Conditions: Atopic Dermatitis
Keywords: AD
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 91
Healthy volunteers: no

Brief summary:
This study determines the Maximum Tolerable Dose (MTD) by maximum BSA percentage treated and evaluates safety and efficacy of 1.1% w/w AMTX-100 CF versus placebo (vehicle).

The study has two parts:

Phase I (Part 1):

Approximately Twenty-five (25) subjects with various treatable Body Surface Area (BSA) involvement of Mild to Moderate Atopic Dermatitis will be enrolled in the study and treated with 1.1% w/w AMTX-100 CF.

Phase II (Part 2):

Approximately sixty (60) subjects with Mild to Moderate Atopic Dermatitis with various treatable BSA involvement of Mild to Moderate Atopic Dermatitis will be randomized to be treated with 1.1% w/w AMTX-100 CF3 concentration or Vehicle (Placebo) in the study.

Detailed description:
AMTX-100 CF3 drug product is formulated as a water-based, topical cream incorporating a 28-amino acid synthetic polypeptide (AMTX-100) as the active pharmaceutical ingredient (API). AMTX-100 is a chimeric, cell-penetrating, bifunctional nuclear transport modifier (NTM), that is engineered to modulate nuclear transport of transcription factors (NF-κB, NFAT, AP-1, and STAT1) involved in the activation of gene expression of key mediators of inflammation (TNFα, IL-1β, IL-6, IL-17, MCP-1, etc.) and metabolic syndrome (ChREBP and SREBP) by importin α/β complex and importin β, respectively. This further leads to a reduction in pro-inflammatory cytokine/chemokine production and lipid and carbohydrate metabolic products.

AMTX-100 CF3 is intended to improve symptoms associated with mild to moderate Atopic Dermatitis in adults. This Phase I/II study aims to determine the Maximum Tolerable Dose (MTD) by maximum BSA percentage treated and to evaluate efficacy of 1.1% w/w AMTX-100 CF3 versus placebo (vehicle).

Arms:
arm 1: Open-label, five (5) cohorts were sequentially enrolled. AMTX-100 CF 1.1% w/w, topically applied twice a day for 7 consecutive days to all treatable AD affected areas from 3% to 70% of the Body Surface Area (BSA) (3% BSA ≤ AD Affected Area ≤ 70% BSA) arm 2: AMTX-100 CF3 (1.1% w/w), topically applied twice a day for 28 consecutive days to all treatable AD affected areas arm 3: Placebo (Vehicle) (0% w/w), topically applied twice a day for 28 consecutive days to all treatable AD affected areas

Interventions: intervention 1: 1.1% w/w AMTX-100 CF-part1 intervention 2: Placebo intervention 3: 1.1% w/w AMTX-100 CF3-part2
Intervention descriptions: intervention 1: AMTX-100 CF, topical cream with 1.1% w/w active pharmaceutical ingredient intervention 2: Topical cream manufactured to mimic AMTX-100 CF3 intervention 3: AMTX-100 CF3, topical cream with 1.1% w/w active pharmaceutical ingredient

Protocol document:
SAP_002.pdf: 
STATISTICAL ANALYSIS PLAN  
FOR PART 1 USING PROTOCOL AMTX100-AD-01 
Sponsor:
Protocol Number: 
Protocol Title: 
Amytrx Therapeutics, Inc.  
AMTX100-AD-01 (NCT04313400)
A Two part, Phase I/II, Multi-center, Double-Blind, 
Randomized, Vehicle-controlled Study of the Safety and 
Efficacy of topically applied AMTX-100 CF in adult patients 
with Mild to Moderate Atopic Dermatitis 
Protocol Version / Date: 
Final Version 2.0/ 20 Jan 2020 
SAP Author: 
Amarex Clinical Research,
LLC 
20201 Century Boulevard 
Germantown, MD   20874 
USA 
Telephone:   1-866-AMAREX-1 
1-301-528-7000
Facsimile: 
1-301-528-2300 
Plan Version: 
Part 1 Version 1.0 
Plan Date: 
16Sep2021 
--- confidential--- 


Protocol: AMTX100-AD-01 
Statistical Analysis Plan for Part 1 
Amytrx Therapeutics, Inc. 
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Protocol Number:  
AMTX100-AD-01 
Protocol Version / Date: 
Final Version 2.0/ 20 Jan 2020 
Protocol Name: 
A Two part, Phase I/II, Multi-center, Double-Blind, 
Randomized, Vehicle-controlled Study of the Safety and 
Efficacy of topically applied AMTX-100 CF in adult 
patients with Mild to Moderate Atopic 
 
Sponsor: 
Amytrx Therapeutics, Inc. 
Prepared by: 
Amarex Clinical Research 
20201 Century Boulevard 
Germantown, Maryland  20874 
SAP Version: 
Part 1 Version 1.0 
SAP Date: 
16Sep2021 
 
 
I have read and approve the Statistical Analysis Plan specified above and agree on its content: 
 
 
 
 
Statistician, Amarex Clinical Research 
 
Date 
 
 
 
SPONSOR Representative 
 
Date 


Protocol: AMTX100-AD-01 
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Amytrx Therapeutics, Inc. 
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TABLE OF CONTENTS 
 
Section   
Page 
ABBREVIATIONS, ACRONYMS, AND DEFINITIONS.................................................................. 5 
1. 
INTRODUCTION................................................................................................................ 7 
2. 
PROTOCOL DESIGN ......................................................................................................... 7 
2.1 
Design Overview ...................................................................................................... 7 
2.2 
Cohorts .................................................................................................................. 12 
2.3 
Randomization and Stratification ............................................................................. 12 
2.4 
Blinding ................................................................................................................. 12 
2.5 
Protocol Objective(s) .............................................................................................. 12 
Secondary Objective ............................................................................................... 12 
2.6 
Efficacy Assessments/ Outcome Measures ................................................................ 13 
3. 
SAMPLE SIZE DETERMINATION, STATISTICAL POWER, AND SIGNIFICANCE LEVEL
........................................................................................................................................... 13 
4. 
INTERIM ANALYSIS ....................................................................................................... 13 
5. 
PRIMARY HYPOTHESIS TO BE TESTED ..................................................................... 13 
6. 
ANALYSIS POPULATIONS ............................................................................................. 14 
6.1 
Safety Population .................................................................................................... 14 
7. 
DATA CONVENTION AND RELATED DEFINITIONS .................................................. 14 
7.1 
Baseline Definition ................................................................................................. 14 
7.2 
Duplicate Data ........................................................................................................ 14 
7.3 
Outliers .................................................................................................................. 14 
7.4 
Handling of Missing Data ........................................................................................ 14 
7.5 
Multicenter Clinical Trials ....................................................................................... 14 
7.6 
Multiple Comparisons and Multiplicity ..................................................................... 14 
7.7 
Covariates and Prognostic Factors ............................................................................ 14 
7.8 
Subgroups .............................................................................................................. 14 
7.9 
Standard Calculations .............................................................................................. 15 
7.9.1 
Age .......................................................................................................... 15 
7.9.2 
Change from baseline ................................................................................. 15 
7.9.3 
Percent Change from Baseline .................................................................... 15 
8. 
STATISTICAL METHODS ............................................................................................... 15 
8.1 
Summarizing Disposition and Baseline Data ............................................................. 15 
8.1.1 
Subject Disposition and Withdrawals .......................................................... 15 
8.1.2 
Protocol Deviations .................................................................................... 16 
8.1.3 
Demographics and Baseline Characteristics ................................................. 16 
8.1.4 
Prior and Concomitant Medications ............................................................. 16 
8.1.5 
Extent of Exposure .................................................................................... 16 
8.1.6 
Study Treatment Compliance ...................................................................... 16 
8.2 
Analysis of Safety Data ........................................................................................... 16 
8.2.1 
Adverse Events .......................................................................................... 17 
8.2.2 
Application Site Reaction ........................................................................... 17 
8.2.3 
Clinical Laboratory Evaluations .................................................................. 18 
8.2.4 
Vital Signs ................................................................................................ 18 
8.2.5 
Physical Examination ................................................................................. 19 




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ABBREVIATIONS, ACRONYMS, AND DEFINITIONS 
Abbreviation/Acronym 
 
Definition 
AD 
AE 
ANCOVA 
ASA 
BMI 
BP 
BSA 
CI 
CM 
CRF 
CRO 
CTCAE 
DLQI 
DLT 
DSMC 
EASI 
eCRF 
FDA 
IA 
ICF 
ICH 
IDMC 
ITT 
IWRS 
MedDRA 
MTD 
NRS 
PI 
PT 
QOL 
 
Atopic Dermatitis  
Adverse Event 
Analysis of Covariance 
American Statistical Association 
Body Mass Index 
Blood Pressure 
Body Surface Area 
Confidence Interval  
Concomitant Medications 
Case Report Form 
Contract Research Organization 
Common Terminology Criteria for Adverse Events 
Dermatology Life Quality Index 
Dose-Limiting Toxicity 
Data Safety Monitoring Committee  
Eczema Area and Severity Index 
Electronic Case Report Form 
U.S. Food and Drug Administration 
Interim Analysis 
Informed Consent Form  
International Council on Harmonization  
Independent Data Monitoring Committee 
Intent-to-Treat  
Interactive Web Randomization System 
Medical Dictionary for Regulatory Activities  
Maximum Tolerable Dose 
Pruritus Numerical Rating Scale  
Principal Investigator 
Preferred Term level of MedDRA 
On Quality of Life 


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Abbreviation/Acronym 
 
Definition 
SAE 
SAP 
SAS® 
SOC 
SOP 
TCS 
TEAE 
USA 
vIGA-AD 
 
WHO 
Serious Adverse Event 
Statistical Analysis Plan 
Statistical Analysis System 
System Organ Class  
Standard Operating Procedure 
Topical corticosterioids 
Treatment-emergent Adverse Event 
United States of America 
Validated Investigator Global Assessment for Atopic 
Dermatitis 
World Health Organization 


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1. 
INTRODUCTION 
This Statistical Analysis Plan describes the planned analyses and reporting for the Phase I (Part 1) 
clinical trial protocol AMTX100-AD-01, conducted by Amytrx Therapeutics, Inc. The reader of this 
Statistical Analysis Plan (SAP) is encouraged to review the complete protocol and amendments as 
this plan contains only a limited overview of protocol information.  The main objectives of this plan 
are to provide details pertaining to statistical methodology, data conventions, and processes used for 
the analysis of data from this trial.  
The format and content of this SAP are structured to provide sufficient detail to meet the requirements 
specified by the International Council on Harmonization (ICH) E9: Guidance on Statistical Principles 
in Clinical Trials.  All work planned and presented in this Statistical Analysis Plan will follow the 
ethical guidelines published by the American Statistical Association (ASA). 
The following documents were reviewed in preparation of this Statistical Analysis Plan: 
• Final protocol 2.0/ 20 Jan 2020 
• ASA Ethical Guidelines for Statistical Practice (2016) 
• The Royal Statistical Society: Code of Conduct (2014) 
• ICH Guidance on the Structure and Content of Clinical Study Reports (ICH E3, 1996) 
• ICH Guidance on the Structure and Content of Clinical Study Reports (ICH E3(R1), 2013) 
• ICH Guidance on the Statistical Principles for Clinical Trials (ICH E9, 1998) 
• ICH Guidance on the Statistical Principles for Clinical Trials (ICH E9(R1), 2017) 
2. 
PROTOCOL DESIGN 
2.1 
Design Overview 
This is an adaptive, Phase I study: Part 1 (Maximum Tolerable Dose (MTD) Finding by maximum 
percentage of BSA treated).  
Part 1 of this study is an open-label, dose escalation study of the safety and tolerability of topically 
applied AMTX-100 CF in adult patients with mild to moderate AD. Part I of this study is designed 
to determine the MTD of AMTX-100 CF (1.1% w/w concentration) for the highest treated percentage 
of the BSA affected with AD. The MTD is defined as 1 cohort dose level below the dose, in which 
dose limiting toxicities (DLTs) as defined below were observed. In total, five (5) cohort dose levels 
will be tested sequentially by escalating applications of AMTX-100 CF 1.1% to higher percentages 
of BSA affected with AD at each cohort. Each enrolled subject will receive the assigned dose of 
Open-label AMTX-100 CF 1.1% w/w to be applied twice daily to all treatable lesions of AD 




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Protocol: AMTX100-AD-01 
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Assuming no DLTs occur at any cohorts, in Part 2 (Phase II) of the study, three dose concentrations 
(low doset-treatment safety. concentration (0.11% w/w), medium dose concentration (0.33% w/w) 
and high dose concentration (1.1% w/w)) of AMTX-100 CF will be further evaluated for safety and 
efficacy, compared to placebo (vehicle), in adult patients with mild to moderate AD, with up to 70% 
treatable BSA involvement. 


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w/w concentration) in improving symptoms associated with mild to moderate Atopic 
Dermatitis in adults. 
2.6 
Efficacy Assessments/ Outcome Measures 
2.6.1.1 Primary Outcome Measure  
• Maximum Tolerable Dose (MTD) by maximum percentage of BSA treated, by evaluation of 
dose-limiting toxicity (DLT) of AMTX-100 CF (1.1% w/w concentration) based on the safety 
profile 
2.6.1.2 Safety Outcome Measures 
• Incidence of Treatment-Emergent Adverse Events (TEAE) 
• Incidence of withdrawals from the study due to TEAEs 
• Changes in study treatment application site reaction assessment 
• Changes and shifts in laboratory measurements over time 
• Changes in vital signs over time 
 
 
 
 
 
3. 
Sample Size Determination, Statistical Power, And Significance Level 
The sample size of 25 subjects (5 subjects per cohort) for Phase I of this study is selected on the basis 
of clinical judgment and not based on statistical power calculation. The number of subjects is deemed 
adequate to provide clinically meaningful descriptive results consistent with study objectives.  
4. 
INTERIM ANALYSIS 
 
 
 
 
 
 
5. 
PRIMARY HYPOTHESIS TO BE TESTED 
There is no formal hypothesis testing for this study as the study is a Phase I evaluation and is not 
intended to be hypothesis generating. The study is not powered to reliably yield statistically 
significant conclusions. 


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6. 
ANALYSIS POPULATIONS 
 
 
 
  
7. 
DATA CONVENTION AND RELATED DEFINITIONS   
 
 
  
 
  
 
 
  
 
 
 
 
 
 
7.4 
Handling of Missing Data  
All efforts will be made to avoid missing data; however there will be no imputation of missing data 
for this early phase study and all summaries will be based on observed data only       
7.5 
Multicenter Clinical Trials  
This is a multi-center clinical trial. 
 
 
 
 
 
 
 
  
7.8 
Subgroups  
There is no prespecified subgroup analysis for this study. Subgroup analysis may be conducted as 
needed. 


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7.9 
Standard Calculations  
 
  
 
  
 
 
 
 
 
8. 
STATISTICAL METHODS 
All statistical analyses will be performed using SAS® for Windows, version 9.4 or later. All data 
collected during this study will be presented in subject data listings.  
  
 
 
 
8.1 Summarizing Disposition and Baseline Data  
8.1.1 Subject Disposition and Withdrawals 
There will be a detailed accounting of all subjects who sign an informed consent to participate in this 
trial. The following will be summarized by cohort:   
 
 
 
 
 
 
 
  
 
 
 
  
 
 
   


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8.1.2 Protocol Deviations 
Protocol deviations for all randomized subjects will be listed as by-subject listing and deviations will 
be summarized descriptively according to the following categories:  
 
 
 
 
 
 
 
 
8.1.3 Demographics and Baseline Characteristics 
Demographics and baseline characteristics (including age, race, gender, Ethnicity, Height, Weight, 
BMI and BSA etc.) will be presented as by-subject listing and summarized by cohort. 
Atopic dermatitis history and medical history will be provided as by-subject listings.  
8.1.4 Prior and Concomitant Medications 
Prior medication is defined as any medications with an end date prior to the first treatment date. 
All prior and concomitant medications recorded in the case report form will be listed and coded to 
the drug substance level (i.e., generic term) using the most recent version of WHO Drug dictionary, 
and summarized by cohort and by the number and percentage of subjects taking each medication for 
the Safety population.  
8.1.5 Extent of Exposure  
All treatment administration data will be listed and summarized for the Safety population.  
The extent of exposure will be summarized descriptively.  
 
  
8.1.6 Study Treatment Compliance   
 
 
  
8.2 
Analysis of Safety Data 


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All safety analyses will be conducted using the Safety population. All data collected will be 
summarized according to the variable type. No inferential statistics are planned.  
8.2.1 Adverse Events 
Adverse events will be classified by system organ class (SOC) and preferred term (PT) according to 
the most recent version of MedDRA dictionary.     
TEAE are defined as adverse events with onset date on or after the first treatment. TEAEs will be 
summarized by cohort, System Organ Class, and preferred term. The following TEAE summaries 
will be provided: 
 
  
 
 
 
 
 
 
   
All adverse events recorded in the eCRF will be presented as by-subject listings. 
8.2.2 Application Site Reaction 
Local skin reactions will be assessed in all areas treated with study drug and graded by the investigator 
on a scale of 0 to 4 based on the area with the most severe skin reaction among all treated areas. A 
grade of 0 represents no reaction, and a grade of 4 indicates a marked and severe skin reaction that 
extended beyond the treated areas.  
 
 
 
 
  
 
 


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8.2.3 Clinical Laboratory Evaluations  
All results of laboratory evaluations will be presented as by-subject listings. 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.2.4 Vital Signs 
Vital sign assessments are performed in order to characterize basic body function. The parameters 
collected in this study are: systolic BP (mmHg), diastolic BP (mmHg), temperature (0C), heart rate 
(bpm), respiratory rate (bpm).   
  
 
 


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8.2.5 Physical Examination  
  
 
 
 
 
 
 
 
 
 
 


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8.2.6 Urine Pregnancy Test 
All data from Urine Pregnancy test will be presented as a by-subject listing.  
  
 
 
 
 
  
 
 




Protocol: AMTX100-AD-01 
 
                               Statistical Analysis Plan for Part 1 
Amytrx Therapeutics, Inc. 
 
 
 
 
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X 
 
X[1] 
X 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
2nd dose (PM) on Day 0, then 
BID through Day 6 
 
 
 
X[2] 
X 
 
 
 
 
X 
 
 
 
X[1][2] 
X 
X 
 
 
X[2] 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 


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10. APPENDIX 2 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


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10.2 Planned Summary Tables  
 
 
 
 
  
  
  
 
  
 
 
 
 
 
 
 


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11. 
REFERENCES 
1. ASA Ethical Guidelines for Statistical Practice (2016) 
2. The Royal Statistical Society: Code of Conduct (2014) 
3. ICH Guidance on the Structure and Content of Clinical Study Reports (ICH E3, 1996) 
4. ICH Guidance on the Structure and Content of Clinical Study Reports (ICH E3(R1), 
2013) 
5. ICH Guidance on the Statistical Principles for Clinical Trials (ICH E9, 1998) 
6. ICH Guidance on the Statistical Principles for Clinical Trials (ICH E9(R1), 2017) 
7. Badia X, Mascaro JM, et al. Measuring health-related quality of life in patients with 
mild to moderate eczema and psoriasis: clinical validity, reliability and sensitivity to 
change of the DLQI. Br J Dermatol 1999; 141:698-702. 
8. Basra MK, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the Minimal 
Clinically Important Difference and Responsiveness of the Dermatology Life Quality 
Index (DLQI): Further Data. Dermatology. 2015;230(1):27-33. 
9. Eli Lilly and Company. Validated Investigator Global Assessment for Atopic 
Dermatitis 
(vIGA-AD™). 
International 
Eczema 
Council 
2017; 
http://www.eczemacouncil.org/wp-content/uploads/2018/02/Validated-Investigator-
Global-Assessment-Scale_vIGA-AD_2017.pdf 
 
 
 


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12. 
VERSION HISTORY  
Version 1 
This is the first version of this document. 
 

ICF_003.pdf: 
Amytrx Therapeutics, Inc./ Protocol Number AMTX100-AD-01 
Page 1 of 21  
«PiFullName» 
Advarra IRB Approved Version 27 Feb 2020 
Revised «PIApprovalDate» 
INFORMED CONSENT FORM AND AUTHORIZATION TO DISCLOSE HEALTH 
INFORMATION (Part 1) 
Sponsor / Study Title: 
Protocol Number: 
Principal Investigator: 
(Study Doctor) 
Telephone: 
Address: 
Amytrx Therapeutics, Inc./ “A Two part, Phase I/II, Multi-
center, Double-Blind, Randomized, Vehicle-controlled Study 
of the Safety and Efficacy of topically applied AMTX-100 
CF in adult patients with Mild to Moderate Atopic 
Dermatitis” 
AMTX100-AD-01 (NCT04313400)
«PiFullName» 
«IcfPhoneNumber» 
«PiLocations» 
This consent form contains important information to help you decide whether to 
participate in a research study. 
The study staff will explain this study to you. Ask questions about anything that is not clear at 
any time. You may take home an unsigned copy of this consent form to think about and discuss 
with family or friends. 
➢This consent is for Part 1 (Phase 1) of clinical research study, AMTX100-AD-01.
➢The Part 1 (Phase 1) of the study AMTX100-AD-01, is the first study in which the study
drug, AMTX-100 CF topical cream, is given to humans.
➢Being in this study is voluntary – your choice.
➢If you join this study, you can still stop at any time.
➢No one can promise that a study will help you.
➢Do not join this study unless all of your questions are answered.
After reading and discussing the information in this consent form you should know: 
•
Why this research study is being done;
•
What will happen during the study;
•
Any possible benefits to you;
•
The possible risks to you;
•
Other options you could choose instead of being in this study;


Amytrx Therapeutics, Inc./ Protocol Number AMTX100-AD-01  
Page 2 of 21   
  
«PiFullName» 
Advarra IRB Approved Version 27 Feb 2020 
Revised «PIApprovalDate» 
 
• 
How your personal health information will be treated during the study and after the study is 
over; 
• 
Whether being in this study could involve any cost to you; and 
• 
What to do if you have problems or questions about this study. 
 
