  AD is the most common cause of chronic inflammatory skin disease and is a major cause of 
morbidity and suffering, affecting up to 30% of children, and increasing in prevalence throughout the world. 
It is estimated that the direct cost of AD in the US alone may be as high as $3.8 billion every year.  
 
The current therapy of AD is reactive, where the flares are treated through symptomatic management with 
topical corticosteroids and calcineurin inhibitors. Given that these medications have long-term side-effects, 
and given the chronically relapsing immunopathogenic nature of AD, there is an imperative need for safer 
anti-inflammatory medications.  The aim of this study is to provide clinical performance data to support 
eczema indication claim on package for the PG Ventures medicated skin program. 
A. 
Study Design 
This is an approximately 9-week, 7-visit, randomized, double blind, parallel comparison study consisting of 
a 7-12 day washout phase followed by an 8-week treatment phase.  This study has currently been enrolling 
for approximately 4 months; full enrollment under the initial IRB approved protocol dated October 26, 2017 
has not yet been achieved.  The following changes to the initially approved protocol will be implemented as 
strategies to fully enroll the study as well as to finish the study with a more complete dataset due to a  
higher number of early subject withdraws than was anticipated in the statistical considerations of sample 
size.  Changes to the study population, inclusion criteria, and enrollment strategy from the initial protocol 
are as follows: 
• 
Revise inclusion criteria to the following: 
o 
Omit criteria of VAS, PGA and area coverage (BSA)  
o 
Revise SCORAD criteria to >=18 
o 
All other inclusion criteria (antihistamine use, sun exposure, absence of other clinical 
findings and negative pregnancy test, if applicable) remain the same 
 
• 
In keeping with the current study design of balancing blacks and non-blacks within each of the 
2 test sites, invite back the non-blacks that were previously disqualified, repeat study 
qualification procedures (Screening + washout), and grade these subjects again at Baseline 
against the revised inclusion criteria appearing above. 
 
Note:  Previously disqualified non-black subjects will be scheduled to visit the test 
site(s) en mass, meaning all previously disqualified subjects would be seen within the 
same 1-2 days so that they would be screened and placed on a 7 day washout within 
the same 1-2 days, and return for their Baseline visit within the same 1-2 days.  After 
all “repeat” subjects have completed their Baseline visit, the Sponsor will review their 
visual assessment grades (SCORAD, PGA, EASI) and select subjects for 
randomization into the study using SCORAD criteria >=18 as minimum entrance 
criteria, in accordance with the above revised inclusion criteria.  Subjects will meet all 
other inclusion/exclusion criteria as stated in the Protocol. These subjects may remain 
on washout up to an additional 5 days past the day of their Baseline visit while the 
Sponsor selects subjects for randomization.   
 
• 
Increase the number of subjects randomized into the study from the initial protocol-specified 62 
up to 71 subjects.  
Note:  After review of recruitment observations from this study and data from previous 
studies, these additional 9 subjects that may be enrolled are to be non-black. 
 


Page 4 of 13 
 
This study will now be conducted among up to 71 male and female subjects aged 12 to 65 years old 
(inclusive) and executed by one clinical research company utilizing 2 of their test sites as a strategy to fully 
enroll the study with subjects meeting all revised inclusion/exclusion criteria.  Enrollment of black subjects 
is now capped at the 31 black subjects who have been enrolled.  It will be stipulated that there will only be 
1 grader of record at each of the 2 test sites who will grade all subjects at each site at every time point.   
 
At Screening and Enrollment, subjects deemed qualified for this phase of the study will be provided with 
bar soap and body lotion to use for all their skin cleansing and moisturization needs during the washout 
phase.  Subjects will be instructed to refrain from using any other products on their body (excluding the 
face) including topical corticosteroids, ointments, lotions, sunscreens, etc., must refrain from using 
shampoo or conditioning products that contain known anti-microbial or anti-inflammatory agents (e.g. anti-
dandruff shampoo), and refrain from using any other medications indicated for atopic dermatitis other than 
the study provided products.   Normal facial or hair care products are permitted however they must NOT 
contain anti-bacterial ingredients (e.g. antidandruff shampoo, acne products, etc.). 
 
At Baseline, start of treatment phase, after visual grading (SCORAD, PGA, EASI) has been completed, the 
Sponsor will review subjects’ visual grading data against the revised, minimum inclusion appearing in this 
protocol and Protocol Amendment #001.  Subjects deemed by the Sponsor qualified (communicated via 
email from Clinical Trial Manager to Test Site Study Staff) to participate in this study will have one primary 
lesion and one secondary lesion identified by the Study Dermatologist following the principle that the 
lesions are from the representative affected areas of the body (preferably the primary from limbs), at the 
developing phase, not resolution phase, and 2cm or greater.  All efforts will be made to identify the primary 
lesion from limbs (for individual lesion assessment using extent and severity components of SCORAD), 
and the secondary lesion not having blisters and/or drainage present as determined by the study PI or 
designee (for both individual lesion assessment using extent and severity components of SCORAD and for 
tape stripping procedures). 
 
