Conditions: Atopic Dermatitis
Keywords: Mild Atopic Dermatitis Moderate Atopic Dermatitis Severe Atopic Dermatitis Mild Eczema Moderate Eczema Severe Eczema
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 287
Healthy volunteers: no

Brief summary:
This is an Open-Label Extension (OLE) study to evaluate the long-term safety, tolerability, and efficacy of EDP1815 in participants with mild, moderate, and severe atopic dermatitis who have completed the treatment period of a prior clinical study ("parent study") with EDP1815.

The current parent study of this protocol is the EDP1815-207 study; A Phase 2, Multicenter, Double-Blind, Placebo-Controlled, Multiple-Cohort Study Investigating the Effect of EDP1815 in Participants for the Treatment of Mild, Moderate and Severe Atopic Dermatitis.

Detailed description:
Atopic dermatitis (atopic eczema) is a very common type of skin disease. It typically causes red, dry, and itchy skin and may have a significant impact on quality of life. Rashes may appear on the arms and behind the knees, or anywhere else on the body. While there are existing therapies, there is currently no cure for atopic dermatitis.

This study is an Open Label Extension (OLE) study to the first parent study; i.e., the EDP1815-207 study (NCT05121480). The total number of participants will be dependent on the number of participants who elect and are eligible to participate in the Open Label Extension study following participation in EDP1815-207.

All participants in this study will be treated with EDP1815, regardless of the treatment assignment in the EDP1815-207 study. There will be no placebo drug administered in this study. To minimize bias, during dosing in EDP1815-208, investigators and participants will continue to be blinded to participants' treatment allocation in the parent study whilst it is ongoing. Participants in this study will be treated with EDP1815 for up to 36 weeks, followed by a follow-up visit at approximately 4 weeks after the end of treatment.

The maximum study duration is up to 40 weeks for all participants. The participants may move directly from the parent study into the open label treatment phase without a break in study treatment, or within 7 days of completing the treatment period of the parent study. If the participants move directly into this study without a break in treatment from the parent study, the Day -1 visit should be performed at the same time as the end of treatment visit of the parent study.

The primary endpoint of safety and tolerability will be measured using the incidence and rate per 100 patient-years of treatment-emergent adverse events during the 36-week treatment period and the 4-week follow-up period of this study; and during the treatment period of this study and the parent study. TEAEs will be defined as all events starting after first dose of study drug, and on or before 28 days after last dose for each participant. All TEAEs will be included in the assessments of incidences and rates, regardless of compliance with study medication, use of other medications or deviations from the study protocol.

The secondary endpoint of efficacy will be measured using the Eczema Area and Severity Index (EASI) Score. Additionally, the Investigator's Global Assessment (IGA), percentage of Body Surface Area (BSA), Product of the IGA and BSA (IGA\*BSA), the SCORing Atopic Dermatitis (SCORAD), the Dermatology Life Quality Index (DLQI), the Peak Pruritus Numerical Rating Scale (PP-NRS), the Sleep Disturbance Numerical Rating Scale (SD-NRS), the Patient Oriented Eczema Measure (POEM) and the Atopic Dermatitis Control Tool (ADCT) will also be measured throughout the study. The number of courses of treatment with rescue therapies; and with antibiotic treatment due to skin infection, per participant, will also be measured.

Arms:
arm 1: EDP1815-207 Cohort 1 participants will receive 1.6x10\^11 total cells of EDP1815 in EDP1815-208 administered as 2 capsules once daily. (Group 1) arm 2: EDP1815-207 Cohort 2 participants will receive 6.4x10\^11 total cells of EDP1815 in EDP1815-208 administered as 2 capsules once daily. (Group 2) arm 3: EDP1815-207 Cohort 4 participants will receive 8.0x10\^10 total cells of EDP1815 in EDP1815-208 administered as 1 capsule once daily. (Group 3)

Interventions: intervention 1: EDP1815
Intervention descriptions: intervention 1: EDP1815 is an orally administered, pharmaceutical preparation of a single strain of bacteria

Protocol document:
Prot_000.pdf: 
 