Please read this consent form carefully. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time.  
(21CFR 50.25(c)). 
 
Introduction 
 
You are being invited to take part in Part 1 (Phase 1) of this clinical research study because you 
have been diagnosed with atopic dermatitis (also known as eczema), a skin condition that makes 
your skin red, dry and itchy.  
 
The name of the study drug involved in this Part 1 (Phase 1) of the study is: 
• AMTX-100 CF, topical cream, 1.1%  
 
For purposes of this research, you will be referred to as a “participant”.   
 
Amytrx Therapeutics, Inc. (Amytrx), a pharmaceutical company based in US, is supporting this 
research study by providing study drug and funding for this research study. 
 
Before you decide to take part in this study, it is important for you to understand why the 
research is being done and what it will involve. This consent form may contain words that you 
do not understand. Please take the time to read the following information carefully and feel free 
to take home an unsigned copy of this consent form to discuss this information with your family, 
friends, relatives and/or your study doctor or other primary care physicians (PCP). Please ask the 
study doctor or one of the study staff to explain any words or information that you do not clearly 
understand. Feel free to request more information about the study.  
 
Once you have this information, understand the study procedures, and have had all your 
questions answered, you will need to decide if you will participate in this study. If you decide to 
participate, you will be asked to sign and date this consent form. Signed and dated copies of the 
consent form will be provided to you. You cannot take part in this research study until you sign 
and date this consent form. 
 
Advarra IRB has approved the information in this consent document and has given approval for 
the study doctor to do the study.  An institutional review board (IRB) is an independent 
committee established to help protect the rights of research subjects.  This does not mean the 
IRB has approved your participation in the study.  You must think about the information in this 
consent document for yourself.  You must then decide if you want to be in the study. 
 


Amytrx Therapeutics, Inc./ Protocol Number AMTX100-AD-01  
Page 3 of 21   
  
«PiFullName» 
Advarra IRB Approved Version 27 Feb 2020 
Revised «PIApprovalDate» 
 
What is the purpose of the study? 
 
Your study doctor and his/her colleagues are conducting a research study with Amytrx 
Therapeutics, Inc. (Amytrx) to evaluate whether the study drug (AMTX-100 CF, topical cream, 
1.1%) is safe and efficacious when used to treat Atopic Dermatitis (eczema). Atopic dermatitis 
(eczema) is a condition that makes your skin red, dry and itchy. This study drug is investigational 
because it has not been approved by the U.S. Food and Drug Administration (FDA). The results 
of these studies will be used to design future studies to improve treatment of atopic dermatitis. 
 
The Part 1 (Phase 1) of the study will look at how safe different doses of the investigational drug 
AMTX-100 CF, topical cream, 1.1%, work in improving symptoms of atopic dermatitis. This 
Part 1 (Phase 1) of the study, AMTX100-AD-01, is the first study in which the study drug, 
AMTX-100 CF topical cream, is given to humans. Previous animal studies and pre-clinical work 
have shown that the study drug is both effective in treating eczema like lesions on animals, and 
safe at the dose which you will receive which is much lower than the doses the animals have 
received, however, it is unknown how safe and how well different doses of the investigational 
drug AMTX-100 CF topical cream, 1.1%, will work in human participants with atopic dermatitis 
at this time.  
 
How does AMTX-100 CF  work? 
 
Atopic Dermatitis (AD) is a common, chronic, non-infectious skin condition. The main symptom 
of this inflammatory disease is a very itchy rash. The itch leads to scratching, and more redness, 
swelling, cracking, leaking clear fluid, crusting, and scaling. 
 
In many cases AD gets better as the years go by, and it may go away for a while or disappear 
altogether. AD flare-ups (getting worse at times) however can really affect quality of life. People 
with AD tend to have an over-reactive immune system that when triggered by a substance 
outside or inside the body, responds by producing inflammation. It is this inflammation that 
causes the red, itchy and painful skin symptoms.  
 
AMTX-100 CF study drug product is a white cream with AMTX-100, a new class of medicines 
which target body’s inflammatory responses. AMTX-100, the active ingredient, is a peptide (a 
type of protein), which reduces the inflammatory responses within your skin cells, thus reducing 
eczema symptoms. In Part 1 of the study, AMTX-100 CF topical cream will be applied to the 
eczema affected areas of your skin twice daily for seven (7) consecutive days.  
 
This document uses words such as study treatment, study drug, medication, and participant. Please 
remember this is a research study and the use of these terms does not mean the use of AMTX-100 
CF has been found to be safe or effective for your condition. 
 
Why have I been chosen? 
 
You have been chosen for consideration for this study because you are diagnosed with atopic 
dermatitis (AD), also known as eczema, and your study doctor thinks that you might be a good 
candidate for Part 1 of this study, based on how severe and how large your skin areas are 


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affected by AD. In Part 1 (Phase 1) of the study, about 25 participants with atopic dermatitis will 
enroll at about 5 sites within the United States. 
 
Do I have to take part? 
 
You do not have to take part in this study; it is completely voluntary. You will always be free to 
withdraw from the study at any time. If you withdraw during the study, you will be asked to 
come in for a final visit for study evaluations. You do not have to give a reason for your 
withdrawal from the study. This will not affect the standard of care that you will receive, and it 
will not result in any penalty or loss of benefits to which you are entitled. The data collected up 
to that point will be kept with your medical records and will be kept confidential. Your identity 
will not be disclosed. 
 
General Study Design and Duration of Study Involvement 
 
Part 1 of the study is designed to determine how much of the study drug, AMTX-100 CF topical 
cream, 1.1%, is safe to be used on body surface areas affected with AD. 
 
The duration of your participation in Part 1 (Phase 1) of this study will be approximately up to 
six (6) weeks and include four (4) in-clinic study visits to the study center and one (1) 
participation confirmation call by telephone . The study will be conducted in 3 Parts. After the 
initial screening period of the Part 1 study (up to 3 weeks), you will enter study treatment period 
of the Part 1 study (7 days), followed by follow-up period of the study (around 2 weeks). During 
the study treatment period, fourteen (14) doses of AMTX-100 CF topical cream, 1.1%, will be 
applied to all the AD-affected areas as instructed by the study doctor, twice daily for 7 
consecutive days, regardless of whether your AD affected skin areas become better or clear.  
 
There are five (5) different dose levels of AMTX-100 CF topical cream, 1.1%, that will be 
administered in this study. The dose level (group) that you will be assigned to will depend on 
timing, how large your AD affected areas are, and per the study doctor determination: 
 


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*Participant will be eligible to unique dose level, depending on how large the skin areas involved 
with atopic dermatitis is. 
 
**Amount of AMTX-100 CF topical cream, 1.1%, will be applied to all treatable AD affected 
areas on your skin, depending on how large your skin areas involved with atopic dermatitis is. 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
NOTE:  
The study doctor will conduct dermatologic evaluations on you to evaluate your symptoms of 
atopic dermatitis on each clinical visit. These evaluations will include questionnaires, assessment 
scales and pictures of AD affected skin areas to confirm the atopic dermatitis diagnosis and, 
determine how severe symptoms of atopic dermatitis are.  
 
The questionnaires, assessment scales and pictures will not include any identifying information 
about you (name, address, phone number, physical appearance, etc.), but will be labeled with a 
unique subject ID number assigned to you to protect confidentiality and some of them may be 
uploaded to a secure internet portal. The applicable study team members will need specific login 
credentials to be able to access the questionnaires, assessment scales and pictures on this secure 
internet portal. No one other than the study team will have access to this portal. The 
questionnaires, assessment scales and pictures may be used by the study Sponsor (Amytrx 
Therapeutics, Inc) or people or companies working with the Sponsor for research purposes only 
as described above and will not be sold to other people or companies for commercial purposes. 
De-identified pictures may or may not be used in future publication. The questionnaires, 
assessment scales and pictures uploaded to the secure internet portal will be destroyed 
immediately after study analyses completion.  
 
Your Responsibilities 
As a participant, your responsibilities include: 
• Follow your study doctor’s or study staff’s instructions 
• Ensure that you keep your appointments for all visits; 


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• Ensure that you apply a thin layer of assigned amount of study drug, AMTX-100 CF 
topical cream, to all assigned AD-affected areas, twice daily for 7 consecutive days 
(thirteen (13) doses in total at home) throughout the study, as instructed by the study 
staff; 
• While you apply study drug, 
o Avoid removing or occluding the study treatment by wearing loose-fitting 
clothing;  
o Avoid wiping your skin; 
o Avoid swimming after application; 
o Bathing the treated areas will be allowed once daily and should be done at least 
every 3 days; 
o Bathing/washing the treated areas in between morning and evening dose should 
be avoided within 8 hours after application; 
• You may have some help from others when you apply AMTX-100 CF topical cream for 
skin areas which are hard to reach. 
• Record study treatment administration information in patient diary, as instructed by the 
study staff, and return patient diary and used study drug tubes to site; 
• You may use basic moisturizers/emollients to non-study drug treated skin areas (skin 
areas where study drug cream is not applied); 
• Report any changes in your health or medications to the study doctor. You should not 
make any changes in your medications for atopic dermatitis unless instructed by the study 
doctor. In case your study doctor initiates any treatment for worsening symptoms of 
atopic dermatitis, ensure that you follow the treatment, instructed by the study doctor;  
• There will be no restriction of what you can eat during the study, unless food items 
known to yourself or study doctor to trigger AD symptoms; 
• If you are a woman of child bearing potential, you must use an acceptable method of 
birth control (for example, diaphragm, intrauterine device (IUD), condom, hormonal 
contraceptives, or abstinence) during your participation in the study or be surgically 
sterile (for example, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), so 
that you do not become pregnant. If you are found to be pregnant after you receive first 
dose of study drug, your participation in the study will be terminated, but your pregnancy 
will be followed up to term to evaluate if there are any safety concerns with you or your 
child. 
• If for any reasons you are withdrawn from the study, withdrawal visit and follow up visit 
assessments will be performed. 
 
Research Study Visits, Procedures and Assessments 
 
Screening Part: 
 
Screening Visit (Visit 1) 
At the Screening Visit, the study doctor will check to see if you are eligible to participate in this 
study. After you sign and date this informed consent form and receive a copy, the following 
procedures will be done at the screening visit. If you are not eligible for the study, the study 
doctor will explain the reasons and arrange for the prescribed standard conventional therapy to 
continue. 


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The following procedures will be performed during the “Screening Visit (Visit 1)”: 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This visit will take about 2-3 hours of your time. 
 
Visit 2 
You will not be required to come to the clinic for this visit. If the results from the “Screening 
Visit” procedures are acceptable to the study doctor, the site study staff will call you and ask you 
a few questions on any changes in your medical condition or medications used and confirm your 
willingness to continue the participation in the study. During this call you will be scheduled for 
next visit and study treatment part of the study. If you are not eligible for the study, you will be 
explained the reasons and arranged for the prescribed standard conventional therapy to continue. 
This phone-call will not take more than 20 minutes of your time. 
 
Study Treatment Part: 
 
Baseline Visit (Visit 3: Day 0) 
The Baseline visit (Visit 3) will occur within 21 days after the Screening Visit. 
 
Below procedures will be performed at Visit 3, before you receive any study drug: 
 
 
 
 
 
 
 
 
 
  
 
 
 


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First Study Drug Dose Application 
Your first dose will be applied topically by a licensed medical professional or trained study staff. 
You will be trained on administration techniques, including how thick the cream layer should be 
on your skin, how to measure needed amount and how to record study drug application 
conditions in patient diary given to you. Study drug cream tubes, plastic cards and precision 
balance to weigh the correct amount of assigned study drug will be provided to you and you will 
be instructed to bring back the study drug tubes (even if they are empty) and the precision 
balances at next visit (Visit 4). All other 13 doses will be applied by yourself and/or by a 
caregiver at home. Ensure to use as instructed and to follow directions while using by the study 
staff. 
 
After First Study Drug Application 
Your study doctor will monitor your condition, any possible side effects and the study treatment 
regimen as described below: 
 
 
 
 
 
 
 
 
 
 
  
 
This visit will take about 2-3 hours of your time. 
 


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End of Study Treatment Visit (Visit 4: Day 7) 
At visit 4 after you receive 14 doses in total (1 dose in-clinic and 13 doses at home), the study 
evaluations will continue and your study doctor will monitor your condition, any possible side 
effects and the treatment regimen as described below: 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
 
This visit will take about 2-3 hours of your time. 
 
Follow-Up Part: 
After completion of Visit 4 procedures, all participants will be followed up for 2 weeks to further 
assess safety and efficacy of study treatment. 
 


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Follow-Up Visit (Visit 5: Day 21±2) 
During the follow-up visit, the following assessments will be performed: 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
This visit will take about 1-2 hours of your time. 
 
Withdrawal Visit: 
For participants who withdraw/are discontinued prematurely during study treatment period, 
“Withdrawal visit” assessments will be performed. Visit 4 assessments will be performed as the 
withdrawal visit evaluations. For all withdrawn/discontinued subjects during study treatment 
period, the Follow-up visit (Visit 5) will happen 2 weeks after the withdrawal visit evaluations.  
 
What are the risks of taking part? 
 
This Part 1 (Phase 1) of the study, AMTX100-AD-01, is the first study in which the study drug, 
AMTX-100 CF topical cream, is given to humans. 
 
There are risks to taking part in any research study. AMTX-100 (active ingredient) and AMTX-
100 CF topical cream (drug product) are still undergoing testing and there may be side effects 
that are unknown at this time.  
 
 


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Animal studies have not indicated that AMTX-100 or AMTX-100 CF topical administration 
might be associated with allergic reactions. 
 
Since AMTX-100 (active ingredient) and AMTX-100 CF topical cream (study drug product) 
have not been studied in humans and AMTX-100, active ingredient, is a new class of medicines 
for atopic dermatitis, side effects in humans are not known. You may or may not experience side 
effects of skin irritation observed in the animal study, however, this is unlikely because the skin 
irritation in animal studies was determined to be due to not appropriately washing off the study 
cream administration sites between AMTX-100 CF twice daily applications for 14 days. To 
reduce the risk of skin irritation, bathing the treated areas will be allowed once daily and 
should be done at least every 3 days keeping normal daily hygiene. 
 
You will be monitored carefully during the administration of study drugs and will be watched 
carefully for side effects or any allergic reactions. As with any study drug, there is a risk of 
allergic reaction.  If you have a very serious allergic reaction, you may be at risk of death.  Some 
symptoms of allergic reactions are: 
 
• 
Rash 
• 
Wheezing and difficulty breathing 
• 
Dizziness and fainting 
• 
Swelling around the mouth, throat or eyes 
• 
A fast pulse 
• 
Sweating 
You need to tell your study doctor or study staffs immediately if you experience any side 
effects, any unfavorable signs or symptoms. If any safety concerns arise, the study treatment 
may be stopped.  
 
Some redness, faintness, pain and swelling may happen due to the blood draws. You may 
experience bruising or bleeding at the site where the needle was placed. There is also a slight 
possibility of infection. 
 
If you do not understand what any of these side effects mean, please ask the study doctor or the 
study staff to explain them to you. 
 
It is unknown whether or not AMTX-100 and AMTX-100 CF topical cream will have any effect 
on unborn children or babies. It is unknown if AMTX-100 can pass through breast milk and it is 




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that such injury results from the study treatment or any other procedure carried out in accordance 
with the plan for the study. The sponsor has no plans to compensate you where such injury 
results from any procedure carried out which is not in accordance with the plan for the study. 
Your legal right to claim compensation for injury is not affected or waived in any way.  
 
If you are injured as a direct result of the use of the study drug, Amytrx Therapeutics, Inc will 
pay for medical expenses for the treatment of the injury that are not covered by your medical 
insurance, a government program or any other third party. Medical care will be provided to you 
through the study doctor and/or institution to treat any physical injury incurred as a direct result 
of the use of the study drug. You must agree to cooperate in obtaining any proceeds from 
insurance or other third party coverage that may be available to you with respect to the costs of 
such medical care. No financial or other form of compensation (such as lost wages or 
discomfort) will routinely be available to you for such injuries; however, you will not lose any of 
your legal rights or release the Sponsor, the study doctor, the study staff, or study site from 
liability for mistakes or intentional misconduct by signing and dating this consent document. 
 
You should talk to the study doctor if you have any questions regarding the study treatment 
during the study, if you feel you did not receive the study treatment you expected, or any other 
concerns. The name and phone number of your study doctor is printed on the first page of this 
consent form. 
 
If you experience a side effect or injury that may be related to this study or if you have an 
unscheduled visit for medical care for any reason, please contact the study doctor listed on page 
one of this informed consent. 
 
If you claim to have become sick or injured from participating in this study, Amytrx 
Therapeutics, Inc. may give information that identifies you to its insurance carrier.  This 
information will be used by the insurance carrier solely for the purpose of resolving your claim. 
To pay medical expenses, the sponsor will need to know some information about you like your 
name, date of birth, and Medicare Beneficiary Identifier (MBI). This is because the sponsor has 
to check to see if you receive Medicare and if you do, report the payment it makes to Medicare. 
 
Will my taking part in this study be kept confidential? 
 
If you agree to take part in this study, your identity and medical records will be kept confidential 
and will not be disclosed outside of the hospital/study site/family physician’s office unless 
required by law. Your medical records may be inspected by Amytrx Therapeutics, Inc (the 
company sponsoring the study).  Your records may also be inspected by a company Amytrx 
Therapeutics, Inc has delegated some study management to, Amarex Clinical Research, LLC. 
(Amarex), for purposes of analyzing the study results and monitoring the study. Regulatory 
authorities such as the U.S. Food and Drug Administration (FDA) and Institutional Review 
Boards (IRB) may review study results and participants records to check that the study is being 
conducted correctly. This means that absolute confidentiality cannot be guaranteed.  If the results 
of this study are published or presented at meetings, you will not be identified. 


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What if new information becomes available? 
 
During the course of a research study, new information may become available about your disease 
or the study treatment that is being studied that might change your decision to be in this study. If 
this happens, your study doctor will discuss this with you and whether you want to continue in 
the study. If you decide to withdraw, your study doctor will make arrangements for your 
prescribed standard conventional therapy to continue. If you decide to continue in the study you 
will be asked to sign and date an updated consent form. 
 
Also, on receiving new information your study doctor might consider it to be in your best interest 
to withdraw from the study. The study doctor will explain the reasons and arrange for your 
prescribed standard care to continue. 
 
What will happen to the results of the research study? 
 
Once the study has finished, the information will be analyzed and a clinical study report will be 
written to record the results. This process can take about 6 months. Your study doctor will be 
kept informed of the results from the study, and a paper detailing these results will probably be 
published in an appropriate medical journal. You can also ask the study doctor for the results of 
the study. 
 
Who is organizing and funding the research? 
 
The company sponsoring and funding this research study is Amytrx Therapeutics, Inc. The study 
site and/or your study doctor is receiving financial support from the sponsor for undertaking this 
study. 
 
Voluntary participation / Withdrawal 
 
Your participation in this study is voluntary. You may decide not to participate or may leave the 
study at any time. Your decision will not result in any penalty or loss of benefits to which you 
are entitled. Tell the study doctor if you are thinking about stopping or have decided to stop.  The 
study doctor will tell you how to stop your participation safely.  
 
It is important to tell the study doctor if you are thinking about stopping your participation so 
that your doctor can evaluate any risks from the study drug and discuss what alternative follow-
up care and testing could be most helpful for you. If you withdraw during the study, you will be 
asked to come in for withdrawal visit, followed by safety follow up visit for safety reasons. Even 
if you don’t want to return for follow-up visits and blood tests, we would still like to collect 
information by phone or available medical records about your disease status. 
 
Early Termination: 
Your participation in this study may be stopped at any time by the study doctor, the sponsor 
(Amytrx Therapeutics, Inc.), the FDA, and/or the IRB without your consent for any of the 
following reasons: 


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• 
If it is in your best interest; 
• 
If you do not consent to continue in the study after being told of changes in the research 
that may affect you; 
• 
If you do not follow research directions; 
• 
If you experience any serious side effects to the study drug; 
• 
If lost to follow-up; 
• 
If you are found to be pregnant; 
• 
If the study is stopped early by the Sponsor (Amytrx), the IRB, the independent Data 
Safety Monitoring Committee (DSMC) or any regulatory agencies such as the U.S. Food 
and Drug Administration (FDA); 
• 
Administrative reasons; 
• 
Or any other reason as determined by the study doctor or the study sponsor. 
 
WHOM TO CONTACT ABOUT THIS STUDY 
During the study, if you experience any medical problems, suffer a research-related injury, or 
have questions, concerns or complaints about the study, please contact the Investigator at the 
telephone number listed on the first page of this consent document. If you seek emergency care, 
or hospitalization is required, alert the treating physician that you are participating in this 
research study.  
 
An institutional review board (IRB) is an independent committee established to help protect the 
rights of research subjects. If you have any questions about your rights as a research subject, 
and/or concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Subject Adviser 
Advarra IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Subject Adviser: 
Pro00042081. 
 