 
The 4 corners of both the primary and secondary lesions will be marked with “L” brackets using a 
permanent marker.  Subjects will be given a permanent marker and instructed to remark their sites at home 
each time after bathing or showering for the duration of their study participation.  Dermatological lesion 
assessments and imaging of the primary and secondary lesions will be conducted at Baseline, Weeks 2 4, 
and 8.  Subjects will be randomized and balanced into one of the 3 treatment groups based on severity as 
defined by their SCORAD grade.  Treatment groups and a caption of their application regimens are as 
follows:   
 
• 
Desonide will be provided in a tube.  Subjects will be instructed to apply this product only to their 
lesions using the “Finger Tip Method.”  Subjects will also be given a lotion (same as Vehicle) and 
instructed to apply the lotion to the remaining unaffected body skin (whole body including face); 
 
• 
Vehicle and the Sponsor’s experimental cream treatment groups will be provided as a tube and 
lotion (same treatment in both the small treatment tube and the large lotion tube) for blinding 
purposes.  Subject instructions for product application will be the same as for the Desonide group. 
 
Note:  Five minutes after applying both the lesion treatment and lotion products, if desired, subjects 
will be allowed to apply their own facial moisturizer and make up over the study treatments. 
 
To help maintain blinding, products will be concealed in an opaque bag.  Subjects will be instructed to bring 
their products with them in the opaque bag to every visit and to refrain from discussing their study 
participation with other subjects.   Subjects will also be asked to complete a daily diary to record their twice 
daily treatment applications and any medications taken and to bring their diaries with them to every visit.   
 
Study measurements will be conducted at the time points indicated in the table below.  Subjects will 
acclimate with their AD lesion sites exposed to air for at least 30 minutes under office environment 
conditions prior to any study procedures being performed.  Product application and compliance checks as 
well as dermatologic evaluations (incl. AEs) will be conducted at each subsequent visit following Baseline 
to ensure the subject’s condition does not become extensively worse.   For the sake of subject safety, 
subjects who drop from the study will have the reason(s) for their dropping documented, will be asked to 
return their study products and diaries to the test site, and as part of their study exit visit procedures be 
evaluated for SCORAD at the time of their dropping.  Additionally, these subjects, will be asked to continue 
to come to the test site for the remaining study visits for SCORAD evaluations only, if willing, and have 
AE/Medication changes for the remainder of the study documented. 


Page 5 of 13 
 
B. 
Study Schedule (listed in procedure order)  
Study 
Activities 
 
Screen/ 
Enroll, 
start of 
washout 
Base 
line 
WK
1 
WK 
2 
WK  
4 
WK 
 6 
WK  
8 
Study Day 
-7 to -12 
1  
8 
15 
29 
43 
57 
Evaluation Visit(s) 
-1 
1 
2 
3 
4 
5 
6 
Informed Consent/Assent + 
Confidentiality Agreement 
(Appendices IC/Assent + CA) 
X 
 
 
 
 
 
 
Informed Consent for Photo Release- 
declination does not impact 
enrollment (Appendix ICPHOTO) 
X 
 
 
 
 
 
 
INCL/EXCL/DEMO 
(DCF’S INCL, EXCL, DEMO) 
X 
 
 
 
 
 
 
Body system assessment per Test Site 
SOP’s (Appendix SCREENPE)  
X 
 
 
 
 
 
 
Screening labs per Wake SOP’s 
& urine pregnancy test 
(Appendix SCREENLABS) 
X 
X 
X 
X 
X 
X 
X 
Preg-
nancy 
only 
Qualify (DCF QUALIFY) 
X 
 
 
 
 
 
 
Distribute bar soap, lotion for washout 
period (weigh before and after 
distribution) and Subject Instructions 
for the washout period 
(App INWO) 
X 
 
 
 
 
 
 
Acclimate 30-minutes with lesions 
exposed to air (office environment) 
prior to all visual assessments 
 
X 
 
X 
X 
 
X 
Pre-visit Compliance Check & Med Hx 
update/ changes in medications  
(Appendix QVISITPROCEDURES & 
DCF CON-MED) 
 
X 
X 
X 
X 
X 
X 
Query subjects for compliance with 
pre-visit restrictions and instructions 
 
X 
X 
X 
X 
X 
X 
Physician’s Global Assessment, whole 
body (Appendix and DCF PGA) 
 