 
CLINICAL STUDY PROTOCOL 
 
 
NCT05439941 
 
 
A LONG-TERM EXTENSION TRIAL IN PARTICIPANTS WITH 
ATOPIC DERMATITIS WHO PARTICIPATED IN PREVIOUS 
PHASE 2 AND 3 EDP1815 TRIALS 
 
PROTOCOL EDP1815-208 
Version 4.0 / 16 MAY 2022 


EDP1815-208  
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PROTOCOL EDP1815-208 
A LONG-TERM EXTENSION TRIAL IN PARTICIPANTS WITH 
ATOPIC DERMATITIS WHO PARTICIPATED IN PREVIOUS 
PHASE 2 AND 3 EDP1815 TRIALS  
EudraCT Number: 2022-000284-48  
IND Number: 27698 
Sponsor 
EVELO Biosciences, Inc. 
620 Memorial Drive, 5th Floor 
Cambridge, MA, 02139 
USA 
Protocol/Amendment number 
Date 
Type of 
amendment 
Protocol 4.0 
 16 May 2022 
 Global  
 
 


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STUDY CONTACT INFORMATION 
Sponsor 
EVELO Biosciences, Inc. 
Cambridge, MA, 02139 
USA 
Chief/Coordinating Investigator 
 
 
 
 
 
 
 
 
 
 
Sponsor Study Physician 
 
 
 
  
 
 
 
 
Clinical Project Manager 
 
 
 
  
 
 
 
 




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Table of Contents 
LIST OF ABBREVIATIONS .................................................................................................... 9 
PROTOCOL SUMMARY ....................................................................................................... 11 
1. 
INTRODUCTION ........................................................................................................... 13 
1.1. Atopic Dermatitis ............................................................................................................. 13 
1.2. Previous Experience with EDP1815 and Rationale for Treating Atopic Dermatitis ....... 14 
2. 
STUDY OBJECTIVE(S) ................................................................................................. 17 
2.1. Primary Objectives ........................................................................................................... 17 
2.2. Secondary Objectives ....................................................................................................... 17 
2.3. Exploratory Objectives .................................................................................................... 17 
3. 
STUDY VARIABLES ..................................................................................................... 17 
3.1. Safety Variable(s) ............................................................................................................ 17 
3.1.1. 
Primary Safety Variable(s) .................................................................................. 17 
3.1.2. 
Secondary Efficacy Variable(s) ........................................................................... 18 
3.1.3. 
Exploratory Variables .......................................................................................... 19 
3.2. Pharmacokinetic and Pharmacodynamic Variable(s) ...................................................... 20 
3.3. Safety Variables ............................................................................................................... 20 
4. 
STUDY DESIGN ............................................................................................................. 21 
4.1. Study Description ............................................................................................................. 21 
4.2. Study Duration per Participant ......................................................................................... 21 
4.3. Planned Number of Participants ...................................................................................... 21 
4.4. Anticipated Regions and Countries ................................................................................. 21 
4.5. Schedule of Study Assessments ....................................................................................... 22 
4.6. Schematic Study Diagram ................................................................................................ 26 
4.7. Rationale for study design and selection of dose ............................................................. 27 
4.7.1. 
Dose Rationale ..................................................................................................... 27 
5. 
SELECTION AND WITHDRAWAL OF PARTICIPANTS .......................................... 28 
5.1. Inclusion criteria .............................................................................................................. 28 
5.2. Exclusion criteria ............................................................................................................. 29 
5.3. Screen Failures ................................................................................................................. 29 
5.4. Discontinuation from Treatment and/or Withdrawal ....................................................... 29 
5.4.1. 
Withdrawal from the Study ................................................................................. 31 
5.4.2. 
Lost to Follow-Up ................................................................................................ 31 
6. 
STUDY TREATMENT(S) .............................................................................................. 33 
6.1. Investigational Medicinal Product(s) ............................................................................... 33 
6.2. Investigational Medicinal Product(s) to be Administered ............................................... 33 
6.3. Packaging ......................................................................................................................... 34 
6.4. Labeling ........................................................................................................................... 34 