 
 


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PRIMARY HEALTH CARE PROVIDER NOTIFICATION OPTION 
 
I consent to having my family doctor or primary health care provider notified by the study site of 
my participation in this study and/or any significant findings related to my health (please check 
yes or no). 
 
 Yes (If yes, please complete the information below) 
 No   
 I do not have a primary care physician/specialist. 
 The study doctor is my primary care physician/specialist. 
 
Name and address of family 
doctor or primary health care 
provider: 
Name: 
Address: 
 
Telephone  
Tel: 
 
 
 
 
 
Do not sign and date this consent form unless you have had a chance to ask questions and have 
received satisfactory answers to all of your questions. 
 
If you agree to be in this study, you will receive a signed and dated copy of this consent form for 
your records. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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PARTICIPANT STATEMENT OF CONSENT 
 
I confirm that I have read this consent form (or it has been read to me) and the content of this 
form has been explained to me. I confirm that I have had the opportunity to ask questions and all 
of my questions were answered to my satisfaction. I agree to participate in this study and comply 
with the requirements to the best of my ability. 
 
My participation in this study is voluntary and I AM free to withdraw at any time, without giving 
any reason, without my medical care or legal rights being affected. 
 
I agree to take part in the above study. 
 
I consent to the use of all anonymized data that is collected from me during this study being 
used, either individually or pooled with other participants, in the analysis of this study, in printed 
publications, or for other purposes as determined by the sponsor, Amytrx Therapeutics, Inc. (The 
word Anonymized means that it will not be possible for you to be identified from the data that is 
collected). 
 
By signing and dating this consent form, I have not given up any of my legal rights. 
 
 
 
 
Printed Name of Participant 
 
 
________________________ 
____________ 
__________ 
Participant’s Signature 
Date 
Time 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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STATEMENT OF PERSON CONDUCTING INFORMED CONSENT DISCUSSION 
AND THE INVESTIGATOR 
 
I, the undersigned, certify that to the best of my knowledge that participant named above had the 
study fully and carefully explained, including the nature, risks, and benefits of his/her 
participation in the research study; and all questions were answered to the study participant’s 
satisfaction. I confirm that the study participant freely and voluntarily gave consent to participate 
in this research study before any study-related procedures were performed. A medical problem or 
language or educational barrier has not precluded this understanding. 
 
I reviewed the consent form with the participant and answered the participant’s questions. The 
participant appeared to have understood the information and was able to answer the following 
questions correctly: 
 
1. What is the purpose of this study? 
2. If you decide to be in the study, what will you be asked to do? 
3. What is the possible benefit of participating in this study? 
4. What are the possible risks of participating in this study? 
5. If you decide not to participate in this study, what options do you have? 
6. Will participating in this study cost you anything? If so, what will you have to pay for? 
7. Do you have to be in this study? 
8. If you decide to be in the study, can you leave the study when you want to? 
 
 
 
 
 
____________ 
__________ 
Signature of Person Conducting 
          Date                      Time 
Informed Consent Discussion 
 
 
 
 
Name of Person Conducting Informed Consent 
Discussion (if different from Study Doctor) 
 
 
I, the undersigned, certify that to the best of my knowledge the study participant named above 
had the study fully and carefully explained, including the nature, risks, and benefits of the 
participant’s participation in the research study. 
 
 
______________________ 
__________ 
__________ 
Signature of Study Doctor 
Date 
Time 
(If different from above) 
 
Original copy to be kept with the researcher; one copy to be given to the subject; one copy 
to be kept with the subject’s medical records. 
 


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Authorization to Use and Disclose Protected Health Information (HIPAA 
Authorization) 
 
While you are participating in this research study, the study doctor and his/her 
study staff will collect and create personal health information about you and record 
it on study forms. This information may include health histories, examinations, and 
results of tests. The study doctor will keep this information in study records. 
He/she may also gather information regarding your past, present, and/or future 
medical conditions from your primary medical doctor. These records may also 
include personal information such as your birth date, social security number, or 
medical record numbers which could be used to identify you. This type of 
information is called “Protected Health Information” (PHI). 
 
Under a United States federal law called the “Privacy Rule” or Health Insurance 
Portability and Accountability Act of 1996 (HIPAA), no one’s PHI that is gathered 
and obtained during research can be used to conduct the research or be given to 
anyone for research purposes without one’s permission. Because of this rule, you 
may not participate in this study unless you give your permission to use and 
disclose your PHI. 
 
By signing and dating this authorization, you are giving permission for the study 
doctor and his/her study staff, along with the Sponsor (Amytrx Therapeutics), 
Amarex Clinical Research (the Contract Research Organization) and the 
Regulatory authorities such as the U.S. Food and Drug Administration (FDA) and 
Institutional Review Boards (IRB) to use your PHI to conduct this study, to 
monitor your health status, and possibly to develop new tests, procedures, and 
commercial products.  
 
You are also agreeing to allow your PHI to be disclosed to the study sponsor and 
any representatives working with them. The sponsor may also give your PHI to the 
FDA or other regulatory agencies. Study staff will assign a code number to you for 
this study. This will help to protect your identity; however, the sponsor may look at 
your complete study records which will identify you. The sponsor will also send 
representatives to your study doctor’s office to oversee how the study is being 
conducted. These representatives will review your PHI to make sure the 
information is correct. The IRB may also have access to your PHI to meet its 
oversight responsibilities. These disclosures help to make sure that all information 
related to the research is available to those who need it. 
 


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Your identity will remain confidential, except for the disclosures described above 
and detailed specifically in the consent page, and will not be shared with others, 
unless it is required by law. If your PHI is given to the parties listed above or to 
anyone who is not required to follow federal law, your PHI will no longer be 
protected by the “Privacy Rule” and could possibly be used or disclosed in ways 
other than those listed here. 
 
You have the right to see and make copies of your PHI. You are agreeing, 
however, not to see or make copies of your PHI until all of the sponsor work has 
been completed. At that time, you may ask to see your records. 
 
Your HIPAA Authorization will expire 50 years from the date you sign it unless 
you revoke (cancel or withdraw) it sooner. You have the right to cancel or 
withdraw this authorization at any time. If you cancel this authorization, your PHI 
will no longer be used for this study, unless it is necessary (based on your earlier 
authorization) to complete analysis (tests) and reports for this research. 
 
To cancel your permission to use PHI, you must send a written notice to your study 
doctor’s office at the address listed on page one stating that you are canceling your 
authorization for them to use or disclose your protected health information. If you 
cancel this authorization, you will not be allowed to continue in this study. 
 
Subjects will receive a signed and date copy of this document. 
 
 
 


Amytrx Therapeutics, Inc./ Protocol Number AMTX100-AD-01  
Page 21 of 21   
  
«PiFullName» 
Advarra IRB Approved Version 27 Feb 2020 
Revised «PIApprovalDate» 
 
AUTHORIZATION 
 
I authorize the use and disclosure of my health information to the parties listed in 
the HIPAA authorization for the purposes described above. 
 
 
___________________________________ 
Printed Name of Participant (Study Subject) 
 
 
________________________ 
____________ __________ 
Participant’s Signature 
Date 
Time 
 
 
____________________________________ 
Printed Name of the Person Obtaining the  
Authorization 
 
 
____________________________________ 
 
__________ 
Signature of the Person Obtaining the  
 
 
Date 
 
Original copy to be kept with the researcher; one copy to be given to the subject; one copy 
to be kept with the subject’s medical records. 
 

Prot_000.pdf: 
Protocol # AMTX100-AD-01 
Final Version 4.0 
Date: 12-Jul-2023 
Confidential 
Page 1 of 124 
A TWO PART, PHASE I/II, MULTI-CENTER, DOUBLE-BLIND, RANDOMIZED, 
VEHICLE-CONTROLLED STUDY OF THE SAFETY AND EFFICACY OF TOPICALLY 
APPLIED AMTX-100 CF IN ADULT PATIENTS WITH MILD TO MODERATE ATOPIC 
DERMATITIS 
Protocol Number:
Version Number: 
Version Date 
Development Phase: 
Investigational Compound: 
Control: 
Sponsor: 
Protocol Prepared By: 
AMTX100-AD-01 (NCT04313400)
Final Version 4.0 
12Jul2023 
Phase I/II 
AMTX-100 CF3 
Vehicle (Placebo) 
Amytrx Therapeutics, Inc. 
Amarex Clinical Research, LLC. 
20201 Century Blvd, 4th floor 
Germantown, MD  20874 USA 
Confidentiality Statement 
This protocol is provided for conducting a clinical research study. The information contained in this 
document is confidential and, except to the extent necessary to obtain informed consent or IEC/IRB 
approval, cannot be disclosed unless required by governmental regulation. Persons to whom any portion 
of the contents of this document is disclosed must be informed that the information is confidential and 
may not be further disclosed by them. 


 
 
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PROTOCOL APPROVAL SIGNATURES 
We, the undersigned, have reviewed this protocol and agree that it contains all relevant information 
required to meet FDA, GCP and all applicable regulatory guidelines and statutes. 
 
 
 
 
 
 
 
 
 
Project Lead 
 
Signature 
 
Date 
 
 
 
 
 
 
 
 
Safety and Pharmacovigilance  
 
Signature 
 
Date 
 
 
 
 
 
 
 
 
Biometrics  
 
Signature 
 
Date 
 
 
 
 
 
 
 
 
Medical Writing  
 
Signature 
 
Date 
 
 
 
 
 
 
Sponsor Representative 
 
Signature 
 
Date 
 
 


 
 
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INVESTIGATOR SIGNATURE PAGE 
I have read the protocol specified above and agree to participate in and comply with the procedures, as 
detailed herein for the conduct of this clinical trial. I also agree to comply with the applicable US Food 
and Drug Administration (FDA) regulations and Institutional Review Board (IRB) requirements for 
testing on human subjects. I agree to ensure that the requirements for obtaining informed consent are 
met.  
 
 
 
 
 
 
 
Principal Investigator’s Signature 
 
 
 
 
 
Date 
Print Name 
 
 
 
 
 
 
 
Site Number 
 
 
 
 
 
 
 
 








































 
 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS................................................................................................................... 5 
PROTOCOL SYNOPSIS ......................................................................................................................... 8 
TABLE OF CONTENTS ....................................................................................................................... 23 
LIST OF TABLES .................................................................................................................................. 26 
LIST OF FIGURES ................................................................................................................................ 27 
1 INTRODUCTION ............................................................................................................................ 28 
1.1 
Statement of Intent ....................................................................................................................... 28 
1.2 
Study Background ........................................................................................................................ 28 
1.3 
AMTX-100 Background and Prior Studies .................................................................................. 29 
1.3.1 
AMTX-100 Pre-clinical studies ................................................................................. 30 
1.4 
Study Design Rationale ................................................................................................................ 31 
1.5 
Risks and Benefits, and Precautions to Minimize Risk ............................................................... 31 
1.5.1 
Allergic Reaction ....................................................................................................... 33 
1.5.2 
Pregnancy ................................................................................................................... 33 
1.5.3 
Venipuncture for blood sampling............................................................................... 33 
1.5.4 
Unknown Risks .......................................................................................................... 33 
1.6 
First-In Human Dose Selection Rationale .................................................................................... 33 
2 STUDY OBJECTIVES .................................................................................................................... 35 
3 STUDY DESIGN ............................................................................................................................. 36 
3.1 
Phase I (Part 1) Study Design ...................................................................................................... 36 
3.2 
Phase I (Part 1) Study Visits ........................................................................................................ 39 
3.3 
Phase II (Part 2) Study Design ..................................................................................................... 42 
3.4 
Phase II (Part 2) Study Visits ....................................................................................................... 43 
3.5 
Study Population .......................................................................................................................... 45 
3.5.1 
Number of Subjects .................................................................................................... 45 
3.5.2 
Subject Sources .......................................................................................................... 45 
3.5.3 
Phase I (Part 1) Inclusion Criteria .............................................................................. 45 
3.5.4 
Phase I (Part 1) Exclusion Criteria ............................................................................. 46 
3.5.5 
Phase II (Part 2) Inclusion Criteria ............................................................................. 47 
3.5.6 
Phase II (Part 2) Exclusion Criteria ........................................................................... 48 
4 STUDY SCHEDULE ....................................................................................................................... 50 
4.1 
Phase I (Part 1) Study Visits ........................................................................................................ 56 
4.1.1 
Phase I (Part 1) - Visit 1: Screening Visit (Up to -21 days) ....................................... 56 
4.1.2 
Phase I (Part 1) - Visit 2 (Up to – 7 Days±2) ............................................................. 56 
4.1.3 
Phase I (Part 1) - Visit 3: Baseline Visit (Day 0) ....................................................... 57 
4.1.4 
Phase I (Part 1) - Visit 4: End of treatment (Week 1: Day 7) .................................... 57 


 
 
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4.1.5 
Phase I (Part 1) - Visit 5: Follow up (Week 3: Day 21±2) ........................................ 58 
4.2 
Phase II (Part 2) Study Visits ....................................................................................................... 58 
4.2.1 
Phase II (Part 2) - Visit 1: Screening Visit (Up to -28 days) ..................................... 58 
4.2.2 
Phase II (Part 2) - Visit 2: Randomization/Baseline Visit (Day 0) ............................ 59 
4.2.3 
Phase II (Part 2) - Visit 3 (Week 1: Day 7±1) ............................................................ 60 
4.2.4 
Phase II (Part 2) - Visit 4 (Week 2: Day 14±1) .......................................................... 61 
4.2.5 
Phase II (Part 2) - Visit 5 (Week 3: Day 21±1) .......................................................... 61 
4.2.6 
Phase II (Part 2) - Visit 6: End of Treatment (Week 4: Day 28±1) ........................... 62 
4.2.7 
Phase II (Part 2) - Visit 7: Follow up (Week 6: Day 42±3) ....................................... 63 
4.3 
Unscheduled Visits ....................................................................................................................... 64 
4.4 
Missed Visits ................................................................................................................................ 64 
5 SUBJECT COMPLETION AND WITHDRAWAL, STUDY EARLY DISCONTINUATION .... 65 
5.1 
Subject Completion ...................................................................................................................... 65 
5.2 
Subject Premature Withdrawal from the Study ........................................................................... 65 
5.3 
Screen Failures ............................................................................................................................. 66 
5.4 
Early Discontinuation of The Clinical Trial ................................................................................. 66 
6 STUDY TREATMENTS.................................................................................................................. 67 
6.1 
Method for Assigning Eligible Subjects to Treatment ................................................................. 67 
6.2 
Study Treatment Description ....................................................................................................... 68 
6.3 
Study Treatment Labeling and Packaging ................................................................................... 69 
6.4 
Study Treatment Storage .............................................................................................................. 71 
6.5 
Study Treatment Administration .................................................................................................. 71 
6.6 
Study Treatment Dispensation ..................................................................................................... 74 
6.7 
Study Treatment Accountability .................................................................................................. 75 
6.8 
Study Treatment Compliance ....................................................................................................... 75 
7 CONCOMITANT AND PROHIBITED MEDICATIONS AND FOODS ...................................... 76 
8 DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES ................................... 79 
8.1 
Informed Consent ......................................................................................................................... 79 
8.2 
Eligibility Assessment .................................................................................................................. 79 
8.3 
Subject Demographics ................................................................................................................. 80 
8.4 
Medical History ............................................................................................................................ 80 
8.5 
Vital Signs .................................................................................................................................... 81 
8.6 
Height, Weight, BMI and BSA .................................................................................................... 82 
8.7 
Physical Exam .............................................................................................................................. 82 
8.8 
Laboratory Assessments ............................................................................................................... 82 
8.9 
Urine Pregnancy Test ................................................................................................................... 84 
8.10 Electrocardiogram (ECG) ............................................................................................................ 84 
8.11 Cohort Assignment (Part 1 only, sequential) ............................................................................... 84 


 
 
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8.12 Randomization (Part 2 only) ........................................................................................................ 85 
 
 
 
 
 
 
 
 
 
 
9 STATISTICAL CONSIDERATIONS ............................................................................................. 99 
9.1 
Treatment Groups ......................................................................................................................... 99 
9.2 
Description of Study Outcome Measures .................................................................................... 99 
9.2.1 
Phase I (Part 1) Study Outcome measures ................................................................. 99 
9.2.2 
Phase II (Part 2) Study Outcome measures .............................................................. 100 
9.3 
Sample Size Determination and Rationale ................................................................................. 102 
9.4 
Randomization ........................................................................................................................... 102 
9.5 
Blinding and Prevention of Bias ................................................................................................ 102 
9.6 
Interim Analysis (IA) ................................................................................................................. 103 
9.7 
General Statistical Considerations ............................................................................................. 103 
9.8 
Analysis Populations .................................................................................................................. 103 
 
 
 
 
 
 
9.9 
Handling of Missing data ........................................................................................................... 104 
9.10 Covariates and Prognostic Factors ............................................................................................. 104 
9.11 Type I error Rate Adjustment .................................................................................................... 104 
9.12 Statistical Methods ..................................................................................................................... 104 
9.12.1 
Subject Disposition .................................................................................................. 104 
9.12.2 
Demographics And Baseline Characteristics Analysis ............................................ 105 
9.12.3 
Concomitant Medications/Therapies ....................................................................... 105 
9.13 Analyses for the outcomes of the Part 1 study ........................................................................... 105 
9.14 Analyses for the outcomes of the Part 2 study ........................................................................... 106 
10 ADVERSE EVENTS (DEFINITIONS AND REPORTING) ........................................................ 107 
10.1 Adverse Events ........................................................................................................................... 107 
10.1.1 
Reporting of Adverse Events ................................................................................... 107 
10.1.2 
Impact on Study Treatment ...................................................................................... 107 






 
 
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1 
INTRODUCTION 
1.1 
STATEMENT OF INTENT 
The design, conduct and reporting of this trial shall be conducted in compliance with the protocol, 
International Conference on Harmonization (ICH)/Good Clinical Practice (GCP) and all appropriate 
regulatory requirements. The protocol will follow 21 Code of Federal Regulations (CFR) 50, subpart D 
and will provide all the necessary safeguards for study subjects. All of the Investigators will have 
documented training in GCP. Independent monitoring of the trial will be accomplished by utilizing a 
Contract Research Organization (CRO). 
1.2 
STUDY BACKGROUND  
Atopic Dermatitis (AD) is a chronic, pruritic inflammatory skin disease of unknown origin that usually 
starts in early infancy, but also affects a substantial number of adults. AD affects 15-30% of children and 
2-10% of adults globally, and its prevalence rate is rising (Alhazmi, 2017). AD onset is most common 
between 3 and 6 months of age, with approximately 60% of patients developing the eruption in the first 
year of life and 90% by 5 years of age (Kay, 1994; Perkin, 2004).  While the majority of affected 
individuals have resolution of disease by adulthood, 10% to 30% do not, and a smaller percentage of 
individuals first develop symptoms as adults (Ellis, 2012).  
AD is often associated with elevated serum immunoglobulin (IgE) levels and a personal or family history 
of type I allergies, allergic rhinitis, and asthma (Eichenfield, 2014). AD typically presents with pruritus, 
xerosis, lichenification, and eczematous lesions. Excoriations and crusting are common and some 
patients exhibit prurigo nodularis‒like lesions. The eczematous changes and its morphology are seen in 
different locations depending on the age of the patient. In adults, lesions are more diffuse with an 
underlying background of erythema. The face is commonly involved and is dry and scaly. The mainstays 
of treatment are moisturization (frequent lukewarm baths, and using petrolatum or Aquaphor, etc.), along 
with topical steroids (Eichenfield, 2014). For more severe cases, other treatment options such as 
immunomodulators (ex. tacrolimus and pimecrolimus), biologicals (ex. dupilumab and omalizumab), 
topical phosphodiesterase-4 (PDE-4) inhibitors (ex. crisaborole), probiotics and phototherapy are also 
used (Sidbury, 2014). All of these options for AD management, and many of these treatment regimens 
are considered expensive and with various side effects in chronic use. Thus, patients with AD are in need 
of new treatment options that are efficacious and safe in the long term use.  
AMTX-100 CF3 drug product is formulated as a water-based, topical cream incorporating a 28-amino 
acid synthetic polypeptide (AMTX-100) as the active pharmaceutical ingredient (API).  
AMTX-100 is a chimeric, cell-penetrating, bifunctional nuclear transport modifier (NTM), that is 
engineered to modulate nuclear transport of transcription factors (NF-κB, NFAT, AP-1 and STAT1) 
involved in activation of gene expression of key mediators of inflammation (TNFα, IL-1β, IL-6, IL-17, 
MCP-1, etc.) and metabolic syndrome (ChREBP and SREBP) by importin α/β complex and importin β, 


 
 
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respectively. This further leads to a reduction in pro-inflammatory cytokine/chemokine production and 
carbohydrate and lipid metabolic products.  
Several nonclinical safety studies have been conducted with AMTX-100 and AMTX-100 CF to evaluate 
its toxicological profile and additional studies are currently ongoing. Substantial scientific literature is 
also available on the anti-inflammatory mechanisms of AMTX-100.  
The current study is designed to evaluate the safety and tolerability of open-label topically applied 
AMTX-100 CF3 (in 1.1% concentration) and to evaluate the safety and efficacy of topically applied 
AMTX-100 CF3 (1.1% w/w) in adult patients with mild to moderate AD. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




 
 
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1.4 
STUDY DESIGN RATIONALE 
Following substantial prior pre-clinical studies, to further evaluate the safety and efficacy of different 
doses of AMTX-100 drug product in improving symptoms associated with mild to moderate atopic 
dermatitis, Amytrx Therapeutics, Inc (Sponsor) plans to conduct this Two-part, Phase I/II, Multi-center, 
Double-Blind, Randomized, Vehicle-controlled Study of the Safety and Efficacy of topically applied 
AMTX-100 CF in adult patients with Mild to Moderate Atopic Dermatitis. 
1.5 
RISKS AND BENEFITS, AND PRECAUTIONS TO MINIMIZE RISK  
To ensure that AMTX-100 (active pharmaceutical ingredient) and AMTX-100 CF (topical 
formulation) are safe as a human therapeutic agent, below safety studies were conducted. All 
toxicology studies of AMTX-100 CF and AMTX-100 are listed in Table 1-1, including information 
on the Good Lab Practices (GLP) status and testing facility.  
 