X 
 
X 
X 
 
X 
SCORAD, Whole Body 
(Appendix and DCF SCORAD) 
 
X 
 
X 
X 
 
X 
SCORAD Lesion Evaluation only, 
extent and severity of primary and 
secondary lesions 
(Appendix SCORAD and DCF SCORAD 
LESION) 
 
X 
 
X 
X 
 
X 
EASI lesion evaluation, whole body 
(Appendix and DCF EASI) 
 
X 
 
X 
X 
 
X 
 
 
Study 
Activities 
(DCF Name) 
(Appendix Name) 
 
Screen/ 
Enroll, 
start of 
washout 
 
 
Base 
line 
 
WK
1 
 
WK 
2 
 
 
WK  
4 
 
 
WK 
 6 
 
 
WK  
8 
Sponsor Review of Visual Grading 
Data for Study Qualification – selected 
subjects approved via email to Test 
Site Staff 
(EASI, SCORAD, PGA) 
 
X 
 
 
 
 
 


Page 6 of 13 
 
III. 
Study Population 
A sufficient number of non-black male and female subjects aged 12-65 (inclusive) diagnosed as having AD and 
otherwise generally healthy will be recruited and/or re-screened if previously disqualified from the general Raleigh, 
North Carolina and Chattanooga, Tennessee populations in order to fully enroll the study with up to 71 subjects.  
Enrollment of black subjects is now capped at the 31 black subjects who have been randomized.  Subjects will be 
recruited based on their ability to meet the inclusion/exclusion criteria and their willingness to comply with all study 
requirements, restrictions and instructions.   
Prior to study start all prospective subjects  
 
 Will read and sign: 
  
-Informed Consent/Assent if underage, Confidentiality Agreement, and Informed Consent for    
              Photo Release (Appendix IC/ASSENT, CA, and ICPHOTO) 
 Will be screened for eligibility to participate based on: 
• 
DCF INCL (all answers must be “yes” to qualify) 
• 
DCF EXCL (all answers must be “no” to qualify) 
• 
DEMO 
• 
DCF CON MED 
• 
SCREENLABS 
• 
QUALIFY    
Qualify (DCF QUALIFY_ADD) 
 
X 
 
 
 
 
 
Identify and mark/remark primary and 
secondary lesions  
(app SITEDIAG) 
 
X 
X 
X 
X 
X 
X 
Medical History and Habits and 
Practices Questionnaire 
(DCF’s H & P and Med Hx) 
 
X 
 
 
 
 
 
Tolerability Questionnaire 
(Appendix and DCF Tolerability) 
 
X 
X 
X 
X 
X 
X 
Dlqi/Poem/Bother/Qol/Self-
Assessment Questionnaires  
(Appendices and DCF SAQ 1) 
 
X 
X 
X 
X 
X 
X 
Consumer OAR Questionnaires 
(DCF SAQ2-1, SAQ2-2, SAQ2-3) 
 
X 
X 
X 
X 
X 
X 
Digital Image of primary and 
secondary lesions (App Imaging) 
 
X 
 
X 
X 
 
X 
Tape Stripping, secondary and 
adjacent non-lesion site (Appendix 
TSSQUAME) 
 
X 
 
X 
 
 
X 
Randomize/distribute test products 
and diaries 
 
X 
 
 
 
 
 
1:1 subject instruction and supervised 
product application coaching session 
 
X 
X 
X 
X 
X 
 
Distribute/collect/review diaries 
weigh products, refresh bar soap prn 
(Appendices DIARY, DCF CON_SUM) 
  
X 
Distrib 
Unit #1  
Treatment  
and lotion  
 
X 
X 
X 
Collect 
Unit #1  
Lotion 
& 
Distrib 
Unit #2  
Lotion 
X 
X 
Final 
collect 
45-minute Consumer Interview, 6-8 
willing subjects selected & interviewed 
by Sponsor rep from 1 test site  
(Appendix Discussion Guide) 
 
 
X 
 
 
 
X 


Page 7 of 13 
 
At Screening and Enrollment, if a prospective subject is admitted or excluded from the study, this 
information will be recorded on DCF QUALIFY.  Enrolled subjects will be given bar soap, lotion, verbal and 
written instructions and restrictions to follow during the washout phase (Appendix INTRWO).   At Baseline, 
if a subject is admitted or excluded from the study, this information will be recorded on DCF 
QUALIFY_ADD.  Qualified subjects at Baseline will be randomized into one of the 3 treatment groups, 
given verbal and written instructions and restrictions to follow, and daily diaries to complete during the 
treatment phase (Appendices INTRTRT and DIARY). 
IV. 
Study Materials 
A. 
Study Products 
The products listed in the table below will be tested during this study.  Test products will be stored in a 
locked room under usual and customary office building conditions.   Unit #1 test products (eczema cream 
and whole body lotion) will be distributed to qualified subjects at Baseline.  Subjects will apply their 
assigned treatments twice daily as directed by their product labels and subject instructions (Appendix 
INTRTRT).   
 