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6.5. Handling and Storage Requirements................................................................................ 34 
6.6. IMP Accountability .......................................................................................................... 35 
6.6.1. 
eDiary .................................................................................................................. 35 
6.7. Drug Compliance ............................................................................................................. 36 
6.8. Dose Modification ........................................................................................................... 36 
6.9. Concomitant Medications and Treatments ...................................................................... 36 
6.9.1. 
Permitted Concomitant Medications and Treatments .......................................... 37 
6.9.1.1. 
Background Therapy ................................................................................. 37 
6.9.1.2. 
Rescue Therapy ......................................................................................... 37 
6.9.2. 
Prohibited Concomitant Medications and Treatments ........................................ 38 
6.9.2.1. 
Prohibited Concomitant Medications ........................................................ 38 
6.9.3. 
Immunizations ..................................................................................................... 39 
6.10. 
Blinding.................................................................................................................. 39 
7. 
STUDY PROCEDURES BY VISIT ............................................................................... 40 
7.1. Day -1 Visit ...................................................................................................................... 40 
7.2. Treatment Period (Week 4 – Week 36) ........................................................................... 41 
7.3. Week 40 Follow Up/ End of Study Visit ......................................................................... 42 
7.4. Early Termination Visit ................................................................................................... 42 
7.5. Unscheduled Visits .......................................................................................................... 42 
7.6. COVID-19 Pandemic ....................................................................................................... 43 
7.6.1. 
EDP1815 and Risk of COVID-19 Infection ........................................................ 43 
7.6.2. 
EDP1815 and COVID-19 Vaccination ................................................................ 43 
7.6.3. 
EDP1815-208 and COVID-19 Infection ............................................................. 43 
7.6.4. 
COVID-19 Mitigation Steps ................................................................................ 43 
7.7. Missed Visits and Procedures .......................................................................................... 44 
8. 
EFFICACY ASSESSMENTS ......................................................................................... 45 
8.1. Eczema Area and Severity Index ..................................................................................... 45 
8.2. Validated Investigator’s Global Assessment ................................................................... 45 
8.3. SCORing Atopic Dermatitis ............................................................................................ 45 
8.4. Patient Oriented Eczema Measure ................................................................................... 45 
8.5. Dermatology Life Quality Index ...................................................................................... 46 
8.6. Peak Pruritus Numerical Rating Scale (PP-NRS) ............................................................ 46 
8.7. Sleep Disturbance Numerical Rating Scale (SD-NRS) ................................................... 46 
8.8. Body Surface Area ........................................................................................................... 46 
8.9. Atopic Dermatitis Control Tool ....................................................................................... 46 
9. 
SAFETY ASSESSMENTS .............................................................................................. 47 
9.1. Adverse Events ................................................................................................................ 47 
9.1.1. 
Adverse Events of Special Interest ...................................................................... 47 


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9.2. Adverse Drug Reactions .................................................................................................. 47 
9.3. Serious Adverse Events ................................................................................................... 47 
9.4. Reporting and Recording AEs ......................................................................................... 48 
9.4.1. 
Assessment of AEs .............................................................................................. 49 
9.4.2. 
Assessment of Severity ........................................................................................ 49 
9.4.3. 
Assessment of Causality ...................................................................................... 50 
9.4.4. 
Description of Adverse Events ............................................................................ 50 
9.5. Reporting Serious Adverse Events .................................................................................. 50 
9.5.5. 
Follow Up of Adverse Events .............................................................................. 51 
9.6. Pregnancy ......................................................................................................................... 51 
9.7. Overdose .......................................................................................................................... 51 
9.8. Safety Signal Detection .................................................................................................... 52 
9.9. Study Halting Criteria ...................................................................................................... 52 
9.10. 
Laboratory Measurements ..................................................................................... 53 
9.10.1. 
Review of Laboratory Measurements .................................................................. 53 
9.10.2. 
Blood Volumes .................................................................................................... 54 
9.11. 
Biomarkers ............................................................................................................. 54 
9.11.1. 
Immune Protein Biomarkers ................................................................................ 54 
9.11.2. 
Transcription Analysis ......................................................................................... 54 
9.12. 
Other Safety Measurements ................................................................................... 54 
9.12.3. 
Vital Signs, Height and Weight ........................................................................... 54 
9.12.4. 
Physical Examination .......................................................................................... 55 
9.12.5. 
12-Lead Electrocardiogram ................................................................................. 55 
9.13. 
Non-Safety Measurements ..................................................................................... 55 
9.13.1. 
Digital Photography ............................................................................................. 55 
10. STUDY MANAGEMENT AND ADMINISTRATION ................................................. 56 
10.1. 
Adherence to protocol ............................................................................................ 56 
10.2. 
Monitoring ............................................................................................................. 56 
10.2.1. 
Definition of Source Data .................................................................................... 56 
10.2.2. 
Source Data Verification ..................................................................................... 57 
10.3. 
Data Management .................................................................................................. 57 
10.3.1. 
Data Quality Assurance ....................................................................................... 57 
10.3.2. 
Case Report Form Completion ............................................................................ 58 
10.3.3. 
Data Entry and Reconciliation ............................................................................. 58 
10.3.4. 
Participant Enrollment Log/Participant Identification Code List ........................ 58 
10.4. 
Termination of the Study ....................................................................................... 58 
10.5. 
Archiving and Data Retention ............................................................................... 59 
10.6. 
Audit and Inspection .............................................................................................. 59 