 
 
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All these study results indicate that AMTX-100 CF topical formulation is safe for clinical application. 
Based on the current data, AMTX-100 may show anti-inflammatory mechanism of action and improve 
symptoms associated with atopic dermatitis. 
1.5.1 ALLERGIC REACTION 
Pre-clinical studies have not shown that AMTX-100 or AMTX-100 CF topical administration might be 
associated with allergic reactions, however in this first in human study sufficient surveillance of any 
adverse events and administration reactions will be conducted.  
1.5.2 PREGNANCY 
Risks to unborn babies are unknown at this time, thus pregnant females will be excluded from this study. 
Females of childbearing potential must have a negative pregnancy test prior to enrollment and must agree 
to use appropriate birth control methods throughout the study duration (excluding women who are not 
of childbearing potential).  
1.5.3 VENIPUNCTURE FOR BLOOD SAMPLING 
Venipuncture for blood sample collection carries a minimal risk of minor discomfort and the possibility 
of minor bruising at the site of the needle puncture and, rarely, the possibility of infection at the needle 
puncture site. 
1.5.4 UNKNOWN RISKS 
As with all research there is the remote possibility of risks that are unknown or that cannot be foreseen 
based on current information.  
 
 
 
 
 


 
 
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2 
STUDY OBJECTIVES 
This is an adaptive, Phase I/II study in 2 parts: Part 1 (Maximum Tolerable Dose (MTD) Finding by 
maximum BSA percentage treated) and Part 2 (evaluating efficacy of AMTX-100 CF3 versus placebo 
(vehicle)). 
Phase I (Part 1) Objectives: 
• The primary objective of Part 1 of this study is to determine the MTD of topically applied 
AMTX-100 CF (in 1.1% w/w concentration) in adult patients with mild to moderate Atopic 
Dermatitis (AD) while escalating the treatable BSA involved in sequential cohorts. 
• The secondary objective of Part 1 of this study is to evaluate the safety, tolerability and efficacy 
of topically applied AMTX-100 CF (in 1.1% w/w concentration) in improving symptoms 
associated with mild to moderate Atopic Dermatitis in adults. 
Phase II (Part 2) Objectives: 
• The primary objective of Part 2 of this study is to evaluate efficacy of AMTX-100 CF3 1.1% 
w/w versus placebo (0 % w/w)(Vehicle). 
• The secondary objective of Part 2 of this study is to evaluate the safety and tolerability of AMTX-
100 CF3 1.1% w/w compared to placebo (0 % w/w). 
 
 
 
 
 
 
 


 
 
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3 
STUDY DESIGN  
This is an adaptive, Phase I/II study in 2 parts: Part 1 (Maximum Tolerable Dose (MTD) Finding by 
maximum BSA percentage treated) and Part 2 (evaluating efficacy of AMTX-100 CF3 1.1% w/w 
concentration versus placebo (vehicle)). 
3.1 
PHASE I (PART 1) STUDY DESIGN 
Part 1 of this study is an open-label, dose escalation study of the safety and tolerability of topically 
applied AMTX-100 CF in adult patients with mild to moderate AD. Part I of this study is designed to 
determine the MTD of AMTX-100 CF (1.1% w/w concentration) for the highest treated percentage of 
the BSA affected with AD. The MTD is defined as 1 cohort dose level below the dose, in which dose 
limiting toxicities (DLTs) as defined below were observed. 
In total, five (5) cohort dose levels will be tested sequentially by escalating AMTX-100 CF 1.1% to 
higher percentage of BSA affected with AD at each cohort. Each enrolled subject will receive the 
assigned dose of Open-label AMTX-100 CF 1.1% w/w to be applied twice daily to all treatable lesions 
of AD (excluding the scalp, face, eyes, eyelids, neck, hands, palms, feet, groin, genitals or in the axillae) 
for 7 consecutive days (14 applications in total), regardless of whether the lesions become clinically clear 
during the 7 days treatment period.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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For schematics of the cohort escalation and design of Phase I (Part 1) of the study, see text Figure 3-1 
and Figure 3-2. 


 
 
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3.2 
PHASE I (PART 1) STUDY VISITS 
 
 
  


 
 
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Assuming no DLTs occur at any cohorts, in Part 2 (Phase II) of the study, 1.1% w/w dose concentration 
of AMTX-100 CF3 will be further evaluated for the safety and efficacy, compared to placebo (vehicle), 
in adult patients with mild to moderate AD, with up to 30% treatable BSA involvement. 
 


 
 
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3.3 
PHASE II (PART 2) STUDY DESIGN 
Phase II (Part 2) of this study is a multi-center, double-blind, randomized, vehicle-controlled study of 
the safety and efficacy of topically applied AMTX-100 CF3 in adult patients with Mild to Moderate AD. 
Sixty (60) subjects will be enrolled in 2 groups of AMTX-100 CF3 and placebo (vehicle). The subjects 
will be randomized in a 1:1 ratio, thus thirty (30) subjects will be randomized in each group (Group A: 
Treatment 1.1% w/w of AMTX-100 CF3) and Group B: placebo (vehicle 0% w/w)). Each enrolled 
subject, after screening and randomization, will receiveAMTX-100 CF3 1.1% w/w or placebo (vehicle) 
to be applied twice daily to all treatable AD lesions (excluding the scalp, face, eyes, eyelids, hands, 
palms, feet, groin, genitals or in the axillae) for 28 consecutive days.  
The study groups are as follows: 
• Group A: AMTX-100 CF3 dose concentration (1.1% w/w), topically applied twice a day for 28 
consecutive days to all treatable AD affected areas  
• Group B: Placebo (Vehicle) (0% w/w), topically applied twice a day for 28 consecutive days to all 
treatable AD affected areas  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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3.4 
PHASE II (PART 2) STUDY VISITS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 


 
 
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3.5 
STUDY POPULATION 
3.5.1 NUMBER OF SUBJECTS 
Phase I (Part 1): Twenty-five (25) subjects will be enrolled in Phase I of the study at up to 5 centers 
within the USA, including hospitals and freestanding/outpatient dermatology or allergy/immunology 
clinics. The sample size of 25 subjects (5 subjects per cohort) for phase I of this study is selected on the 
basis of clinical judgment and not based on statistical power calculation. The number of subjects is 
deemed adequate to provide clinically meaningful descriptive results consistent with study objectives. 
Phase II (Part 2): Sixty (60) subjects will be enrolled in Phase II of the study at up to 20 centers within 
the USA, including hospitals and freestanding/outpatient dermatology or allergy/immunology clinics. 
The sample size of 60 subjects for Phase II of this study is selected on the basis of clinical judgment and 
not based on statistical power calculation. The number of subjects is deemed adequate to provide 
clinically meaningful results consistent with study objectives. 
3.5.2 SUBJECT SOURCES 
Patients referred to and those who are current patients of hospitals and freestanding/outpatient 
dermatology or allergy/immunology clinics for treatment of atopic dermatitis will be eligible for the 
study. 
3.5.3 PHASE I (PART 1) INCLUSION CRITERIA  
Subjects are required to meet ALL of the following criteria for enrollment into the Phase I (Part 1) of the 
study: 
1. Male or female subjects who are 18 years or older 
2. If female and not infertile (defined below), the subject must agree for the duration of the study to use 
one of the following forms of contraception 1) systemic hormonal treatment 2) an intrauterine device 
(IUD) which was implanted at least 2 months prior to screening or 3) "double-barrier" contraception 
(condom, diaphragm and spermicide are each considered a barrier). Females are considered to be 
infertile if they are either a) surgically sterile or b) have had spontaneous amenorrhea for at least the 
last 2 years and at least 2 years after the onset of amenorrhea while not receiving hormone 
replacement therapy and had a Follicle-Stimulating Hormone (FSH) level greater than 40 mIU/mL 
and an estradiol level less than 30 pg/mL 
3. All fertile female subjects as described above need to have a negative urine pregnancy test at the 
screening and baseline visits  
4. Subject is capable of providing informed consent and is willing to sign the ICF prior to study 
Screening and agrees to comply with the study protocol requirements 
5. Subject is able to apply topical products on all treatable assigned areas by self and/or caregiver (if 
applicable), per the Investigator 


 
 
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6. Subject is in general good physical/mental health per the Investigator 
7. Subject’s Total Body Surface Area (BSA) is between 1.5 and 2.1 m2 per the Mosteller formula 
8. The subject has physician confirmed mild to moderate Atopic Dermatitis (AD) defined by the 
Eichenfield revised criteria of Hannifin and Rajka, for at least 6 months prior to study enrollment  
9. Validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD™) score of 2 or 3 
(mild to moderate) at the screening and baseline visits 
10. Subject has Atopic Dermatitis (AD) involvement with eligible treatable percent of the BSA 
appropriate for topical treatment per the assigned cohort at the screening and baseline visits per below: 
f. Cohort 1: 3% BSA ≤ AD Affected Area ≤ 6% BSA 
g. Cohort 2: 6% BSA < AD Affected Area ≤ 12% BSA 
h. Cohort 3: 12% BSA < AD Affected Area ≤ 24% BSA 
i. Cohort 4: 24% BSA < AD Affected Area ≤ 48% BSA 
j. Cohort 5: 48% BSA < AD Affected Area ≤ 70% BSA 
 
 
 
  
 
 
 
 
3.5.4 PHASE I (PART 1) EXCLUSION CRITERIA 
Subjects are required to meet NONE of the following criteria for enrollment into the Phase I (Part 1) of 
the study: 
1. Pregnant or lactating females or women who are planning for pregnancy in the next 6 months 
2. Women at postpartum for 3 months or less prior to screening  
3. Serious medical illnesses such as end-stage renal disease, liver failure or heart failure that, in the 
opinion of the Investigator may interfere with the conduct of the study 
4. Subjects with abnormal vital signs, physical and dermatological exams or clinical laboratory 
evaluations considered clinically significant by the Principal Investigator, which in the opinion of 
the PI would significantly interfere with the study conduct 
5. Subjects with any concurrent skin condition that could interfere with the evaluation of the treatment 
areas, as determined by the investigator 
6. The subject has a planned major surgical intervention for a pre-existing condition within the duration 
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7. The subject has a history of drug or alcohol abuse that would impair or risk the subject’s full 
participation in the study, in the opinion of the investigator. 
8. Participation in a clinical trial within 3 months, or more than two clinical trials within 12 months 
prior to screening 
9. Concurrent or recent use of topical steroids, topical immunosuppressive/immunomodulative drugs, 
topical vitamin D3 derivative, topical retinoids, anthralin, coal tar (except when used as shampoo) 
or salicylic acid within 14 days of the baseline visit 
10. The subject has severe AD as determined by vIGA-AD™ score higher than 3 
11. The subject cannot avoid systemic treatments (including systemic corticosteroids, immunotherapy, 
biologics or phototherapy) for AD during the study per the Investigator 
12. The subject has previously received any systemic treatments, immunotherapy, biologics or 
phototherapy for AD within 12 months prior to study enrollment 
13. Current or expected use of prohibited medications as described in Section 7, unless approved by the 
study Medical Monitor 
14. The subject has concurrent contact dermatitis; or history of anaphylactic reaction 
3.5.5 PHASE II (PART 2) INCLUSION CRITERIA  
Subjects are required to meet ALL of the following criteria for randomization into the Phase II (Part 2) 
of the study: 
1. Male or female subjects who are 18 years or older. 
2. If female and not infertile (defined below), the subject must agree for the duration of the study to use 
one of the following forms of contraception 1) systemic hormonal treatment 2) an intrauterine device 
(IUD) which was implanted at least 2 months prior to screening or 3) "double-barrier" contraception 
(condom, diaphragm and spermicide are each considered a barrier). Females are considered to be 
infertile if they are either a) surgically sterile or b) have had spontaneous amenorrhea for at least the 
last 2 years and at least 2 years after the onset of amenorrhea while not receiving hormone 
replacement therapy.  
3. All fertile female subjects as described above need to have a negative urine pregnancy test at the 
screening and baseline visits. 
4. Subject is capable of providing informed consent and is willing to sign the ICF prior to study 
Screening and agrees to comply with the study protocol requirements. 
5. Subject is able to apply topical products on all the treatable areas by self and/or caregiver (if 
applicable), per the Investigator. 
6. Subject is willing and able to comply with all clinic visits and study-related procedures. 
7. Subject is able to understand and complete study-related questionnaires. 


 
 
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8. The subject has physician confirmed mild to moderate Atopic Dermatitis (AD) defined by the 
Eichenfield revised criteria of Hannifin and Rajka, for at least 6 months prior to study enrollment.  
9. Validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD™) score of 2 or 3 
(mild to moderate) at the screening and baseline visits. 
10. Eczema Area and Severity Index (EASI) score lower than 23 at the screening and baseline visits 
11. Subject has Atopic Dermatitis (AD) involvement between 5% and 30% treatable BSA (excluding 
the scalp, face, eyes, eyelids, hands, palms, feet, groin, genitals or in the axillae) appropriate for 
topical treatment at the screening and baseline visits. 
Note: Calculation of Treatable BSA percentage (% of the total BSA that is AD-involved, excluding 
the scalp, face, eyes, eyelids, hands, palms, feet, groin, genitals or in the axillae) will be completed 
by Rule of Nines method: 
o  Where values of 9% or 18% of BSA are assigned to specific regions in the adult subject 
(head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs 
[36%], and genitals [1%]) 
12. Subjects must be applying an additive-free, basic, bland emollient twice-daily for at least 1 week 
immediately before the baseline visit (Visit 2, Day 0), and to be continued throughout the study.  
Note: The additive-free, basic, bland emollients should be applied no earlier than 1 hour before or 
1 hour after the administration of the study treatment. 
3.5.6 PHASE II (PART 2) EXCLUSION CRITERIA 
Subjects are required to meet NONE of the following criteria for randomization into the Phase II (Part 
2) of the study: 
1. Pregnant or lactating females or women who are planning for pregnancy in the next 6 months 
2. Women at postpartum for 3 months or less prior to screening  
3. Serious medical illnesses such as end-stage renal disease, liver failure or heart failure that, in the 
opinion of the Investigator may interfere with the conduct of the study 
4. Subjects with abnormal vital signs, physical and dermatological exams or clinical laboratory 
evaluations considered clinically significant by the Principal Investigator, which in the opinion of 
the PI would significantly interfere with the study conduct 
5. Subjects with any concurrent skin condition that could interfere with the evaluation of the treatment 
areas, as determined by the investigator 
6. The subject has a planned major surgical intervention for a pre-existing condition within the duration 
of the study 
7. The subject has a history of drug or alcohol abuse that would impair or risk the subject’s full 
participation in the study, in the opinion of the investigator. 


 
 
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8. Participation in a clinical trial within 3 months, or more than two clinical trials within 12 months 
prior to screening 
9. Concurrent 
or 
recent 
use 
of 
prescription 
moisturizers, 
topical 
steroids, 
topical 
immunosuppressive/immunomodulative drugs, topical vitamin D3 derivative, topical retinoids, 
anthralin, coal tar (except when used as shampoo) or salicylic acid within 14 days of the baseline 
visit 
10. The subject has severe AD as determined by vIGA-AD™ score higher than 3 
11. The subject cannot avoid systemic treatments (including systemic corticosteroids, immunotherapy, 
biologics or phototherapy) for AD during the study per the Investigator 
12. The subject has previously received any systemic treatments, immunotherapy, biologics or 
phototherapy for AD within 12 months prior to study enrollment 
13. Current or expected use of prohibited medications and procedures during study treatment, as 
described in Section 7, unless approved by the study Medical Monitor 
14. Subject has unstable AD or any consistent requirement for high-potency topical corticosteroids to 
manage AD signs and symptoms 
15. Subject has a significant active systemic or localized infection, including known actively infected 
AD 
16. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening 
visit 
17. The subject has previously received AMTX-100 CF 
18. Subject has any other medical or psychological condition (including relevant laboratory 
abnormalities at screening) that, in the opinion of the investigator, may suggest a new and/or 
insufficiently understood disease, may present an unreasonable risk to the study patient as a result of 
his/her participation in this clinical trial, may make patient’s participation unreliable, or may interfere 
with study assessments. 
19. The subject has concurrent contact dermatitis; or history of anaphylactic reaction. 
 
 


 
 
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4 
STUDY SCHEDULE 
The schedules for the protocol-specified assessments and procedures for Phase I (Part 1) and Phase II 
(Part 2) of this study are detailed in this section. Day 0 is used as the day of baseline/randomization and 
first study treatment administration in both parts of the study. See Table 4-1: 
Phase I (Part 1) - 
Study Schedule of Events and Table 4-2: 
Phase II (Part 2) - Study Schedule of Events. 
 












 
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4.1 
PHASE I (PART 1) STUDY VISITS 
4.1.1 PHASE I (PART 1) - VISIT 1: SCREENING VISIT (UP TO -21 DAYS) 
The subject will sign and date the ICF, and Health Insurance Portability and Accountability Act (HIPAA) 
authorization (according to site practices) prior to any study-related procedures. A subject number will 
be assigned to each subject in successive order of consent signing at each center, beginning with 001 at 
each site. Each study site will receive a unique numeric designation, and will precede the subject number 
(e.g. at study center 01 the first two consented subjects would be 01-001 and 01-002; at study center 02 
the first two consented subjects would be 02-001 and 02-002).  
Screening Visit procedures of Phase I (Part 1) of the study are per below: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.1.2 PHASE I (PART 1) - VISIT 2 (UP TO – 7 DAYS±2) 
If continued to be eligible for the study at Visit 2, the subject will proceed to be enrolled into Phase I 
(Part 1) of the study. All entrance criteria must be met; and continued study participation should be 
confirmed via telephone call with the subject by study coordinator or designee, prior to study treatment 
shipment request. The following assessment will be performed: 
 
 
 
 


 
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4.1.3 PHASE I (PART 1) - VISIT 3: BASELINE VISIT (DAY 0) 
The following assessments will be performed: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.1.4 PHASE I (PART 1) - VISIT 4: END OF TREATMENT (WEEK 1: DAY 7)  
The following assessments will be performed: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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4.1.5 PHASE I (PART 1) - VISIT 5: FOLLOW UP (WEEK 3: DAY 21±2)  
After completion of Visit 4 procedures, subject will be followed up 14 days to assess safety and 
tolerability of topically applied AMTX-100 CF. The following assessments will be performed: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.2 
PHASE II (PART 2) STUDY VISITS 
4.2.1 PHASE II (PART 2) - VISIT 1: SCREENING VISIT (UP TO -28 DAYS) 
The subject will sign and date the ICF, and Health Insurance Portability and Accountability Act (HIPAA) 
authorization (according to site practices) prior to any study-related procedures. A subject number will 
be assigned to each subject in successive order of consent signing at each center, beginning with 01 at 
each site. Each study site will receive a unique numeric designation, and will precede the subject number 
(e.g. at study center 01 the first two consented subjects would be 01-001 and 01-002; at study center 02 
the first two consented subjects would be 02-001 and 02-002).  
Screening Visit procedures of Phase II (Part 2) of the study are per below: 
 
 
 
 
 
 
 
 
 


 
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4.2.2 PHASE II (PART 2) - VISIT 2: RANDOMIZATION/BASELINE VISIT (DAY 0) 
If continued to be eligible for the study at Visit 2, the subject will proceed to be randomized into Phase 
II (Part 2) of the study. All entrance criteria must be met prior to randomization of a subject into the 
protocol. The following assessments will be performed: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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4.2.3 PHASE II (PART 2) - VISIT 3 (WEEK 1: DAY 7±1)  
The following assessments will be performed: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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4.2.4 PHASE II (PART 2) - VISIT 4 (WEEK 2: DAY 14±1)  
The following assessments will be performed: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.2.5 PHASE II (PART 2) - VISIT 5 (WEEK 3: DAY 21±1)  
The following assessments will be performed: 


 
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4.2.6 PHASE II (PART 2) - VISIT 6: END OF TREATMENT (WEEK 4: DAY 28±1)  
The following assessments will be performed: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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4.2.7 PHASE II (PART 2) - VISIT 7: FOLLOW UP (WEEK 6: DAY 42±3)  
After completion of Visit 6 procedures, subject will be followed up 14 days to assess safety and 
tolerability of topically applied AMTX-100 CF3. The following assessments will be performed: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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4.3 
UNSCHEDULED VISITS 
Unscheduled visits may be required in addition to the scheduled visits per the Investigator’s discretion. 
The details of these unscheduled visits with subjects will be recorded in the medical records and on the 
electronic Case Report Form (eCRF). 
4.4 
MISSED VISITS 
If a subject misses a visit, the site is to make every effort to have the subject return as soon as possible 
to make up the visit. Once the subject is seen, he/she is to return to his/her original visit schedule.  
 