Test Product Regimen 
Rationale 
Observations 
Small tube to apply to lesions twice daily and large lotion 
tube to apply to whole body except lesion sites – same 
product both containers 
Test product 
34 
Small tube to apply to lesions twice daily and large lotion 
tube to apply to whole body except lesion sites – same 
product both containers 
Control Product 
17 
0.05% Desonide (tube) to apply to lesions twice daily in a 
small tube and vehicle lotion in a large tube to apply to 
whole body  
Rx control 
11 
At Weeks 1-6, subjects will be supplied with eczema cream tubes in sequential order (Unit #s 2-6) enough 
to last until their next study visit.   At Week 4, Unit #1 body lotion tube will be collected and subjects will be 
given Unit #2  body lotion to last for the remaining 4 weeks of the study.  All product containers will be 
weighed pre-distribution and after each collection to assess subjects’ consistency of and compliance with 
product usage.   
Supplemental products will be assigned a #5000 series number and will distributed as needed; 
supplemental product numbers will be assigned using the Sponsor’s balance and assignment program.   
B. 
Product Safety Statement 
This study meets the ethical requirements stipulated by the International Conference of Harmonization and 
Guidelines for Good Clinical Practices for Research Involving Human Subjects.  Appropriate safety testing 
has been completed; risk assessments justify the placement of the test products in this study considering 
product concentration(s) and frequency of treatment as set forth in the protocol. 
C. 
Packaging, Labeling, and Shipping of Test Products 
The Sponsor will send all test products directly to the clinical facility prior to the start of the study in 
compliance with current Good Manufacturing Practices.  A sample of how the products will be labeled 
appears in Appendix Label. The quantity of all study material shipped to the clinical facility will be 
documented on a shipping and receiving form, included within the shipment (DCF SHIP_REC).     
D. 
Return of Study Products 
Upon completion of the study, the Investigator or his/her designee will assure that all test products 
(completely used, partially used, or unused) will be returned to the Sponsor at the address listed below.  
Product accountability will be appropriately documented on DCF SHIP_REC.  
 
  
 
The Procter & Gamble Company 
                        Mason Business Center 
  
 
8700 S. Mason Montgomery Rd, DV3 5J5 
  
 
Mason, OH  45040-9462 
  
 
ATTN:  Ryan Nichols 


Page 8 of 13 
 
  
 
Phone:  513-256-1668 
 
V. 
Study Procedures 
 
Study procedures will be performed as presented in the following appendices and at the times indicated in 
the study schedule table listed in Section II.B.     
• 
SCREENPE 
• 
SCREENLABS 
• 
SCORAD 
• 
PGA 
• 
EASI 
• 
SITEDIAG 
• 
DLQI  
• 
POEM  
• 
BOTHER  
• 
IMAGING 
• 
TSSQUAME 
• 
DISCGUIDE 
VI. 
Subject Accountability 
A. 
Subject Identification 
Subjects will be assigned a permanent 4-digit number (consecutive, beginning with #2001) during 
the consent process.  Subjects will be assigned a permanent consecutive randomization number 
(beginning with #201) once they have qualified to participate in the treatment phase of the study. 
B. 
Subject Early Withdrawal  
A subject may voluntarily withdraw from the study at any time for any reason.  If a subject 
experiences a problem that they perceive to be related to study participation, or if test facility 
personnel deem it necessary, the Investigator is responsible to take appropriate action.  The 
Investigator, or designee, will complete a Subject Drop (DCF DROP) form for any subject 
withdrawal or discontinuation prior to the end of the study.  Subjects who withdraw after study 
initiation will not be replaced. 
C. 
Adverse Events 
Subjects will be evaluated at each visit for Adverse Events using the Common Terminology Criteria 
for Adverse Events for Skin & Subcutaneous Tissue Disorders (CTCAE) as outlined in the 
Appendix TOLERABILITY. 
 