 


 
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5 
SUBJECT COMPLETION AND WITHDRAWAL, STUDY EARLY DISCONTINUATION  
5.1 
SUBJECT COMPLETION 
 
  
 
 
5.2 
SUBJECT PREMATURE WITHDRAWAL FROM THE STUDY 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
Reasons for subject withdrawal/discontinuation may constitute one of the following: 
 Subject chooses to withdraw  
 Subject is withdrawn due to an AE 
 Pregnancy or positive pregnancy test 
 Lost to follow-up  
 The Investigator determines that it is in the subject’s best interest 
 Excessive protocol deviations, as determined by the Investigator or the Sponsor 


 
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 Discontinuation of the study by the Sponsor 
 
 
 
 
 
 
 
 
 
 
Important Notes: 
1. Subjects may drop out or be withdrawn at their own request. Although subjects do not need to give 
a reason for requesting withdrawal from the trial, the Investigator should make a reasonable effort to 
ascertain the reason(s), while fully respecting the subject's rights. 
2. Any subjects reporting Serious Adverse Events (SAEs) that have not been resolved by their last study 
visit will be followed to resolution or until 30 days after the subject completes the study. 
3. Every attempt should be made to collect follow-up information. The reason for withdrawal from the 
study (if known) will be recorded in the source documents and on the appropriate page of the eCRF. 
4. Before a subject is identified as lost-to-follow-up, the site should make all reasonable efforts to 
contact the subject. These attempts must be documented and should include at a minimum one phone 
call and one follow-up letter.  
5.3 
SCREEN FAILURES 
A subject who has signed the consent form but is not randomized is classified as a screen failure. The 
screen failure must be entered into the study eCRFs. Subject number, demographic information, and 
reason for screen failure will be collected. If a subject initially fails to meet inclusion/exclusion criteria 
and is later reconsidered for participation, the subject can be re-consented only once more, at least 30 
days after the initial screening. The subject will need to be re-consented in such a case and will be 
assigned a new screening number at the time of re-screening.  
5.4 
EARLY DISCONTINUATION OF THE CLINICAL TRIAL 
 
 
 
 


 
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6 
STUDY TREATMENTS 
6.1 
METHOD FOR ASSIGNING ELIGIBLE SUBJECTS TO TREATMENT 
In Part 1 of the study, study eligible subjects will be assigned to open-label AMTX-100 CF (in 1.1% 
concentration), based on a cohort assignment schedule prepared by the contracted CRO. Details of the 
cohort assignment and assignment of the subject number are provided in Section 8.11 and Section 4.1.1. 
Subjects in Part 1 of the study will be assigned sequentially to one of the following treatment groups: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
After a subject has been determined to be eligible for the treatment in Part 1 of the study, a cohort 
assignment number will be assigned. Once the cohort assignment number is assigned, it cannot be re-
assigned even if the subject is subsequently deemed ineligible or withdraws consent.  
 
 
 
  
 


 
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In Part 2 of the study, study eligible subjects will be randomized based on a randomization schedule 
prepared by the contracted CRO. Details of the randomization and assignment of the subject number are 
provided in Section 8.12 and Section 4.2.1. 
Subjects will be randomized in a 1:1 ratio to one of the following treatment groups in Part 2 of the study: 
 Active Treatment (Group A): AMTX-100 CF3 (1.1% w/w);  
 Placebo (Group B): Vehicle ( 0% w/w) 
After a subject has been determined to be eligible for the treatment in the study, a randomization number 
will be assigned. Once the randomization number is assigned, it cannot be re-assigned even if the subject 
is subsequently deemed ineligible or withdraws consent.  
 
 
 
  
6.2 
STUDY TREATMENT DESCRIPTION  
Test treatment for this trial is AMTX-100 CF3. AMTX-100 CF3 is a water-based, white topical cream 
that will be administered to the AD-affected area twice daily for 7 days (total 14 applications) during 
Part 1 of this study and for 28 days (total 56 applications) during Part 2 of this study. 
AMTX-100 CF3 formulation dose per area of skin is 0.002575 g/cm2 in humans. 
AMTX-100 CF3 formulation will be provided in 1.1% w/w concentration. 
The ingredients in each are included in Table 6-1 below. Inactive ingredients used in the manufacturing 
of the drug product are of pharmacopeial quality. 
 


 
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6.3 
STUDY TREATMENT LABELING AND PACKAGING  
Study treatment tubes and cartons will be provided under appropriate investigational product labeling.  
 
 
 
 
 
 
 
  
 
 
 
 
  
  
 
 


 
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6.4 
STUDY TREATMENT STORAGE 
 
 
 
 
 
 
  
6.5 
STUDY TREATMENT ADMINISTRATION   
Detailed guidelines for dose of formulation, administration technique and administration direction can 
be found in the study pharmacy manual.  
In Phase I (Part 1) of study, application areas will be all treatable areas, excluding the scalp, face, eyes, 
eyelids, neck, hands, palms, feet, groin, genitals or in the axillae. The applied amount of AMTX-100 CF 
formulation to the affected assigned areas will depend on the percentage of the BSA affected with AD, 
as assessed by the investigator, and per the formulation dosing tables in the protocol (refer to Table 6-3).  
 
 
 
 
 
 






 
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6.6 
STUDY TREATMENT DISPENSATION 
In Part 1 of the study, subjects will be assigned in the designated cohort (dose level) at the time of 
screening, using an Interactive Web Response System (IWRS) and each subject enrolled into the study 
will receive assigned number of study treatment tubes with specific tube serial number via IWRS, per 
the study cohort assignment scheme and Part 1 study treatment assignment chart (Refer to Table 6-2 and 
Table 6-3). Site study coordinator or designated site personnel will dispense assigned study treatment 
tubes to subject in a carton. The subject will receive sufficient instructions on study drug administration 
compliance and accountability per the above sections. 
In Part 2 of the study, subjects will be randomized using a web-based randomization system (IWRS)  
and each subject enrolled into the study will receive assigned number of study treatment tubes with 
specific tube serial number via IWRS per the study randomization scheme and Part 2 Dosing Chart  (refer 


 
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to Table 6-4). The subject will receive sufficient instructions on study drug administration compliance 
and accountability per the above sections. 
6.7 
STUDY TREATMENT ACCOUNTABILITY 
Study treatments must be used in accordance with this protocol and only under the direction of the 
responsible investigator. The investigational site must maintain complete and accurate records showing 
receipt and disposition of all study treatments, including master records listing the date of receipt, the 
number of the kits received, and a dispensing record which includes each quantity dispensed, 
identification of the staff member to whom dispensed, the date of dispensing, the intended study 
participant subject number, and the identification of the preparer. All used and unused study kits will be 
retained by the investigational site until study treatment accountability can be confirmed by study CRA 
during the monitoring visits. Instructions will be provided by Sponsor regarding final disposition of all 
study drug in compliance with applicable regulations. 
A study treatment accountability log will be provided to the site for use by the Investigator to maintain 
current and accurate inventory records (batch, expiry, and quantity) covering the receipt, dispensing and 
the return/destruction of all the study treatments.  
At the conclusion of the study, the Investigator must agree to return or destroy all study materials as 
instructed by the Sponsor.  
6.8 
STUDY TREATMENT COMPLIANCE 
 
 
 
 
 
 
 
  
 
 


 
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7 
CONCOMITANT AND PROHIBITED MEDICATIONS AND FOODS 
Subjects must be questioned at each study visit concerning any new medications or changes in current 
medications including over-the-counter medication and topical medication.  
All medications and therapies administered or taken by the subject will be recorded in the source 
documents and on the appropriate page of the eCRF per below: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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For each medication and non-study treatment, the following will be documented: 
 Medication/treatment name (generic name may be used if trade name is unknown) 
 Dose, unit, and frequency of dosing (individual dosages, not total daily dose). Note: Each new dose 
of medication should be recorded as a separate entry, with the exception of medications that are given 
on a sliding scale. For these, it is acceptable to enter the range of the dosage, including the start and 
stop dates for which the specified dosage range was used. 
 Route of dosing 
 Indication for use 
 The start date  
 The stop date (if medication/therapy is not ongoing) 
During the study, the subjects will not have any food restrictions, unless food items known to the 
subject/Investigator to trigger AD symptoms. 
 
 


 
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8 
DESCRIPTION OF PROTOCOL ASSESSMENTS AND PROCEDURES 
8.1 
INFORMED CONSENT 
Written informed consent will be obtained for this study by the Investigator or suitably qualified designee 
from all subjects before the performance of any protocol-specific procedure. This study will be 
conducted in accordance with the provisions of the Declaration of Helsinki.  
In obtaining and documenting informed consent, the Investigator must comply with applicable 
regulatory requirements and must adhere to GCP. The Investigator, or designee, must fully inform 
subjects of all pertinent aspects of the study. Before informed consent may be obtained, the Investigator, 
or a person designated by the Investigator, must provide the subject ample time and opportunity to 
inquire about details of the study and to decide whether or not to participate in the trial. All questions 
about the trial must be answered to the satisfaction of the subject. Prior to the subject’s participation in 
the trial, the written informed consent must be signed and personally dated by the subject and by the 
person who conducted the informed consent discussion.  
8.2 
ELIGIBILITY ASSESSMENT 
The eligibility assessment will be done as per inclusion and exclusion criteria of this Protocol as 
described in Sections 3.5.3 and 3.5.4 for Phase I (Part 1) of the study and in Sections 3.5.5 and 3.5.6 for 
Phase II (Part 2) of the study. Diagnosis of atopic dermatitis (AD) will be based on subjects’ medical 
history and records, and confirmed by the Investigator through physical exam, per the Eichenfield 
revised criteria of Hannifin and Rajka (Eichenfield, 2014) (refer to text Table 8-1), and through Validated 
Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD™).  
 


 
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8.3 
SUBJECT DEMOGRAPHICS  
For the purposes of this study, demographic information will include: 
 Date of birth 
 Gender 
 Race (American Indian/Alaskan Native, Asian, Black/African American, Native Hawaiian/Pacific 
Islander, Caucasian, or other) 
 Ethnicity (Hispanic/Latino or Not Hispanic/Latino) 
8.4 
MEDICAL HISTORY 
All ongoing and any prior medical conditions that have resolved in the past year will be recorded at the 
Screening Visit (Visit 1). 
Events that are reported prior to the first study treatment administration will be recorded as part of the 
medical history and not as AEs. Aside from being used to determine subject eligibility, this information 
will permit the Investigator to record the nature, duration and severity of any ongoing baseline medical 
conditions prior to receiving study treatment.  
Medical histories will be recorded using the body system categories outlined below: 


 
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 Cardiovascular  
 Lymphatic  
 Respiratory  
 Hematologic  
 Gastrointestinal  
 Immunologic  
 Renal  
 Dermatologic  
 Hepatic  
 Psychiatric  
 Neurological  
 Genitourinary  
 Endocrine  
 Other 
For each relevant history, the following will be documented:  
 Disease/disorder/condition 
 Date of onset/diagnosis 
 History status (resolved or ongoing) 
 Date of resolution, if applicable 
Subject’s history of AD will be recorded in the Screening eCRF in more details per below: 
 Age of onset 
 Age of diagnosis 
 Treatable % Total Body Surface Area (BSA) with active AD (Refer to Section 8.13) 
 Treatments or procedures received for AD: 
o Within 
90 
days 
prior 
to 
Screening 
for 
topical 
steroids, 
topical 
immunosuppressive/immunomodulative drugs, topical vitamin D3 derivative, topical 
retinoids, anthralin, coal tar (except when used as shampoo) or salicylic acid 
o Within 12 months prior to Screening for systemic treatments, immunotherapy, biologics or 
phototherapy 
8.5 
VITAL SIGNS 
The following vital signs will be collected in the CRF and should be in the subject’s medical records:  
 
 Blood Pressure (systolic and diastolic)* 
 Heart Rate (HR) 
 Respiration Rate (RR) 
 Temperature 
*Note: Blood Pressure will be assessed in “Sitting Position” after 5 minutes’ rest. 


 
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8.6 
HEIGHT, WEIGHT, BMI AND BSA 
Measurements will be taken in street clothing with jacket/coat and shoes removed. Body Mass Index 
(BMI) will be calculated from the height and weight measurements using the following formulas: 
 
• Metric: BMI = Weight (kg) / [Height (m)]2 
Or, 
• Imperial: BMI= Weight (lb) / [Height (in)]2 x 703 
 
Total Body Surface Area (BSA) will be calculated from the height and weight measurements using the 
following Mosteller formula (part 1 only): 
 
• BSA(m2) = ටHeight (cm) x Weight (kg)
3600
 
8.7 
PHYSICAL EXAM 
The physical examination will include routine examinations, including dermatologic examination, but 
not including rectal or genitourinary examinations. All clinically significant abnormalities will be 
recorded in subject’s medical record and on the physical exam CRF page. Any abnormality that, in the 
opinion of the Investigator, is relevant to the safety of the subject or could impact safety or efficacy 
results for the subject will be considered as “clinically significant”. After administration of the first dose 
of study treatment, each physical exam abnormality that is clinically significant will be recorded as an 
AE. 
8.8 
LABORATORY ASSESSMENTS 
The following lab measurements will be obtained (as part of the subject’s medical record) and recorded 
per the study schedule of events: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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•
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.9 
URINE PREGNANCY TEST 
Urine pregnancy test will be performed for females of child-bearing potential. The result must be 
documented on the source documents and in the eCRF. Subjects who are found to be pregnant during 
the screening period will be considered a screen failure. If pregnancy occurs during the course of the 
study, the subject will be withdrawn from the study and the pregnancy will be followed up to term for 
safety purposes. Relevant safety information collected after the study has completed will be reported as 
supplemental information. 
8.10 ELECTROCARDIOGRAM (ECG) 
A standard 12-lead ECG will be performed per the site standard procedures. The following parameters 
will be recorded (as part of the subject’s medical record) and recorded on the appropriate page of the 
CRF: ventricular rate (beats per minute), PR interval (msec), QRS interval (msec), QT interval (msec), 
and QTc interval (msec). Additionally, the Investigator will record the overall results of the ECG reading 
as either normal or abnormal, and if abnormal, as either “not clinically significant” or “clinically 
significant.” If abnormalities are observed, each will be recorded. Each treatment-emergent abnormality 
that is clinically significant will be recorded as an AE. Each ECG should be signed by a physician. 
8.11 COHORT ASSIGNMENT (PART 1 ONLY, SEQUENTIAL) 
In Phase I (Part 1) of the study, five (5) cohort dose levels will be tested sequentially by escalating 
AMTX-100 CF 1.1% application of treatable % BSA involvement at each cohort. Five (5) cohorts will 
be sequentially enrolled in the Part 1 of the study.  
Site personnel will be notified about the cohort (dose level) escalation to the higher dose level cohort. 
Subjects will be assigned in the designated cohort (dose level) at the time of screening, using an 
Interactive Web Response System (IWRS) and site personnel will be trained on this system.   


 
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8.12 RANDOMIZATION (PART 2 ONLY) 
In Phase II (Part 2) of the study, subjects will be randomized using a web-based randomization system 
at Visit 2 and site personnel will be trained on this system.  
 
 
 
 
  
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 


 
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9.2.1.1 Primary Outcome Measure: 
• Maximum Tolerable Dose (MTD) by maximum percentage of BSA treated, by evaluation of 
dose-limiting toxicity (DLT) of AMTX-100 CF (1.1% w/w concentration) based on the safety 
profile  
9.2.1.2 Safety Outcome Measures: 
• Incidence of Treatment-Emergent Adverse Events (TEAE) 
• Incidence of withdrawals from the study due to TEAEs 
• Changes in study treatment application site reaction assessment 
• Changes and shifts in laboratory measurements over time 
• Changes in vital signs over time treatment  
 
 
 
 
9.2.2 PHASE II (PART 2) STUDY OUTCOME MEASURES 
9.2.2.1 Primary Efficacy Outcome Measure: 
• Proportion of responder subjects at Day 28, defined as subjects with both Validated Investigator 
Global Assessment for Atopic Dermatitis (vIGA-AD™) score of 0 (clear) or 1 (almost clear) (on 
a 5-point scale) and a reduction of ≥ 2 points from baseline 
Note: Subjects who receive rescue treatments will be considered non-responders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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9.2.2.4 Safety Outcome Measures 
• Incidence of Treatment-Emergent Adverse Events (TEAE) 
• Incidence of withdrawals from the study due to TEAEs 
• Changes from baseline in study treatment application site reaction assessment 
• Changes and shifts in laboratory measurements over time 
• Changes in vital signs over time 
9.3 
SAMPLE SIZE DETERMINATION AND RATIONALE 
Sample size for Phase I (Part 1): The sample size of 25 subjects (5 subjects per cohort) for Phase I of 
this study is selected on the basis of clinical judgment and not based on statistical power calculation. The 
number of subjects is deemed adequate to provide clinically meaningful descriptive results consistent 
with study objectives.  
Sample size for Phase II (Part 2): The sample size of 60 subjects for Phase II of this study is selected 
on the basis of clinical judgment and not based on statistical power calculation. The number of subjects 
is deemed adequate to provide clinically meaningful results consistent with study objectives. 
9.4 
RANDOMIZATION 
There is no randomization for the Phase I (Part 1) of the study. In Phase II (Part 2) of the study, subjects 
will be randomized using a web-based randomization system at Visit 2 and site personnel will be trained 
on this system. Only those subjects who successfully complete the screening phase and meet the study 
eligibility criteria will proceed to randomization. The randomized subjects will receive study treatment 
at the assigned doses for 28 consecutive days (56 applications in total) and followed up for 2 weeks to 
assess post-treatment safety. 
9.5 
BLINDING AND PREVENTION OF BIAS 
There is no blinding for the Part 1 of the study. However, all subjects, Investigators and their staff, and 
all Sponsor/CRO personnel involved in the management of the study will be blinded to treatment 
assignments for the Part 2 of the study. Treatment unblinding for the study will occur after all clinical 
data have been received, data inconsistencies have been resolved, and the database is locked, except for 
the interim analysis or for safety reasons on a case-by-case basis (i.e., emergency unblinding).  


 
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9.6 
INTERIM ANALYSIS (IA) 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
  
 
 
 
  
 
 
 
 
 
 
9.7 
GENERAL STATISTICAL CONSIDERATIONS  
All collected study data will be presented in subject data listings. Statistical analyses will be performed 
using SAS® for Windows, version 9.4 or later. Descriptive statistics (n, mean, standard deviation, 
median, minimum and maximum) will be calculated for continuous variables. Frequencies and 
percentages will be presented for categorical variables. 
9.8 
ANALYSIS POPULATIONS  
The details of the analysis populations to be used for the study are described in the below sections.   
  
 
 
 


 
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9.9 
HANDLING OF MISSING DATA  
All efforts will be made to avoid missing data; however, there will be no imputation of missing data for 
this early phase study and all summaries will be based on observed data only. 
 
 
 
 
  
9.11 TYPE I ERROR RATE ADJUSTMENT  
This is an early phase study and there is no need for adjustment of Type I error rate.  
9.12 STATISTICAL METHODS  
A Statistical Analysis Plan (SAP) will be developed and approved before the database is locked. The 
SAP will present the detailed statistical methodology to be used in analyzing the efficacy and safety data 
from this trial. 
 
 
  
 
  
 
 
  
 
  
 
 
 
  
 
 
9.12.1   SUBJECT DISPOSITION  


 
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The disposition of all subjects who sign an ICF will be provided. The numbers of subjects screened, 
enrolled/randomized, completed, and discontinued from the study, as well as the reasons for all 
discontinuations will be summarized for each part of the study. Disposition and reason for study 
discontinuation will also be provided as a by-subject listing.   
9.12.2   DEMOGRAPHICS AND BASELINE CHARACTERISTICS ANALYSIS  
Demographics and baseline characteristics will be summarized for each part of the study using 
appropriate descriptive statistics. 
9.12.3   CONCOMITANT MEDICATIONS/THERAPIES 
Concomitant medications will be summarized for each part of the study. All prior and concomitant 
medications recorded in the case report form will be coded to all matching Anatomic Therapeutic 
Classification codes using the most recent version of the WHO Drug Dictionary. Descriptive summaries 
will be prepared using the coded term. In addition, all concomitant medications recorded in the case 
report form will be listed.  
9.13 ANALYSES FOR THE OUTCOMES OF THE PART 1 STUDY 
The primary outcome measure of the Part 1 study is Maximum Tolerable Dose (MTD) by maximum 
percentage of BSA treated, by evaluation of dose-limiting toxicity (DLT) of AMTX-100 CF (1.1% w/w 
concentration) based on the safety profile.  
AEs will be classified by system organ class (SOC) and preferred term (PT) according to the most recent 
version of MedDRA dictionary. All AEs that met the dose escalation stopping criteria will be 
summarized using MedDRA SOC & PT and by relationship to the study treatment for the safety 
population. 
 
 
 
 
 
 
 
 
 
 
 
   
 
  
   


 
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9.14 ANALYSES FOR THE OUTCOMES OF THE PART 2 STUDY 
Efficacy Summaries  
The efficacy evaluable population will be the primary analysis population for the analysis of the efficacy 
outcome measures of the Part 2 study. All the primary and secondary outcome measures will be analyzed 
according to the variable type:  
 
  
 
 
  
 
 
 
 
  
 
  
 
 
 
  
 
  
 
 
  
Safety Summaries  
Similar to the Part 1 of the study, AEs will be coded using MedDRA. Treatment Emergent AE’s (TEAE) 
are defined as events with an onset on or after the first randomized treatment. TEAEs will be summarized 
by treatment groups, system organ class, and preferred term. The following TEAE summaries will be 
provided: 
 
 
 
 
 
 
 
 
 


 
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10 ADVERSE EVENTS (DEFINITIONS AND REPORTING) 
The Investigator is responsible for the detection and documentation of events meeting the criteria and 
definition of an AE or SAE, as provided in this protocol. During the study when there is a safety 
evaluation, the Investigator or site staff will be responsible for detecting, documenting, and reporting 
AEs and SAEs as detailed in this section of the protocol.  
10.1 ADVERSE EVENTS 
An adverse event (AE) is defined as any unfavorable or unintended sign, symptom, or disease that occurs 
or is reported by the subject to have occurred, or a worsening of a pre-existing condition. An AE may or 
may not be related to the study treatment.  
AEs will be elicited through direct questioning and subject reports. Any abnormalities in visit 
evaluations, physical examination findings or laboratory results that the Investigator believes are 
clinically significant to the research subject and that occurred after initiation of the first study treatment 
will be reported as AEs. Abnormal findings that are NOT clinically significant should not be recorded 
as an AE. 
10.1.1 REPORTING OF ADVERSE EVENTS 
Report initiation for all AEs and SAEs will begin at the time of the first study treatment administration 
and continue up until the final study visit. All events will be followed to resolution or until they are 
considered as non-clinically significant event. 
All AEs must be recorded in the subject’s medical records and on the CRF. AEs will be reported using 
customary medical terminology along with the following information: the onset and end dates, whether 
the event is considered to be an SAE (see Section 10.2), the impact the event had on study treatment (see 
Section 10.1.2), the CTCAE grade (intensity) of the event (see Section 10.1.3), the causality of the event 
(see Section 10.1.4), whether treatment was given as a result of the event (see Section 10.1.5), and the 
outcome of the event (see Section 10.1.6). 
10.1.2 IMPACT ON STUDY TREATMENT 
The impact the event had on the study treatment will be assessed as either: none, study treatment 
interrupted, study treatment discontinued, or not applicable. The “not applicable” assessment will be 
used only when the subject is no longer in the treatment phase of the protocol, or if the outcome of the 
event was “death”. 
10.1.3  SEVERITY (INTENSITY) ASSESSMENT 
The guidelines outlined in CTCAE v5.0 will be used for assessing the severity or intensity of the event. 
The general guidelines for assessing the AE grade appear below. Full guidelines may be obtained at 
http://evs.nci.nih.gov/ftp1/CTCAE. 
 




 
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4. Unlikely related: In general this category can be considered applicable to those AEs which, after 
careful medical consideration at the time they are evaluated, are judged likely to be unrelated to 
the study treatment. An AE may be considered unlikely if or when (must have two): (1) it does 
not follow a reasonable temporal sequence from administration of the study treatment. (2) It 
could not readily have been produced by subject’s clinical state, environmental or toxic factors, 
or other therapies administered to the subject. (3) Disappears or is decreased upon discontinuation 
of the study treatment. (4) It does not follow a known response pattern to treatment with the study 
treatment.  
5. Unrelated: This category applies to those AEs which, after careful consideration at the time they 
are evaluated, are clearly and incontrovertibly due to extraneous causes (disease, environment, 
etc.) and determined with certainty to have no relationship to the study treatment.  
10.1.5 TREATMENT GIVEN AS A RESULT OF THE EVENT 
The event impact in terms of treatment provided will be as either: none, medication administered, non-
medication therapy administered, surgery, or other (with a specification). 
10.1.6 OUTCOME ASSESSMENT 
The outcome of the event will be assessed as either: resolved, resolved with sequelae, ongoing, or death. 
Only one AE per subject is allowed to have an outcome assessment as “death.” If there are multiple 
causes of death for a given subject, only the primary cause of death will have an outcome of death.   
10.1.7 EXPECTED /ANTICIPATED ADVERSE EVENTS 
 
 
 
 
 
 
10.1.8 APPLICATION SITE REACTIONS 
For this population, presence of signs/symptoms similar to application site reactions at the eczema 
lesions at the baseline is expected. Only significant worsening of these signs/symptoms from the baseline 
per the investigator would be considered adverse events.  
 
 
 
 
  




 
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10.4   SAE FOLLOW-UP 
All subjects experiencing an SAE, including the discontinued subjects, must be closely followed until 
sufficient information is obtained to indicate a return to normal status or until the event stabilizes at a 
level acceptable to the investigator (i.e., recovery, return to baseline status, no further improvement 
expected, or death). 
For each SAE indicated as an unresolved event on the initial report, regardless of whether the subject 
completed the study or withdrew, the site should submit a follow-up report with updated information. 
 
 
 


 
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11 DIRECT ACCESS TO SOURCE DATA/DOCUMENTATION 
Subjects will be identified on CRFs by a unique subject identification number and on source documents 
by name and date of birth. No personal identifier will be used in any publication or communication used 
to support this research study. The subject identification number will be used if it becomes necessary to 
identify data specific to a single subject.  
The monitors, auditors, personnel authorized by the Sponsor, the local IRB, and the FDA are eligible to 
review medical and research records related to this study as a part of their responsibility to protect human 
subjects in clinical research and will be given direct access to source data and documentation 
(e.g., medical charts/records, printouts etc.) for source data verification, provided that subject 
confidentiality is maintained in accordance with local requirements. Access to electronic medical records 
may be governed by institution policy and each site will be required to ensure access while remaining 
compliant with institutional requirements. 
 
 
 


 
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12 DATA SAFETY MONITORING COMMITTEE (DSMC) 
In Phase I (Part 1) of the study, the study will be monitored by an independent Data Safety Monitoring 
Committee (DSMC) to ensure patient safety. The CRO is responsible for the overall management of the 
DSMC, including development of its charter and membership selection. The DSMC will be managed in 
conformance with the FDA guidelines for DSMC independence, management, and oversight. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
In Phase II (Part 2) of the study, the DSMC will consider safety data generated during Part 2 of the study 
and to make recommendations about the IA.  
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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13 QUALITY CONTROL AND QUALITY ASSURANCE 
13.1 MONITORING REQUIREMENTS 
In an effort to fulfill the obligations outlined in 21 CFR Part 312 and ICH guidelines which require the 
Sponsor to maintain current personal knowledge of the progress of a study, the Sponsor's designated 
monitor will visit the center(s) during the study as well as maintain frequent telephone and written 
communication. The Investigator will permit the Sponsor to monitor the study as frequently as is deemed 
necessary and provide access to medical records to ensure that data are being recorded adequately, that 
data are verifiable and that protocol adherence is satisfactory.  
The Investigator will permit representatives of the Sponsor and/or designated CRO to inspect all CRFs 
and corresponding study subject original medical records (source documents) at regular intervals 
throughout the study. Subject original medical records and other relevant data must be available to 
support all data recorded in the CRF. In addition to the original medical records, these data may include 
but are not limited to, study, laboratory and diagnostic reports, wound images and tracings, etc.  
Site inspections serve to verify strict adherence to the protocol and the accuracy of the data being entered 
on the CRFs, in accordance with federal regulations. A Monitoring Log will be maintained at each study 
site that the monitor will sign, date, and state the type of visit.  
The Investigator should be aware that the study site and subject records may be inspected by the Sponsor 
and or representatives of the designated CRO, FDA, or other regional regulatory authority. 
The final statistical analysis of data will be performed after all clinical monitoring has been completed, 
all data queries have been resolved, and all data have been verified (Quality Control checked) prior to 
formal database lock. The Sponsor will authorize the final database lock. 
13.2 ACCEPTABILITY OF CASE REPORT FORMS  
All CRFs will be completed as soon as possible after the subject's visit. Corrections to data on the CRFs 
will be made according to standard data correction procedures. The Investigator will review CRFs to 
indicate that, to his/her knowledge, they are complete and accurate. CRFs will be reviewed by the 
Sponsor’s or designated CRO’s monitor, who will make a decision as to their acceptability.   
13.3 MODIFICATION OF PROTOCOL 
The Investigator will not modify or alter this protocol without first obtaining the concurrence of the 
Sponsor. Approval by the Investigator’s IRB must also be obtained prior to implementation of the 
change, with two exceptions: 
 
1. When necessary to eliminate apparent immediate hazard to the subject; or 
2. When the modification does not involve the subject’s participation in the trial. 
 


 
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An amendment may also require modification of the ICF. The Investigator will provide an approval 
letter for the amendment and revised ICF, if applicable, to the Sponsor. An amendment must be in writing 
and it must be dated by both the Sponsor and the Investigator. If necessary, the Sponsor will submit 
protocol amendments to FDA and other appropriate regulatory authorities and notify other Investigators 
using this protocol. 
13.4 REPORTING PROTOCOL DEVIATIONS 
The Investigator is obligated to follow the protocol without departure from the requirements written in 
the protocol. If the Investigator deviates from the protocol requirements, the Sponsor will make the 
determination as to whether the subject will continue in the study. The Sponsor also has the right to 
discontinue the subject for protocol violations. The IRB may also have to be contacted if safety to the 
subject or if the scientific soundness of the study is involved. All protocol deviations must be 
documented in the CRFs. 
 
 
 


 
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14 ETHICS AND REGULATORY REQUIREMENTS 
This study is to be conducted in accordance with the specifications of this protocol and in accordance 
with principles consistent with the Declaration of Helsinki, GCP, 21 CFR 312, ICH E6, HIPAA 
regulations in 45 CFR Part 164, and the Belmont Principles of respect for persons, beneficence, and 
justice. No protocol changes will be implemented without the prior review and approval of the IRB, 
except where it may be necessary to eliminate an immediate hazard to a research subject. In such a case, 
the change will be reported to the IRB as soon as possible, according to IRB regulations. Additionally, 
all study products used in this study are manufactured, handled and stored in accordance with applicable 
Good Manufacturing Practices (GMP) and the products provided for this study will be used only in 
accordance with this protocol. 
14.1 INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE 
The Principal Investigator will provide the Institutional Review Board/Independent Ethics Committee 
(IRB/IEC) with all appropriate materials as required by their IRB/IEC, including but not limited to the 
clinical study protocol, ICFs, and any advertising materials. The study will not be initiated until the 
IRB/IEC provides written approval of the aforementioned documents and until approval documents have 
been obtained by the Principal Investigator and Sponsor or Sponsor designee. The Investigator will not 
participate in the decision. If the Investigator is an IRB or IEC member, documentation must be provided 
indicating recusal from the approval process. Appropriate reports on the progress of this study by the 
Principal Investigator will be made to the IRB/IEC as required by local and applicable government 
regulations and in agreement with policy established by the Sponsor. The Investigator is required to 
maintain an accurate and complete record of all written correspondence to and received from the 
IRB/IEC and must agree to share all such documents and reports with the Sponsor. 
No changes from the final approved protocol will be initiated without the IRB/IEC’s prior written 
approval or favorable opinion of a written amendment, except when necessary to eliminate immediate 
hazards to the subjects or when the change involves only logistics or administration.   
14.2 INVESTIGATOR’S RESPONSIBILITIES 
The Investigators are responsible for performing the study in full accordance with the protocol and the 
current revision of the Declaration of Helsinki, the Good Clinical Practice: Consolidated Guideline, 
approved by the ICH, and any applicable national and local laws and regulations. Information regarding 
any study centers participating in this study that cannot comply with these standards will be documented. 
14.3 SUBJECT INFORMED CONSENT REQUIREMENTS 
Written and oral information about the study in a language understandable by the subject will be given 
to all subjects by the Principal Investigator and/or designee. Written informed consent will be obtained 
from each subject accordingly before any procedures or assessments that would not otherwise be 


 
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required for the care of the subject are done and after the aims, methods, anticipated benefits, potential 
hazards, and insurance arrangements in force are explained and the subject has been given sufficient 
time to ask questions and consider participation in the study. It will also be explained to the subjects that 
they are free to refuse entry into the study and free to withdraw from the study at any time without 
prejudice to future treatment. The written ICF is to be in compliance with CFR 21 Part 50.27, 45 Part 46 
and GCP guidelines. The Sponsor and/or designated CRO will approve the ICF and all amendments to 
the ICF prior to submission to the IRB/IEC. A copy of the ICF to be used will be submitted by the 
Investigator to the IRB/IEC for review and approval prior to the start of the study. Each study site must 
provide the Sponsor with an unsigned copy of IRB/IEC-approved ICF along with applicable 
documentation to support this approval. The original signed ICF is retained in the subject's study records, 
and a copy is provided to the subject. A second copy may be filed in the subject’s medical record, if 
allowed by institutional policy.  
 
 
 


 
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15 DATA HANDLING AND RECORD KEEPING 
15.1 RECORDING AND COLLECTION OF DATA 
The primary source document for this study will be the subject's medical records. If separate research 
records are maintained by the Investigator(s), the medical records and the research records will be 
considered the source documents for the purposes of auditing the study.  
Applicable source data will be manually transcribed to the approved CRFs. The Investigator is ultimately 
responsible for the accuracy of the data transcribed on the forms. All source documents and CRFs will 
be completed as soon as possible after the subject's visit. 
The Investigator will review CRFs to indicate that, to his/her knowledge, they are complete and accurate. 
If further changes are made after this, the Investigator will need to again sign the Investigator signature 
page. Designated source documents will be signed and dated by the appropriate study personnel. The 
Investigator must agree to complete and maintain source documents and CRFs for each subject 
participating in the study. The Investigator will maintain a confidential list of study subjects that will 
include each subject’s study number, name, date of birth and unique hospital identification number if 
applicable. This list will be kept by the Investigator and will not be collected by the Sponsor. A notation 
will be made in the subject’s case history/medical chart that he/she is participating in a clinical study and 
that the subject has provided a signed and dated ICF accordingly as well as the required site HIPAA 
authorization (if separate from the ICF). The Investigator must also maintain a separate screening log of 
all the subjects screened for participation in the study; it should include gender; age; eligibility status; 
reason for ineligibility, if applicable; and study allocated subject number, if applicable.  
15.2 CLINICAL DATA MANAGEMENT 
The Sponsor and/or designated CRO will be responsible for the processing and quality control of the 
data. Data management will be carried out as described in the Sponsor’s or CRO’s standard operating 
procedures (SOPs) for clinical studies. 
The handling of data, including data quality control, will comply with regulatory guidelines (e.g., ICH 
E6 GCP, and local regulations where applicable) and the Sponsor’s or the CRO’s SOPs as well as 
provisions of the study-specific Data Management Plan. All research data will be entered, either 
electronically or manually, into a computerized database, designed in accordance with 21 CFR Part 11 
and based on protocol requirements defined by the Sponsor in association with clinical data manager, 
including double-data entry. The data will be reviewed, manually and/or electronically, and queries will 
be prepared for any data discrepancies. 
15.3 ARCHIVING 
All study documentation at the Investigator site and Sponsor site will be archived in accordance with 
ICH GCP E6 and the Sponsor’s quality standards and SOPs. 


 
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In accordance with CFR 21 Part 312, study records must be retained by the Investigator for at least two 
years (or longer per the state/local regulations) after all investigational use of the product is discontinued 
and the FDA is notified or until two years after the last approval of a marketing application. Study records 
should not be destroyed without prior written agreement between the Sponsor and the study Investigator. 
At the completion of the study, details of the archival process must be provided to the Sponsor. Study 
records are subject to inspection by applicable health and regulatory agencies at any time.   
Records to be retained by the Investigator include, but are not restricted to: 
 Case Report Forms and the source data and the primary records upon which they are based (e.g., 
subject’s progress notes, AE data, test results, and any other diagnostic procedures required to 
evaluate the progress of the study). 
 Signed protocols and protocol amendments 
 Laboratory ranges and certifications  
 Product accountability records 
 Study personnel signature log 
 Monitoring logs 
 Correspondence to and from the Sponsor, designee and IRB 
 Investigator and sub-Investigator CVs 
 Signed informed consent and HIPAA forms 
 Subject screening and randomization log 
 Serious adverse event reports 
 Institutional Review Board approval and re-approval letters 
 Other documents pertaining to the conduct of the study 
These documents must be maintained and kept on file by the Investigator so that the conduct of the study 
can be fully documented and monitored. 
 
 
 


 
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16 PUBLICATION PLAN 
The Investigator will refer to the Investigator agreement and clinical trial agreement for the publication 
and disclosure policy.  
 
 
 


 
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17 REFERENCES 
Alhazmi, Basudan, Moafa et al. Epidemiology of atopic dermatitis among children in Jazan Region, 
Saudi Arabia. Int J of Medical and Health Research. 2017; 3(7):41-45 
 
Badia X, Mascaro JM, et al. Measuring health-related quality of life in patients with mild to moderate 
eczema and psoriasis: clinical validity, reliability and sensitivity to change of the DLQI. Br J 
Dermatol 1999; 141:698-702. 
 
Basra MK, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the Minimal Clinically 
Important Difference and Responsiveness of the Dermatology Life Quality Index (DLQI): Further 
Data. Dermatology. 2015;230(1):27-33. 
 
Eli Lilly and Company. Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-
AD™). International Eczema Council 2017; https://www.eczemacouncil.org/assets/docs/Validated-
Investigator-Global-Assessment-Scale_vIGA-AD_2017.pdf 
 
Ellis CN, Mancini AJ, Paller AS, Simpson EL, Eichenfield LF. Understanding and managing atopic 
dermatitis in adult patients. Semin Cutan Med Surg 2012;31(3 Suppl):S18-22. 
 
Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, et al. Guidelines of 
care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic 
dermatitis. J Am Acad Dermatol. 2014 Feb;70(2):338-51.  
 
Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. Guidelines of 
care for the management of atopic dermatitis: section 2. Management and treatment of atopic 
dermatitis with topical therapies. J Am Acad Dermatol. 2014 Jul;71(1):116-32. 
 
Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity 
index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol. 
2001 Feb;10(1):11-8. 
 
HOME-Harmonising Outcome Measures for Eczema . EASI guidance v3. 2017. Available at 
http://www.homeforeczema.org/documents/easi-user-guide-jan-2017-v3.pdf. Accessed, 2018 
 
Kay J, Gawkrodger DJ, Mortimer MJ, Jaron AG. The prevalence of childhood atopic eczema in a 
general population. J Am Acad Dermatol 1994;30:35-9. 
 
Perkin MR, Strachan DP, Williams HC, Kennedy CT, Golding J, Team AS. Natural history of atopic 
dermatitis and its relationship to serum total immunoglobulin E in a population-based birth cohort 
study. Pediatr Allergy Immunol 2004;15:221-9. 
 
Sidbury R, Davis DM, Cohen DE, Cordoro KM, Berger TG, Bergman JN, et al. Guidelines of care 
for the management of atopic dermatitis: section 3. Management and treatment with phototherapy 
and systemic agents. J Am Acad Dermatol. 2014 Aug;71(2):327-49. 


 
Protocol # AMTX100-AD-01 
Final Version 4.0 
Date: 12-Jul-2023 
 
Confidential 
Page 122 of 124 
18 APPENDICES 
18.1 APPENDIX 1: RELATIVE POTENCIES OF TOPICAL CORTICOSTEROIDS 
Class (TCS) 
Drug 
Dosage form(s) 
Super high 
potency 
Augmented betamethasone dipropionate 0.05% 
Ointment 
 
Clobetasol propionate 0.05% 
Cream, foam, ointment 
 
Diflorasone diacetate 0.05% 
Ointment 
 
Halobetasol propionate 0.05% 
Cream, ointment 
High potency 
Amcinonide 0.1% 
Cream, lotion, 
ointment 
 
Augmented betamethasone dipropionate 0.05% 
Cream 
 
Betamethasone dipropionate 0.05% 
Cream, foam, 
ointment, solution 
 
Desoximetasone 0.25% 
Cream, ointment 
 
Desoximetasone 0.05% 
Gel 
 
Diflorasone diacetate 0.05% 
Cream 
 
Fluocinonide 0.05% 
Cream, gel, ointment, 
solution 
 
Halcinonide 0.1% 
Cream, ointment 
 
Mometasone furoate 0.1% 
Ointment 
 
Triamcinolone acetonide 0.5% 
Cream, ointment 
Medium 
potency 
Betamethasone valerate 0.1% 
Cream, foam, lotion, 
ointment 
 
Clocortolone pivalate 0.1% 
Cream 
 
Desoximetasone 0.05% 
Cream 
 
Fluocinolone acetonide 0.025% 
Cream, ointment 
 
Flurandrenolide 0.05% 
Cream, ointment 
 
Fluticasone propionate 0.05% 
Cream 
 
Fluticasone propionate 0.005% 
Ointment 
 
Mometasone furoate 0.1%  
Cream 
 
Triamcinolone acetonide 0.1% 
Cream, ointment 
Lower-medium 
potency 
Hydrocortisone butyrate 0.1% 
Cream, ointment, 
solution 
 
Hydrocortisone probutate 0.1% 
Cream 
 
Hydrocortisone valerate 0.2% 
Cream, ointment 
 
Prednicarbate 0.1% 
Cream 
Low potency 
Alclometasone dipropionate 0.05% 
Cream, ointment 
 
Desonide 0.05% 
Cream, gel, foam, 
ointment 


 
Protocol # AMTX100-AD-01 
Final Version 4.0 
Date: 12-Jul-2023 
 
Confidential 
Page 123 of 124 
Class (TCS) 
Drug 
Dosage form(s) 
 
Fluocinolone acetonide 0.01% 
Cream, solution 
 
Dexamethasone 0.1% 
Cream 
 
Hydrocortisone 0.25%, 0.5%, 1% 
Cream, lotion, 
ointment, solution 
 
Hydrocortisone acetate 0.5 – 1% 
Cream, ointment 
 
 
 
 
 
 
 
 
 
 



ICF_004.pdf: 
Amytrx Therapeutics, Inc./ Protocol Number AMTX100-AD-01 
Page 1 of 23  
«PiFullName» 
Advarra IRB Approved Version 25/Jul/2023 
Revised «PIApprovalDate» 
INFORMED CONSENT FORM AND AUTHORIZATION TO DISCLOSE HEALTH 
INFORMATION (Part 2) 
Sponsor / Study Title: 
Protocol Number: 
Principal Investigator: 
(Study Doctor) 
Telephone: 
Address: 
Amytrx Therapeutics, Inc./ “A Two-part, Phase I/II, Multi-
center, Double-Blind, Randomized, Vehicle-controlled Study 
of the Safety and Efficacy of topically applied AMTX-100 
CF in adult patients with Mild to Moderate Atopic 
Dermatitis” 
AMTX100-AD-01 (NCT04313400)
«PIFullName» 
«IcfPhoneNumber» 
«PILocations» 
This consent form contains important information to help you decide whether to 
participate in a research study. 
The study staff will explain this study to you. Ask questions about anything that is not clear at 
any time. You may take home an unsigned copy of this consent form to think about and discuss 
with family or friends. 
➢This consent form is for Part 2 (Phase II) of clinical research study, AMTX100-AD-01.
➢Being in this study is voluntary – your choice.
➢If you join this study, you can still stop at any time.
➢No one can promise that a study will help you.
➢Do not join this study unless all of your questions are answered.
After reading and discussing the information in this consent form you should know: 
•
Why this research study is being done;
•
What will happen during the study;
•
Any possible benefits to you;
•
The possible risks to you;
•
Other options you could choose instead of being in this study;
•
How your personal health information will be treated during the study and after the study is
over;
•
Whether being in this study could involve any cost to you; and


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• 
What to do if you have problems or questions about this study. 
 