The Investigator or designee will complete the DCF AE to record any Adverse Event (AE) that 
occurs during the study, regardless of relationship to treatment.  The Investigator must review and 
sign the completed form associated with each specific AE.   
The Investigator or designee will notify the Clinical Trial Manager within 24 hours of any 
unexpected and/or serious AE’s and notify the IRB within 3 days of any serious adverse events or 
any events that are related to product treatment or study procedures.  The Clinical Trial Manager 
will notify the Study Toxicologist following the Sponsor’s SOP for AE reporting.   In the event of 
multiple adverse events related to test product usage, the Clinical Trial Manager, Clinical Scientist 
& Study Toxicologist will work with the PI to determine the appropriate course of action up to and 
including study suspension. 
D. 
Illness and Medication Reporting 
Subjects will be questioned at each visit about their general health and medications as well as their 
tolerability of the test products (Appendix TOLERABILITY) by a qualified medical professional such 
as a nurse or physician’s assistant.  Any adverse changes to their general health will be recorded 
on DCF AE.  Any changes in their medications (prescription or OTC not previously recorded), will 
be documented as a concomitant medication on the DCF CON_MED form. Responses to the 
tolerability questionnaire will be recorded on DCF TOLERABILITY. 


Page 9 of 13 
 
VIII.   Other Study Documentation 
A.        Protocol Amendments 
If it becomes necessary to modify this protocol, the modification will be documented by a protocol 
amendment.  Amendments will be initiated by the Sponsor and signed by the Investigator or 
designee and by all the appropriate representatives of the Sponsor who are directly impacted by 
the change.  All amendments will be consecutively numbered, describe any changes being made 
and the rationale behind the changes.  Amendments cannot be implemented until written IRB 
approval is obtained.  
B.        Protocol Deviations 
If a significant deviation from the final protocol occurs, it is the responsibility of the Investigator or 
designee to notify the Clinical Trial Manager or designee as soon as possible once the deviation is 
noted and no later than 24 hours after the occurrence.  All deviations and subsequent notification 
will be documented on the Deviation Log (DCF CONDEVERR) for the subject affected.  If a 
deviation affects multiple subjects, it will be recorded on the tab in the eCRF database titled Study 
Notes.   
C.        Study Monitoring 
The Investigator will permit a representative of the Sponsor to visit the facility during the course of 
the study to monitor study progress and to observe all study procedures.  During these visits, the 
Investigator will permit the monitor to inspect all forms and corresponding subjects’ records to verify 
adherence to the protocol.  The study monitor will also be permitted to review and verify test 
materials and any Investigator-generated or Sponsor-generated study documents.  The monitor will 
document and discuss this visit with the Investigator or his designee including any problems that 
are to be resolved. 
D.       Additional Data 
Daily outdoor relative humidity and temperature at the test facility will be recorded during the test 
period on a site provided data collection form.  Acclimation room conditions (temperature controlled 
office environment conditions) will be recorded at 9 am and 3 pm (+/- 1 hour) each study day at 
Baseline, Weeks 2, 4, and  8.   
E. 
Investigator and Site Qualification  
After review of the Investigator’s CV, the Investigator is qualified to conduct this study based on 
education, training, and experience conducting similar studies with similar test products and/or 
methods within the past 2 years.   Further, the Investigator remains in good standing with US 
Governmental agencies regulating the conduct of clinical studies and has agreed via his/her 
signature on Page 1 of this protocol to conduct this study according to GCP/ICH guidelines.  The 
Investigator has agreed to maintain a list of any personnel to which the Investigator delegates 
his/her responsibilities and has agreed that selected delegates will have demonstrated they are 
capable and qualified to perform such functions.  A list of all delegates and their responsibilities will 
be maintained and a copy of this list will be provided to the Sponsor in the Investigator’s final 
report.   
 
The test site has adequate facility space and work processes including current, comprehensive, 
applicable SOP’s, access to sufficient number of prospective subjects meeting the study required 
demographics,  the required equipment and instruments (or Sponsor has agreed to supply), and 
sufficient qualified staff possessing current and applicable training records, the correct skill sets, 
any required professional licensure (Study Physician and assisting health professionals as required 
by state law) to conduct this study in compliance with all Federal, State and local regulations, 
GCP/ICH guidelines, and according to the protocol.  Additionally, the test site has a history of low 
staff turnover which will increase the likelihood that the quality of study and method conduct will be 
sustained over the entire in-life portion of the study.   


Page 10 of 13 
 
VII. 
Data Management and Statistical Analysis 
A. 
Data Collection 
Data entered directly into the Sponsor’s eCRF system will be considered source data.  If an 
independent eCRF database is used (one that is not on the server (i.e., one that is on a dedicated 
instrument computer for direct data capture)), then data will be backed up nightly to another 
storage location (i.e., flash drive, CD, external hard drive, etc.).  This can be done either by using 
the “export all” function under the reports tab and placing the files on a location not on the 
computer or by copying the database to a location not on the computer (i.e., flash drive, CD, 
external hard drive, etc.).  Instrumentation that has a separate data collection system (i.e., not 
eCRF) needs data backed up daily following the directions in the corresponding instrument 
appendix, and this data system will be considered source data.  
 