Please read this consent form carefully. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time.  
(21CFR 50.25(c)). 
 
Introduction 
 
You are being invited to take part in this clinical research study because you have been 
diagnosed with atopic dermatitis (also known as eczema), a skin condition that makes your skin 
red, dry and itchy.  
 
The name of the study drug involved in this study is: 
• AMTX-100 CF3, topical cream, 1.1%  
 
For purposes of this research, you will be referred to as a “participant”.   
 
Amytrx Therapeutics, Inc. (Amytrx), a pharmaceutical company based in U.S., is supporting this 
research study by providing study drug and funding for this research study. 
 
Before you decide to take part in this study, it is important for you to understand why the 
research is being done and what it will involve. This consent form may contain words that you 
do not understand. Please take the time to read the following information carefully and feel free 
to take home an unsigned copy of this consent form to discuss this information with your family, 
friends, relatives and/or your study doctor or other primary care physicians (PCP). Please ask the 
study doctor or one of the study staff to explain any words or information that you do not clearly 
understand. Feel free to request more information about the study.  
 
Once you have this information, understand the study procedures, and have had all your 
questions answered, you will need to decide if you will participate in this study. If you decide to 
participate, you will be asked to sign and date this consent form. Signed and dated copies of the 
consent form will be provided to you. You cannot take part in this research study until you sign 
and date this consent form. 
 
Advarra IRB has approved the information in this consent document and has given approval for 
the study doctor to do the study. An institutional review board (IRB) is an independent 
committee established to help protect the rights of research participants.  This does not mean the 
IRB has approved your participation in the study. You must think about the information in this 
consent document for yourself. You must then decide if you want to be in the study. 
 
What is the purpose of the study? 
 
Your study doctor and his/her colleagues are conducting a research study with Amytrx 
Therapeutics, Inc. (Amytrx) to evaluate whether the study drug (AMTX-100 CF3 in 1.1% w/w 


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concentration) topical cream is safe and efficacious when used to treat Atopic Dermatitis 
(eczema). Atopic dermatitis (eczema) is a condition that makes your skin red, dry and itchy. This 
study drug is investigational because it has not been approved by the U.S. Food and Drug 
Administration (FDA). The results of these studies will be used to design future studies to 
improve treatment of atopic dermatitis. 
 
Previous animal and pre-clinical studies have suggested that the study drug is both effective in 
treating eczema-like lesions on animals, and safe at the doses proposed for human use. As for 
previous human clinical trials, Part 1 (Phase I) of this study has been completed already, in 
which 26 participants with atopic dermatitis were enrolled and applied the study drug twice daily 
for 1 week. The study results showed the study drug was both safe and efficacious in treating 
atopic dermatitis lesions.  
 
Part 2 (Phase II) of the study (current study you are considering) will further explore the safety 
and efficacy of the investigational drug (AMTX-100 CF3 topical cream, which includes 1.1% of 
the active ingredient AMTX-100), in improving symptoms of atopic dermatitis compared to 
placebo (topical cream with 0% of the active ingredient AMTX-100).  
 
How does AMTX-100 CF3 work? 
 
Atopic dermatitis (AD) is a common, chronic, non-infectious skin condition. The main symptom 
of this inflammatory disease is a very itchy rash. The itch leads to scratching, and more redness, 
swelling, cracking, leaking clear fluid, crusting, and scaling. 
 
In many cases AD gets better as the years go by, and it may go away for a while or disappear 
altogether. AD flare-ups (getting worse at times) however can really affect quality of life. People 
with AD tend to have an over-reactive immune system that when triggered by a substance 
outside or inside the body, responds by producing inflammation. It is this inflammation that 
causes the red, itchy and painful skin symptoms.  
 
AMTX-100 CF3 study drug product is a white cream with AMTX-100, a new class of medicines 
which target body’s inflammatory responses. AMTX-100, the active ingredient, is a peptide (a 
type of protein), which reduces the inflammatory responses within your skin cells, thus reducing 
eczema symptoms. In this study, AMTX-100 CF3 topical cream or placebo with 0% of active 
ingredient will be applied to the eczema affected areas of your skin twice daily for twenty-eight 
(28) consecutive days.  
 
This document uses words such as study treatment, study drug, medication, and participant. Please 
remember this is a research study and the use of these terms does not mean the use of AMTX-100 
CF3 has been found to be safe or effective for your condition. 
 
Why have I been chosen? 
 
You have been chosen for consideration for this study because you are diagnosed with atopic 
dermatitis (AD), also known as eczema, and your study doctor thinks that you might be a good 
candidate for this study, based on how severe and how large your skin areas are affected by AD. 


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In this study, about 60 participants with atopic dermatitis will enroll at about 20 sites within the 
United States. 
 
Do I have to take part? 
 
You do not have to take part in this study; it is completely voluntary. You will always be free to 
withdraw from the study at any time. If you withdraw during the study, you will be asked to 
come in for a final visit for study evaluations. You do not have to give a reason for your 
withdrawal from the study. This will not affect the standard of care that you will receive, and it 
will not result in any penalty or loss of benefits to which you are entitled. The data collected up 
to that point will be kept with your medical records and will be kept confidential. Your identity 
will not be disclosed. 
 
General Study Design and Duration of Study Involvement 
 
The duration of your participation in this study will be approximately up to ten (10) weeks and 
includes seven (7) in-clinic study visits to the study center. The study will be conducted in 3 
Parts. After the initial screening period (up to 4 weeks), you will enter study treatment period (28 
days), followed by the follow-up period (around 2 weeks).  
 
Screening Period: 
During this part of the study, you will be evaluated to determine if you would be eligible to enter 
the study. The Screening phase will take up to 4 weeks.  
 
Study Treatment Period: 
Participants who are determined to be eligible will enter the study treatment period of the study. 
During this part of the study, fifty-six (56) total doses of the study treatment (either AMTX-100 
CF3 topical cream, 1.1%,  or placebo) will be applied to all the AD-affected areas (except the 
scalp, face, eyes, eyelids, hands, palms, feet, groin, genitals or in the axillae) as instructed by the 
study doctor, in 1 dose applied twice daily for 28 consecutive days, regardless of whether your 
AD affected skin areas become better or clear. Study treatment period will be “Double-Blinded”, 
meaning that neither you nor the study doctor will know which study treatment group you have 
been randomly assigned to. 
 
At the first study visit of the study treatment period, you will be randomly assigned (by chance) 
to one of two (2) different groups to receive AMTX-100 CF3 topical cream (with 1.1% active 
ingredient of AMTX-100), or placebo (with no active ingredient) twice daily for 28 days. After 
the first visit of the study treatment period, you will be required to come to the study site for 
study visits once every week at weeks 1, 2, 3, and 4. 
 
At the week 4 Visit, all participants who have successfully completed study treatment period of 
the study will continue to the follow-up period of the study. 
 
Follow-up Period: 
After successful completion of the previous parts of the study, you will enter the follow-up period 
of the study to further assess how safe and whether the investigational drug AMTX-100 CF3 works 




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• While you apply study drug, 
o Avoid removing or occluding the study treatment by wearing loose-fitting 
clothing  
o Avoid wiping your skin 
o Avoid swimming after application 
o Bathing the treated areas will be allowed once daily and should be done at least 
every 3 days 
o Bathing/washing the treated areas in between morning and evening dose should 
be avoided within 8 hours after application 
• 
You may have some help from others when you apply the study topical cream for skin 
areas which are hard to reach. 
• 
Record study treatment and moisturizer administration information in your patient diary, 
as instructed by the study staff, and return your patient diary and used study drug tubes to 
the study site.  
• 
Report any changes in your health or medications to the study doctor. You should not 
make any changes in your medications for atopic dermatitis unless instructed by the study 
doctor. In case your study doctor initiates any treatment for worsening symptoms of 
atopic dermatitis, ensure that you follow the treatment, instructed by the study doctor;  
• 
There will be no restriction of what you can eat during the study, unless food items are 
known to yourself or study doctor to trigger AD symptoms. 
• 
If you are a woman of childbearing potential, you must use an acceptable method of birth 
control (for example, diaphragm, intrauterine device (IUD), condom, hormonal 
contraceptives, or abstinence) during your participation in the study or be surgically 
sterile (for example, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), so 
that you do not become pregnant. If you are found to be pregnant after you receive first 
dose of study drug, your participation in the study will be terminated, but your pregnancy 
will be followed up to term to evaluate if there are any safety concerns with you or your 
child. 
• 
If for any reasons you are withdrawn from the study, withdrawal visit and follow up visit 
assessments will be performed. 
 
Research Study Visits, Procedures and Assessments 
 
Screening Part: 
 
Screening Visit (Visit 1) 
At the Screening Visit, the study doctor will check to see if you are eligible to participate in this 
study. After you sign and date this informed consent form and receive a copy, the following 
procedures will be done at the screening visit. If you are not eligible for the study, the study 
doctor will explain the reasons and arrange for the prescribed standard conventional therapy to 
continue. 
 
The following procedures will be performed during the “Screening Visit (Visit 1)”: 


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This visit will take about 2-3 hours of your time. 
 
If the results from the “Screening Visit” procedures are acceptable to the study doctor, you 
will be scheduled for study treatment part. 
 
Study Treatment Part: 
 
Visit 2 (Baseline): Day 0 
 
Visit 2 will occur within 28 days after the Screening Visit. At Visit 2, the study doctor will check 
to see if you continue to be eligible to participate in this study. If you are not eligible for the study, 
the study doctor will explain the reasons and arrange for the prescribed standard conventional 
therapy to continue. If you continue to be eligible for the study, you will continue the study and 
procedures will be conducted as outlined below: 
 
Below procedures will be performed at Visit 2 (Baseline), before you receive any study 
drug: 
 
 
 
 
 
  


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The Study Treatment Groups are:  
 
• Group A (AMTX-100 CF3): One group will receive AMTX-100 CF3 (including 
the active ingredient AMTX-100 1.1%), to be topically applied twice a day for 28 
consecutive days  
• Group B (Placebo (Vehicle)): The other group will receive placebo (with no active 
ingredient), topically applied twice a day for 28 consecutive days  
 


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Neither you nor your study doctor will know which group you have been assigned to. 
Both the active study drug and placebo will look the same.  
 
 
 
 
 
 
 
 
 
 
 
 
After First Study Drug Application 
Your study doctor will monitor your condition, any possible side effects and the study treatment 
regimen as described below: 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
This visit will take about 2-3 hours of your time. 
 


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Treatment Visit 3, 4, 5, and 6 (Day 7, Day 14, Day 21, and Day 28±1 days) 
At visits 3, 4, 5 and 6 the study evaluations will continue, and your study doctor will monitor 
your condition, any possible side effects and the study treatment schedule as described below: 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  


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 This visit will take about 2-3 hours of your time. 
 
Follow-Up Part: 
After completion of Visit 6 or early termination procedures (if you withdrew early from the 
study), all participants will be followed up for 2 weeks to further assess safety and efficacy of 
study treatment. 
 
Follow-Up Visit (Visit 7: Day 2±3) 
During the follow-up visit, the following assessments will be performed: 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  


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This visit will take about 1-2 hours of your time. 
 
Withdrawal Visit: 
For participants who withdraw/are discontinued prematurely during study treatment period, 
“Withdrawal visit” assessments will be performed. Visit 6 assessments will be performed as the 
withdrawal visit evaluations. For all withdrawn/discontinued participants during study treatment 
period, the Follow-up visit (Visit 7) will happen 2 weeks after the withdrawal visit evaluations.  
 
What are the risks of taking part? 
 
AMTX-100 CF3 topical cream is still undergoing testing and there may be side effects that are 
unknown at this time.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Animal and clinical studies have not indicated that AMTX-100 or AMTX-100 CF3 topical 
administration might be associated with allergic reactions. To reduce the risk of skin irritation, 
bathing the treated areas will be allowed once daily. Bathing/washing the treated areas in 
between morning and evening dose should be avoided within 8 hours after application and 
should be done at least every 3 days keeping normal daily hygiene. 
 
You will be monitored carefully during the administration of study drugs and will be watched 
carefully for side effects or any allergic reactions. As with any study drug, there is a risk of 


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allergic reaction. If you have a very serious allergic reaction, you may be at risk of death. Some 
symptoms of allergic reactions are: 
• 
Rash 
• 
Wheezing and difficulty breathing 
• 
Dizziness and fainting 
• 
Swelling around the mouth, throat or eyes 
• 
A fast pulse 
• 
Sweating 
You need to tell your study doctor or study staffs immediately if you experience any side 
effects, any unfavorable signs or symptoms. If any safety concerns arise, the study treatment 
may be stopped.  
 
Some redness, faintness, pain and swelling may happen due to the blood draws. You may 
experience bruising or bleeding at the site where the needle was placed. There is also a slight 
possibility of infection. 
 
If you do not understand what any of these side effects mean, please ask the study doctor or the 
study staff to explain them to you. 
 
It is unknown whether or not AMTX-100 CF3 topical cream will have any effect on unborn 
children or babies. It is unknown if AMTX-100 can pass through breast milk and it is unknown if 
this can cause harm to your child. This has not yet been investigated. Therefore, females who are 
pregnant or planning on becoming pregnant or who are breastfeeding will not be included in the 
study. If you are a woman of childbearing potential, you must use an acceptable method of birth 
control (for example, diaphragm, intrauterine device, condom, hormonal contraceptives, or 
abstinence) during your participation in the study or be surgically sterile (for example, 
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), so that you do not become 
pregnant. If you become pregnant during the study, please inform one of the study staff as soon 
as possible. Your pregnancy will be followed up to term. 
 
Your symptoms associated with atopic dermatitis may not get better or may become worse 
during this study. 
 
What are the possible benefits of taking part? 
 
You may or may not directly benefit from taking part in this study. The study treatment you 
receive may help to improve your atopic dermatitis symptoms. However, this cannot be 
guaranteed. The information that we get from this study may help us, and your study doctor, to 
treat future patients with this disease in a better way. 
 
Are there costs for participating?  
 
All study procedures will be provided at no charge to you. 
 
Reimbursement for study participation: 
«Compensation» 




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concerns. The name and phone number of your study doctor is printed on the first page of this 
consent form. 
 
If you experience a side effect or injury that may be related to this study or if you have an 
unscheduled visit for medical care for any reason, please contact the study doctor listed on page 
one of this informed consent. 
 
If you claim to have become sick or injured from participating in this study, Amytrx 
Therapeutics, Inc. may give information that identifies you to its insurance carrier.  This 
information will be used by the insurance carrier solely for the purpose of resolving your claim. 
To pay medical expenses, the sponsor will need to know some information about you like your 
name, date of birth, and Medicare Beneficiary Identifier (MBI). This is because the sponsor has 
to check to see if you receive Medicare and if you do, report the payment it makes to Medicare. 
 
Will my taking part in this study be kept confidential? 
 
If you agree to take part in this study, your identity and medical records will be kept confidential 
and will not be disclosed outside of the hospital/study site/family physician’s office unless 
required by law. Your medical records may be inspected by Amytrx Therapeutics, Inc (the 
company sponsoring the study). Your records may also be inspected by a company Amytrx 
Therapeutics, Inc has delegated some study management to, Amarex Clinical Research, LLC. 
(Amarex), for purposes of analyzing the study results and monitoring the study. Regulatory 
authorities such as the U.S. Food and Drug Administration (FDA) and Institutional Review 
Boards (IRB) may review study results and participants records to check that the study is being 
conducted correctly. This means that absolute confidentiality cannot be guaranteed. If the results 
of this study are published or presented at meetings, you will not be identified. 
 
What if new information becomes available? 
 
During the course of a research study, new information may become available about your disease 
or the study treatment that is being studied that might change your decision to be in this study. If 
this happens, your study doctor will discuss this with you and whether you want to continue in 
the study. If you decide to withdraw, your study doctor will make arrangements for your 
prescribed standard conventional therapy to continue. If you decide to continue in the study you 
will be asked to sign and date an updated consent form. 
 
Also, on receiving new information your study doctor might consider it to be in your best interest 
to withdraw from the study. The study doctor will explain the reasons and arrange for your 
prescribed standard care to continue. 
 
What will happen to the results of the research study? 
 
Once the study has finished, the information will be analyzed, and a clinical study report will be 
written to record the results. This process can take about 6 months. Your study doctor will be 
kept informed of the results from the study, and a paper detailing these results will probably be 


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published in an appropriate medical journal. You can also ask the study doctor for the results of 
the study. 
 
Who is organizing and funding the research? 
 
The company sponsoring and funding this research study is Amytrx Therapeutics, Inc. The study 
site and/or your study doctor is receiving financial support from the sponsor for undertaking this 
study. 
Voluntary participation / Withdrawal 
 
Your participation in this study is voluntary. You may decide not to participate or may leave the 
study at any time. Your decision will not result in any penalty or loss of benefits to which you 
are entitled. Tell the study doctor if you are thinking about stopping or have decided to stop. The 
study doctor will tell you how to stop your participation safely.  
 
It is important to tell the study doctor if you are thinking about stopping your participation so 
that your study doctor can evaluate any risks from the study drug and discuss what alternative 
follow-up care and testing could be most helpful for you. If you withdraw during the study, you 
will be asked to come in for withdrawal visit, followed by safety follow up visit for safety 
reasons. Even if you don’t want to return for follow-up visits and blood tests, we would still like 
to collect information by phone or available medical records about your disease status. 
 
Early Termination: 
Your participation in this study may be stopped at any time by the study doctor, the sponsor 
(Amytrx Therapeutics, Inc.), the FDA, and/or the IRB without your consent for any of the 
following reasons: 
• 
If it is in your best interest 
• 
If you do not consent to continue in the study after being told of changes in the research 
that may affect you 
• 
If you do not follow research directions 
• 
If you experience any serious side effects to the study drug 
• 
If lost to follow-up 
• 
If you are found to be pregnant 
• 
If the study is stopped early by the Sponsor (Amytrx), the IRB, the independent Data 
Safety Monitoring Committee (DSMC) or any regulatory agencies such as the U.S. Food 
and Drug Administration (FDA) 
• 
Administrative reasons 
• 
Or any other reason as determined by the study doctor or the study sponsor. 
 
WHOM TO CONTACT ABOUT THIS STUDY 
During the study, if you experience any medical problems, suffer a research-related injury, or 
have questions, concerns or complaints about the study, please contact the Investigator at the 
telephone number listed on the first page of this consent document. If you seek emergency care, 


Amytrx Therapeutics, Inc./ Protocol Number AMTX100-AD-01  
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«PiFullName» 
Advarra IRB Approved Version 25/Jul/2023 
Revised «PIApprovalDate» 
 
or hospitalization is required, alert the treating physician that you are participating in this 
research study.  
 
An institutional review board (IRB) is an independent committee established to help protect the 
rights of research participant. If you have any questions about your rights as a research 
participant, and/or concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Subject Adviser 
Advarra IRB 
 6100 Merriweather Dr., Suite 600 
 Columbia, MD 21044 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Subject Adviser: 
Pro00042081. 
 
 
 


Amytrx Therapeutics, Inc./ Protocol Number AMTX100-AD-01  
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«PiFullName» 
Advarra IRB Approved Version 25/Jul/2023 
Revised «PIApprovalDate» 
 
PRIMARY HEALTH CARE PROVIDER NOTIFICATION OPTION 
 
I consent to having my family doctor or primary health care provider notified by the study site of 
my participation in this study and/or any significant findings related to my health (please check 
yes or no). 
 
 Yes (If yes, please complete the information below) 
 No   
 I do not have a primary care physician/specialist. 
 The study doctor is my primary care physician/specialist. 
 
Name and address of family 
doctor or primary health care 
provider: 
Name: 
Address: 
 
Telephone  
Tel: 
 
 
 
 
 
Do not sign and date this consent form unless you have had a chance to ask questions and have 
received satisfactory answers to all of your questions. 
 
If you agree to be in this study, you will receive a signed and dated copy of this consent form for 
your records. 
 