If the eCRF is not available, all study data will be written directly on the paper CRF as source data 
and recorded into the eCRF when it is available.  It is the responsibility of the Investigator or 
designee to ensure that all source documents and data collection forms are completed, maintained 
according to Good Clinical Practices, and retained in the study records.  This includes assuring that 
all study documents are filled in completely, entered into the eCRF system and 100% Quality 
Control reviewed for accuracy in transcription.       
 
All grading direct data entry errors in the eCRF system will be corrected where possible.  When the 
correction is not possible within the eCRF system the error will be documented in the eCRF 
ComDevErr form.  Included in this error documentation should be the error that occurred and the 
resolution.  Errors to be documented are improperly entered subject numbers, invalid grades or 
instrument data and failure of equipment calibration.  It is the responsibility of the Study Investigator 
or a designee to review the data error record to ensure errors are captured correctly and are easily 
understood.   
B. 
Data Transfer 
Following study completion and prior to submission of the Clinical Study Summary, the test facility 
will give sponsor-requested electronic data files, legible copies of the documents (i.e., DCF’s) not 
entered into electronic format to the Data Manager.  Original source documents reside with the study 
facility. 
C. 
Statistical Analysis  
The Statistical Analysis plan for this study is detailed in Appendix STATS.    
X.    Investigator’s Responsibilities 
A.         Informed Consent / Assent 
Prior to study participation, all subjects will be informed as to the type of study, the procedures to 
be followed, the general nature of the products being tested, and any known or anticipated adverse 
reactions that might result from participation.  Each subject must read, comprehend, and sign the 
informed consent (Appendix IC) before participating in this study.  The informed consent will 
contain all of the basic elements of outlined in ICH E6.  For subjects considered to be “underage” 
following each test site’s state laws, study staff will obtain written documentation of parental 
permission and written documentation of child’s willingness to participate through written assent 
(Appendix ASSENT).   
B.        Final Investigator’s Report 
The Investigator or designee will submit a study report to the Sponsor within 4 weeks following 
study completion or termination.  This report should include:  
• Investigator’s designee of authority statement and signature for specific tasks, e.g., designation 
by investigator to a qualified staff person to enroll subjects. 
• Personnel list of responsibilities (including any non-Test Site Facility personnel) 
• Copy of original Monitor Signature Log and Delegation Signature Log 
• Records of the study site visits by the Sponsor 
• Documentation that the Investigator has reviewed and approved all subject data for the study 
• Documentation by Investigator that all subjects were provided a copy of the Informed Consent 


Page 11 of 13 
 
• Number of subjects screened for eligibility 
• Number of subjects entering and completing the study 
• Number of subjects that withdrew from the study and reasons for withdrawal 
• Any deviations or changes/amendments to the protocol 
• Summary of adverse events 
• Clinical judgments relative to any significant adverse events and their disposition; any alterations 
in treatment due to adverse events 
• Notes to file 
• Data transfer 
• Forms disposition 
• Documentation that source documents transcribed to eCRF have been verified 
• Signed and dated quality assurance statement ensuring protocol compliance 
D. 
Record Retention 
  The Investigator or designees will retain all study records for a minimum of 5 years.  After a minimum 
of 5 years, the test facility will notify the Sponsor before destroying retained study records.     
E. 
Confidentiality 
All information (photographs, medical information and data evaluations, etc.) concerning the 
subject that is obtained in connection with this study will be kept confidential.  The sponsoring 
company, governmental regulatory agencies and the Institutional Review Board (IRB) will have 
access to the study records: however, they will be coded to protect the subject’s confidentiality. 
F. 
IRB Review and Approval  
 
 
The study will not begin prior to the receipt of written confirmation of approval by the IRB and any 
relevant regulatory authority.  It is the responsibility of the Investigator to obtain the IRB approval (per 
the U.S. Code of Federal Regulations, Title 21, Part 56 and applicable ICH guidelines) for the 
protocol, amendments, informed consent, subject information sheet, questionnaires, and advertising 
materials used to recruit study subjects, if appropriate.  A copy of the IRB approval letter along with 
a list of the IRB members who acted on this protocol and a statement that the IRB is in compliance 
with current ICH E6 and Good Clinical Practices (GCP) guidelines will be provided to the Clinical 
Trial Manager. 
It is the Investigator’s responsibility to promptly report to the IRB all changes to the research activity 
and all unanticipated problems involving the risk to human subjects.   
 
XI.   Attachments  
A.    Appendices  
IC/ASSENT  
Informed Consent/Assent for Minors 
ICPHOTO 
Informed Consent for Photo Release 
CA 
Confidentiality Agreement 
FITZSKIN 
Fitzpatrick Skin Type 
SCREENPE 
Body System Assessment (Wake SOP’s) 
CONSENSUS 
Outline of Consensus Grading Activities 
SCREENLABS 
Screening Labs Blood Draw and Urine Pregnancy Test Procedure 
INTRWO 
Subject Instructions for the Washout Phase 
QVISITPROCEDURES Procedures to be Conducted at Every Visit 
SCORAD 
Severity Scoring of Atopic Dermatitis 
EASI 
Eczema Area and Severity Index 
PGA 
Physician’s Global Assessment 
SITEDIAG 
Identify and Mark Lesions & Non-Lesion 


Page 12 of 13 
 
INTRTRT 
Subject Study Instructions for Treatment Phase 
DIARY 
Daily Product Application Diary 
TOLERABILITY 
Instructions for Completion of Tolerability Questionnaire 
DLQI 
Description and Instructions for Completion of Dermatology Life Quality Index 
POEM 
Description and Instructions for Completion of Patient Oriented Eczema Measure 
BOTHER 
Description and Instructions for Completion of Bother Measure 
IMAGING 
Instructions for Obtaining Digital Image of Designated Lesion 
TSSQUAME 
Tape Strip Sampling Procedure 
DISCGUIDE 
Consumer Interview Discussion Guide 
STATS 
Statistical Analysis Plan 
LABEL 
Sample Product Labels 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
B.   Data Collection Forms (DCFs) 
 
INCL 
Inclusion Criteria 
EXCL 
Exclusion Criteria 
DEMO 
Demographics 
CON_MED 
Concomitant Medications 
QUALIFY 
Qualification at Enrollment 
PGA 
Physician’s Global Assessment 
SCORAD 
Severity Scoring of Atopic Dermatitis  
SCORADLESION Objective Severity Scoring of Primary & Secondary Atopic Dermatitis Lesions 
EASI 
Eczema Area and Severity Index 
QUALIFY_ADD 
Qualification at Baseline 
MEDHX 
Medical History 
HAB_PRAC 
Habits & Practices 
SAQ-1 
DLQI / POEM / Bother Questionnaires 
SAQ-2-1, 2-2, 2-3 Consumer Self-Assessment Questionnaire – (OAR) 


Page 13 of 13 
 
TOLERABILITY 
Tolerability Questionnaire 
COMDEVERR 
Comment, Deviation and Error Log 
CON_SUM 
Product Consumption 
DROP 
Subject Drop Form 
AE 
Adverse Event Form 
SHIP_REC 
Ship and Receiving Log 
 
C.  Safety Letter  
 
 
To be provided by the Sponsor.  
 
 
 
 
 

SAP_003.pdf: 
 
 
 
 
 
 
 
 
 
 
 
 
8-Week Atopic Dermatitis (AD) Treatment Study 
NCT03386032 
April 27, 2018 
 
 
 


 
APPENDIX STATS 
STATISTICAL ANALYSIS PLAN 
Study CSD2017168 
 
The Sponsor’s statistician or designee will perform the statistical analyses.   
 
 
A. Study Measurements  
 
Method/Measurement 
Rationale 
Data Collection Time Points 
SCORAD, PGA, EASI, & 
SCORAD Lesion Evaluation  
Atopic Dermatitis Grading, 
Physician’s Global Assessment & 
Lesion Evaluation 
Baseline 
Trt Week 2 
Trt Week 4 
Trt Week 8 
Quality of Life (DQLI, POEM & 
Bother), Self- Assessment and 
Tolerability Questionnaires 
Quality of Life, 
Self- Assessment & Tolerability 
Baseline 
Trt Week 1 
Trt Week 2 
Trt Week 4 
Trt Week 6 
Trt Week 8 
 
Tape Strip 
Skin Barrier/Health Biomarkers 
Baseline  
Trt Week 2 
Trt Week 6 
 
B. Statistical Analysis 
Prior to the breaking of the blind and statistical analysis, all data will be checked for accuracy, completeness, and compliance 
to the study protocol.  Subject evaluations will be checked for compliance to the study protocol regimen and subjects will 
be assessed for compliance to the protocol inclusion/exclusion criteria.  Additionally, investigator comments will be 
assessed for extraneous factors that could affect the usefulness of the subject’s data.  Non-evaluable observations and the 
rationale, along with the method for handling the observations will be documented by the Sponsor prior to unblinding data 
and subsequent analysis of the results. 
The analyses will be performed on the “full analysis set” which is as complete as possible and as close as possible to the 
intention-to-treat (ITT) ideal of including all randomized subjects.  Preservation of the initial randomization in analysis is 
important in preventing bias and in providing a secure foundation for statistical tests.  For those who withdraw prior to 
Week 8, measurements will be made at the time of treatment discontinuation and this observation will be carried forward 
in analyses. This provides estimates of treatment effects that are more likely to mirror those observed in actual practice.  
In addition to the ITT analysis, the analysis will be performed on evaluable subjects only. 
 