If you choose to participate in this study, please read the following and sign and date where 
indicated. 
 
 
 
 
 
 
 
 
 
 
 
 


Amytrx Therapeutics, Inc./ Protocol Number AMTX100-AD-01  
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«PiFullName» 
Advarra IRB Approved Version 25/Jul/2023 
Revised «PIApprovalDate» 
 
PARTICIPANT STATEMENT OF CONSENT 
 
I confirm that I have read this consent form (or it has been read to me) and the content of this 
form has been explained to me. I confirm that I have had the opportunity to ask questions and all 
of my questions were answered to my satisfaction. I agree to participate in this study and comply 
with the requirements to the best of my ability. 
 
My participation in this study is voluntary and I AM free to withdraw at any time, without giving 
any reason, without my medical care or legal rights being affected. 
 
I agree to take part in the above study. 
 
I consent to the use of all anonymized data that is collected from me during this study being 
used, either individually or pooled with other participants, in the analysis of this study, in printed 
publications, or for other purposes as determined by the sponsor, Amytrx Therapeutics, Inc. (The 
word Anonymized means that it will not be possible for you to be identified from the data that is 
collected). 
 
By signing and dating this consent form, I have not given up any of my legal rights. 
 
 
 
 
Printed Name of Participant 
 
 
________________________ 
____________ 
__________ 
Participant’s Signature 
Date 
Time 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Amytrx Therapeutics, Inc./ Protocol Number AMTX100-AD-01  
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«PiFullName» 
Advarra IRB Approved Version 25/Jul/2023 
Revised «PIApprovalDate» 
 
STATEMENT OF PERSON CONDUCTING INFORMED CONSENT DISCUSSION 
AND THE INVESTIGATOR 
 
I, the undersigned, certify that to the best of my knowledge that participant named above had the 
study fully and carefully explained, including the nature, risks, and benefits of his/her 
participation in the research study; and all questions were answered to the study participant’s 
satisfaction. I confirm that the study participant freely and voluntarily gave consent to participate 
in this research study before any study-related procedures were performed. A medical problem or 
language or educational barrier has not precluded this understanding. 
 
I reviewed the consent form with the participant and answered the participant’s questions. The 
participant appeared to have understood the information and was able to answer the following 
questions correctly: 
 
1. What is the purpose of this study? 
2. If you decide to be in the study, what will you be asked to do? 
3. What is the possible benefit of participating in this study? 
4. What are the possible risks of participating in this study? 
5. If you decide not to participate in this study, what options do you have? 
6. Will participating in this study cost you anything? If so, what will you have to pay for? 
7. Do you have to be in this study? 
8. If you decide to be in the study, can you leave the study when you want to? 
 
 
 
 
 
____________ 
__________ 
Signature of Person Conducting 
          Date                      Time 
Informed Consent Discussion 
 
 
 
 
Name of Person Conducting Informed Consent 
Discussion (if different from Study Doctor) 
 
 
I, the undersigned, certify that to the best of my knowledge the study participant named above 
had the study fully and carefully explained, including the nature, risks, and benefits of the 
participant’s participation in the research study. 
 
 
______________________ 
__________ 
__________ 
Signature of Study Doctor 
Date 
Time 
(If different from above) 
 
Original copy to be kept with the study doctor; one copy to be given to the participant; one 
copy to be kept with the participant’s medical records. 
 


Amytrx Therapeutics, Inc./ Protocol Number AMTX100-AD-01  
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«PiFullName» 
Advarra IRB Approved Version 25/Jul/2023 
Revised «PIApprovalDate» 
 
Authorization to Use and Disclose Protected Health Information (HIPAA 
Authorization) 
 
While you are participating in this research study, the study doctor and his/her 
study staff will collect and create personal health information about you and record 
it on study forms. This information may include health histories, examinations, and 
results of tests. The study doctor will keep this information in study records. 
He/she may also gather information regarding your past, present, and/or future 
medical conditions from your primary medical doctor. These records may also 
include personal information such as your birth date, social security number, or 
medical record numbers which could be used to identify you. This type of 
information is called “Protected Health Information” (PHI). 
 
Under a United States federal law called the “Privacy Rule” or Health Insurance 
Portability and Accountability Act of 1996 (HIPAA), no one’s PHI that is gathered 
and obtained during research can be used to conduct the research or be given to 
anyone for research purposes without one’s permission. Because of this rule, you 
may not participate in this study unless you give your permission to use and 
disclose your PHI. 
 
By signing and dating this authorization, you are giving permission for the study 
doctor and his/her study staff, along with the Sponsor (Amytrx Therapeutics), 
Amarex Clinical Research (the Contract Research Organization) and the 
Regulatory authorities such as the U.S. Food and Drug Administration (FDA) and 
Institutional Review Boards (IRB) to use your PHI to conduct this study, to 
monitor your health status, and possibly to develop new tests, procedures, and 
commercial products.  
 
You are also agreeing to allow your PHI to be disclosed to the study sponsor and 
any representatives working with them. The sponsor may also give your PHI to the 
FDA or other regulatory agencies. Study staff will assign a code number to you for 
this study. This will help to protect your identity; however, the sponsor may look at 
your complete study records which will identify you. The sponsor will also send 
representatives to your study doctor’s office to oversee how the study is being 
conducted. These representatives will review your PHI to make sure the 
information is correct. The IRB may also have access to your PHI to meet its 
oversight responsibilities. These disclosures help to make sure that all information 
related to the research is available to those who need it. 
 


Amytrx Therapeutics, Inc./ Protocol Number AMTX100-AD-01  
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«PiFullName» 
Advarra IRB Approved Version 25/Jul/2023 
Revised «PIApprovalDate» 
 
Your identity will remain confidential, except for the disclosures described above 
and detailed specifically in the consent page, and will not be shared with others, 
unless it is required by law. If your PHI is given to the parties listed above or to 
anyone who is not required to follow federal law, your PHI will no longer be 
protected by the “Privacy Rule” and could possibly be used or disclosed in ways 
other than those listed here. 
 
You have the right to see and make copies of your PHI. You are agreeing, 
however, not to see or make copies of your PHI until all of the sponsor work has 
been completed. At that time, you may ask to see your records. 
 
Your HIPAA Authorization will expire 50 years from the date you sign it unless 
you revoke (cancel or withdraw) it sooner. You have the right to cancel or 
withdraw this authorization at any time. If you cancel this authorization, your PHI 
will no longer be used for this study, unless it is necessary (based on your earlier 
authorization) to complete analysis (tests) and reports for this research. 
 
To cancel your permission to use PHI, you must send a written notice to your study 
doctor’s office at the address listed on page one stating that you are canceling your 
authorization for them to use or disclose your protected health information. If you 
cancel this authorization, you will not be allowed to continue in this study. 
 
Participants will receive a signed and date copy of this document. 
 
 
 


Amytrx Therapeutics, Inc./ Protocol Number AMTX100-AD-01  
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«PiFullName» 
Advarra IRB Approved Version 25/Jul/2023 
Revised «PIApprovalDate» 
 
AUTHORIZATION 
 
I authorize the use and disclosure of my health information to the parties listed in 
the HIPAA authorization for the purposes described above. 
 
 
___________________________________ 
Printed Name of Participant (Study Participant) 
 
 
________________________ 
____________ __________ 
Participant’s Signature 
Date 
Time 
 
 
____________________________________ 
Printed Name of the Person Obtaining the  
Authorization 
 
 
____________________________________ 
 
__________ 
Signature of the Person Obtaining the  
 
 
Date 
 
Original copy to be kept with the researcher; one copy to be given to the participant; one 
copy to be kept with the participant’s medical records. 
 

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN  
FOR PROTOCOL AMTX100-AD-01 
Sponsor: 
Protocol Number: 
Protocol Title: 
Amytrx Therapeutics, Inc. 
AMTX100-AD-01 (NCT04313400)
A Two part, Phase I/II, Multi-center, Double-Blind, 
Randomized, Vehicle-controlled Study of the Safety and 
Efficacy of Topically Applied AMTX-100 CF in Adult 
Patients with Mild to Moderate Atopic Dermatitis  
Protocol Version / Date: 
Final Version 4.0/ 12 Jul 2023 
SAP Author: 
Amarex Clinical Research, 
LLC 
20201 Century Boulevard 
Germantown, MD   20874 
USA 
Telephone:   1-866-AMAREX-1 
1-301-528-7000
Facsimile: 
1-301-528-2300 
Study Part 
Part 2 
Plan Version: 
Final Version 1.0 
Plan Date: 
29 Aug 2023 
--- confidential--- 


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Protocol Number:  
AMTX100-AD-01 
Protocol Version / Date: 
Final Version 4.0/ 12 Jul 2023 
Protocol Name: 
A Two part, Phase I/II, Multi-center, Double-Blind, 
Randomized, Vehicle-controlled Study of the Safety and 
Efficacy of Topically Applied AMTX-100 CF in Adult 
Patients with Mild to Moderate Atopic Dermatitis 
 
Sponsor: 
Amytrx Therapeutics, Inc.  
Prepared by: 
Amarex Clinical Research 
20201 Century Boulevard 
Germantown, Maryland  20874 
Study Part: 
Part 2  
SAP Version: 
Final Version 1.0 
SAP Date: 
29 Aug 2023 
 
 
I have read and approve the Statistical Analysis Plan specified above and agree on its 
content: 
 
 
 
 
Statistician, Amarex Clinical Research 
 
Date 
 
 
 
Amytrx Therapeutics, Inc. Representative 
 
Date 


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TABLE OF CONTENTS 
 
Section   
Page 
ABBREVIATIONS, ACRONYMS, AND DEFINITIONS ................................................................. 5 
1. 
INTRODUCTION ............................................................................................................... 6 
2. 
PROTOCOL DESIGN ......................................................................................................... 6 
2.1 
Design Overview ...................................................................................................... 6 
2.2 
Treatment Groups ................................................................................................... 10 
2.3 
Randomization and Stratification ............................................................................. 10 
2.4 
Blinding ................................................................................................................. 10 
2.5 
Time to Unblinding................................................................................................. 10 
2.5.1 
Interim Analysis/ DSMC ............................................................................ 10 
2.5.2 
Emergency Un-Blinding ............................................................................. 11 
2.5.3 
Final Analysis ........................................................................................... 11 
2.6 
Protocol Objective(s) .............................................................................................. 11 
2.7 
Efficacy Assessments/ Outcome Measures ................................................................ 11 
2.7.1 
Primary Efficacy Outcome Measure ............................................................ 11 
2.7.2 
Secondary Efficacy Outcome Measures ....................................................... 11 
2.7.3 
Exploratory Outcome Measures .................................................................. 12 
2.7.4 
Safety Assessments .................................................................................... 13 
3. 
SAMPLE SIZE DETERMINATION, STATISTICAL POWER, AND SIGNIFICANCE 
LEVEL .............................................................................................................................. 13 
4. 
INTERIM ANALYSIS ....................................................................................................... 13 
4.1 
Goals ..................................................................................................................... 13 
4.2 
Analysis Population ................................................................................................ 13 
4.3 
Procedures for Data Preparation  .............................................................................. 13 
4.4 
Rules and processes for IA Decisions, Stopping Rule ................................................ 14 
4.5 
Data Provided to DSMC .......................................................................................... 14 
4.6 
Information Provided to Sponsor by DSMC .............................................................. 14 
5. 
PRIMARY HYPOTHESIS TO BE TESTED ..................................................................... 14 
6. 
ANALYSIS POPULATIONS ............................................................................................. 14 
6.1 
Efficacy Evaluable Population ................................................................................. 14 
6.2 
Intent-to-Treat (ITT) population ............................................................................... 14 
6.3 
Safety Population ................................................................................................... 15 
7. 
DATA CONVENTION AND RELATED DEFINITIONS .................................................. 15 
7.1 
Baseline Definition ................................................................................................. 15 
7.2 
Duplicate Data ....................................................................................................... 15 
7.3 
Handling of Missing Data ........................................................................................ 15 
7.3.1 
Handling of Missing Data for Efficacy Evaluations ...................................... 15 
7.3.2 
Use of Rescue Treatment(s) ........................................................................ 15 
7.3.3 
Handling of Missing Data for Safety Evaluations ......................................... 15 
7.4 
Multicenter Clinical Trials ....................................................................................... 16 
7.5 
Multiple Comparisons and Multiplicity .................................................................... 16 
7.6 
Covariates and Prognostic Factors ............................................................................ 16 
7.7 
Subgroups .............................................................................................................. 16 




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ABBREVIATIONS, ACRONYMS, AND DEFINITIONS 
Abbreviation/Acronym 
Definition 
ADSL 
Subject-Level Analysis Dataset 
ALP 
Alkaline Phosphatase  
ALT 
Alanine Aminotransferase 
Amarex 
Amarex Clinical Research, LLC. 
ASA 
The American Statistical Association 
AST 
Aspartate Aminotransferase 
BID 
Twice a Day 
BMI 
Body Mass Index 
BSA 
Body Surface Area 
BUN 
Blood Urea Nitrogen 
CRO 
Contract Research Organization 
CTCAE 
Common Terminology criteria for Adverse events 
CSR 
Clinical Study Report 
DLQI 
Dermatology Life Quality Index 
DSMC 
Data Safety and Monitoring Committee 
EASI 
Eczema Area Severity Index 
ECG 
EDC 
Electrocardiogram 
Electronic Data Capture 
IA 
Interim Analysis 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonization 
MCH 
Mean Corpuscular Hemoglobin 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MTD 
Maximum Tolerable Dose 
Pruritus NRS 
Pruritus Numeric Rating Scale 
RBC 
RNA 
Red Blood Cells 
Ribonucleic Acid 
SAP 
Statistical Analysis Plan 
SAS® 
Statistical Analysis System 
SOC 
System Organ Class 
SOP 
Standard Operating Procedures 
TCS 
TSLP 
Topical Corticosteroids 
Thymic Stromal Lymphopoietin 
TEAE 
TARC 
Treatment Emergent Adverse Event 
Thymus and Activation-Regulated Chemokine 
USA 
United States of America 
vIGA-AD™ 
Validated Investigator Global Assessment scale for Atopic Dermatitis 
WBC 
White Blood Cells 
WHO 
World Health Organization 
 


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1. 
INTRODUCTION 
This Statistical Analysis Plan describes the planned analyses and reporting for part 2 of  the 
clinical trial protocol AMTX100-AD-01, conducted by Amytrx Therapeutics, Inc.. The 
reader of this Statistical Analysis Plan (SAP) is encouraged to review the complete protocol 
and amendments as this plan contains only a limited overview of protocol information.  
The main objectives of this plan are to provide details pertaining to statistical methodology, 
data conventions, and processes used for the analysis of data from this trial.  
The format and content of this SAP are structured to provide sufficient detail to meet the 
requirements specified by the International Council on Harmonization (ICH) E9: Guidance 
on Statistical Principles in Clinical Trials.  All work planned and presented in this Statistical 
Analysis Plan will follow the ethical guidelines published by the American Statistical 
Association (ASA). 
The following documents were reviewed in preparation of this Statistical Analysis Plan: 
• Final protocol Version 4.0/ 12 Jul 2023 
• ASA Ethical Guidelines for Statistical Practice (2016) 
• The Royal Statistical Society: Code of Conduct (2014) 
• ICH Guidance on the Structure and Content of Clinical Study Reports (ICH E3, 1996) 
• ICH Guidance on the Structure and Content of Clinical Study Reports (ICH E3(R1), 
2013) 
• ICH Guidance on the Statistical Principles for Clinical Trials (ICH E9, 1998) 
• ICH Guidance on the Statistical Principles for Clinical Trials (ICH E9(R1), 2017) 
2. 
PROTOCOL DESIGN 
2.1 
Design Overview 
This is an adaptive, Phase I/II study in 2 parts: Part 1 (Maximum Tolerable Dose (MTD) 
Finding by maximum percentage of BSA treated) and Part 2 (evaluating efficacy of 
AMTX-100 CF3 1.1% w/w versus placebo (vehicle)). The Part 1 of the study has been 
completed.  
Phase II (Part 2) Study Design 
Phase II (Part 2) of this study is a multi-center, double-blind, randomized, vehicle-
controlled study of the safety and efficacy of topically applied AMTX-100 CF3 in adult 
patients with Mild to Moderate AD. Sixty (60) subjects will be enrolled in two groups of 
AMTX-100 CF3 1.1% w/w and placebo (vehicle). The subjects will be randomized in a 
1:1 ratio, thus thirty (30) subjects will be randomized to Group A (AMTX-100 CF3 1.1% 
w/w) and thirty (30) subjects will be randomized to Group B (placebo (vehicle 0% w/w)). 
Each enrolled subject, after screening and randomization, will receive AMTX-100 CF3 
1.1% w/w or placebo (vehicle) to be applied twice daily to all treatable AD lesions 
regardless of whether the AD lesions become clinically clear or not (excluding the scalp, 
face, eyes, eyelids, hands, palms, feet, groin, genitals or in the axillae) for 28 consecutive 




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2.7.4 Safety Assessments 
• Incidence of Treatment-Emergent Adverse Events (TEAE) 
• Incidence of withdrawals from the study due to TEAEs 
• Changes from baseline in study treatment application site reaction assessment 
• Changes and shifts in laboratory measurements over time 
• Changes in vital signs over time 
3. 
SAMPLE SIZE DETERMINATION, STATISTICAL POWER, AND 
SIGNIFICANCE LEVEL 
The sample size of 60 subjects for Phase II of this study is selected on the basis of clinical 
judgment and not based on statistical power calculation. The number of subjects is deemed 
adequate to provide clinically meaningful results consistent with study objectives. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
   
 
  
 
 
  


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5. 
PRIMARY HYPOTHESIS TO BE TESTED 
There is no formal hypothesis testing for this study as the study is a Phase II evaluation and 
is not intended to be hypothesis generating. The study is not powered to reliably yield 
statistically significant conclusions. 
6. 
ANALYSIS POPULATIONS  
 
   
 
 
 
 
 
 




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7.4 
Multicenter Clinical Trials  
This is a multi-center clinical trial.  
 
 
 
 
 
 
 
 
 
7.7 
Subgroups  
There is no prespecified subgroup analysis for this study. Subgroup analysis may be 
conducted as needed. 


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7.8 
Standard Calculations  
 
  
 
 
 
  
 
 
 
  
 
  
 
 
 
 
 
 
  
 
 
8. 
STATISTICAL METHODS 
All statistical analyses will be performed using SAS® for Windows, version 9.4 or later. 
All data collected during this study will be presented in subject data listings.  
 
 
 


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8.1 Summarizing Disposition and Baseline Data  
8.1.1 Subject Disposition and Withdrawals 
There will be a detailed accounting of all subjects who sign an informed consent to 
participate in this trial. The following will be summarized by treatment group:   
 
 
 
 
 
 
 
  
 
 
 
  
 
 
   
 
 
 
   
8.1.2 Protocol Deviations 
Protocol deviations for all randomized subjects will be listed as by-subject listing and 
summarized descriptively.  
8.1.3 Demographics and Baseline Characteristics 
Demographics and baseline characteristics (including age, race, gender, weight, height, 
BMI, BSA, disease characteristics etc.) will be presented as by-subject listing and 
summarized by treatment group for the Safety population. See Section 7.1 for baseline 
definition. 
8.1.4 Medical History 
Medical history results will be provided as by-subject listings.  
8.1.5 Prior and Concomitant Medications 
Prior medication is defined as any medications with an end date prior to the first treatment 
date. 
All prior and concomitant medications recorded in the case report form will be listed and 
coded to matching Anatomic Therapeutic Classification codes using the most recent 
version of WHO Drug dictionary, and summarized by treatment group and by the number 
and percentage of subjects taking each medication for the Safety population.  






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8.3.3 Vital Signs 
Vital sign assessments are performed in order to characterize basic body function. The 
parameters collected in this study are: total body surface area (BSA), systolic BP (mmHg), 
diastolic BP (mmHg), temperature (0C), heart rate (bpm), respiratory rate (bpm).  All vital 
sign results will be listed as by-subject listing. 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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8.3.4 Electrocardiogram (ECGs) 
The ECG parameters include ventricular rate (beats per minute), PR interval (msec), QRS 
interval (msec), QT interval (msec), and QTc interval (msec). All ECG results will be listed 
as by-subject listing. 
  
 
 
 
 
 
 
 
 
 
   
 
 
  
 
 
 
 
  
 
 


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8.3.5 Urine Pregnancy Test 
All data from Urine Pregnancy test will be presented as a by-subject listing.  
8.3.6 Physical Exam 
All data from physical exam will be presented as a by-subject listing.  
8.3.7 Application Site Reaction Assessments  
All data from Application Site Reaction Assessments will be presented as a by-subject 
listing and/or summarized.  
 
 
 
 
 
  
 
 










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10.2 Planned Summary Tables  
 
 
 
 
 
  
  
  
 
  
 
 
 
 
 
 


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11. 
REFERENCES 
1. ASA Ethical Guidelines for Statistical Practice (2016) 
2. The Royal Statistical Society: Code of Conduct (2014) 
3. ICH Guidance on the Structure and Content of Clinical Study Reports (ICH E3, 1996) 
4. ICH Guidance on the Structure and Content of Clinical Study Reports (ICH E3(R1), 
2013) 
5. ICH Guidance on the Statistical Principles for Clinical Trials (ICH E9, 1998) 
6. ICH Guidance on the Statistical Principles for Clinical Trials (ICH E9(R1), 2017) 
 
 
 


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12. 
VERSION HISTORY  
This is the first final version of this document.