1. Analysis Variables 
The following variables will be analyzed to assess treatment efficacy: 
1.) The primary endpoint, change from baseline in dermatologist Severity Scoring of Atopic Dermatitis 
(SCORAD), 
2.) Change in other visual grades of Atopic Dermatitis severity from baseline (PGA, EASI and SCORAD 
lesion evaluation (extent and severity)), 
3.) Change in skin barrier/health biomarkers from Baseline via tape stripping of the secondary lesion site 
and an adjacent unaffected skin site 
4.) Subject self-perception (DLQI, POEM, Bothersome, SAQ)   


 
APPENDIX STATS 
STATISTICAL ANALYSIS PLAN 
Study CSD2017168 
 
Tolerability will be self-assessed and graded by a dermatologist or designee to determine the incidence of treatment 
emergent AE’s.  
Product weights will be collected at all visits to monitor consumption. 
2. Analysis Methods 
Each variable above will be analyzed separately.  For the primary endpoint, superiority of treatment will be assessed 
relative to vehicle control.   
 
For variables that have a continuous distribution, the post treatment evaluations will be analyzed using a mixed model for 
repeated measures with Subject nested within treatment (random effect), and Treatment, Week, Treatment-by-Week, Age 
& Baseline (fixed effects).  A normal plot of the residuals will be examined to assess the assumptions of the model.  
Additionally, the standardized residuals will be assessed for outliers (points that lie far beyond the scatter of the remaining 
residuals, i.e. four or more standard deviations from zero).  Transformations and nonparametric methods may be applied 
to address departures from the distributional assumptions of the mixed model method of analysis and/or for outliers.   
 
For variables that are ordinal categorical, each of the visits will be analyzed separately with a Cochran-Mantel-Haenszel 
test.  Frequency tables will be constructed. 
 
The baseline visit will be analyzed for treatment differences as well. 
 
Summary statistics and/or subgroup analyses will be calculated for each baseline severity (SCORAD), race, age group and 
gender to understand the impact of these on the overall treatment effect. 
 
3. Significance Level 
The type I error rate will be 5% based on a 2-sided test; No adjustments for multiple comparisons will be made for this 
study. 
 
4. Sample Size 
Assuming the most conservative SD=13.2 (Haus study), a sample size of 26 for treatment and 13 for control (2:1 
randomization) will provide 80% power to detect a difference in change in SCORAD from baseline of 12.9 (two-sided test 
with type I error rate of 5%).  A sample size of 8 for positive control and 13 for control will provide 80% power to detect a 
difference of 17.5. 
 
The sample size will be inflated 30% to 62 for dropouts (34 randomized to Treatment, 17 to Control and 11 to Positive 
Control).  Note for perspective, a clinically important difference is 8.7 units..(1) 
 
5.   Treatment Randomization  
Treatment assignment will be randomized to subject to balance for baseline AD severity (SCORAD Moderate or Severe) 
and race (Black and Non-black) within each site.  
6. Interim Analysis 
 
This study requires rolling enrollment to meet the target base size with 50% severe subjects and may cause a delayed 
completion.  At a certain date, if the study remains ongoing, there may be a business need to conduct an interim analysis.  
The purpose of this request is to understand the probability of success so that leadership can make the capital investment 
to meet the scheduled Global Business Plan timeline.  Management will initiate the conduct of an interim analysis by 
signing a memo (separate from the protocol) outlining the risks, timing, principles, process and resources associated with 
an interim analysis.   
 


 
APPENDIX STATS 
STATISTICAL ANALYSIS PLAN 
Study CSD2017168 
 
The interim analyses will be conducted on available data for completed subjects (including dropouts).  Database lock is 
not required for interim analysis.  However, these data will be checked for accuracy and completeness and evaluability for 
these completed subjects will be determined and incorporated into the interim analysis.  The project statistician will be the 
only person with authority to break the blind for interim analysis of data.  The project statistician will no longer be 
involved in any evaluability discussions after the interim analysis.  All other team members will remain blinded.  Only the 
statistical analysis for the primary endpoint of SCORAD will be performed.  Only summary results will be shared with the 
PGV leadership through a written communication (i.e. summary statistics and results).  No un-blinded subject level data 
will be made available to anyone besides the statistician.  No information will be shared with the rest of the clinical team 
supporting this project.   
 
References: 
(1) Schram, ME, Spuls, PI, Leeflang, MMG, Lindeboom, R, Bos, JD, Schmitt, J.  EASI, (objective) SCORAD and POEM 
for atopic eczema:  responsiveness and minimal clinically important difference.  Allergy 2012; 67: 99-106.