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10.7. 
Good Clinical Practice ........................................................................................... 59 
11. STATISTICS ................................................................................................................... 60 
11.1. 
General Statistical Considerations ......................................................................... 60 
11.2. 
Definition of Analysis Sets and Defined Data Point Sets ...................................... 60 
11.2.1. 
Participant Analysis Sets ..................................................................................... 60 
11.2.2. 
Defined Data Point Sets ....................................................................................... 60 
11.3. 
Estimands and Intercurrent Events ........................................................................ 61 
11.3.1. 
Primary Estimand of the Primary Objective ........................................................ 62 
11.3.2. 
Secondary Efficacy Estimands ............................................................................ 63 
11.3.3. 
Exploratory Estimands ......................................................................................... 65 
11.3.4. 
Safety Estimands ................................................................................................. 67 
11.4. 
Planned Analyses ................................................................................................... 67 
11.5. 
Handling of Protocol Deviations ........................................................................... 67 
11.6. 
Handling of Dropouts or Missing Data .................................................................. 67 
11.7. 
Planned Interim Analysis and Data Monitoring .................................................... 67 
11.8. 
Determination of Sample Size ............................................................................... 68 
12. ETHICS AND REGULATORY REQUIREMENTS ...................................................... 69 
12.1. 
Informed Consent................................................................................................... 69 
12.2. 
Participant Identification Cards ............................................................................. 69 
12.3. 
Institutional Review Boards and Independent Ethics Committees ........................ 69 
12.4. 
Participant Privacy ................................................................................................. 70 
12.5. 
Protocol Amendments ............................................................................................ 71 
12.6. 
Insurance ................................................................................................................ 71 
12.7. 
Financial Disclosures ............................................................................................. 71 
12.8. 
Publications ............................................................................................................ 71 
12.8.1. 
Dissemination of Clinical Study Data ................................................................. 71 
13. REFERENCES ................................................................................................................ 72 
14. APPENDICES ................................................................................................................. 75 
14.1. 
Classification of Potency of Topical Corticosteroids ............................................ 75 
14.2. 
Contraceptive Guidance and Collection of Pregnancy Information ...................... 76 
14.3. 
EDP1815 COVID-19 Risk Assessment ................................................................. 79 
14.4. 
Toxicity Grading Scale .......................................................................................... 84 
15. DECLARATION AND SIGNATURE OF INVESTIGATOR ....................................... 86 
16. SPONSOR DECLARATION .......................................................................................... 87 
17. PROTOCOL AMENDMENTS ....................................................................................... 88 
 
LIST OF TABLES 
Table 4-1: Schedule of Assessments........................................................................................ 22 


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Table 6-1: IMP to be Administered ......................................................................................... 34 
Table 11-1: Secondary Efficacy Estimands ............................................................................. 65 
Table 11-2: Exploratory Estimand Details .............................................................................. 65 
Table 11-3: Safety Estimand Details ....................................................................................... 67 
Table 14-1: 
Highly Effective Contraceptive Methods ........................................................ 77 
 
LIST OF FIGURES 
Figure 4-1: Schematic Diagram ............................................................................................... 26 
 
 
 
 
 


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LIST OF ABBREVIATIONS 
AD 
Atopic Dermatitis 
ADCT 
Atopic Dermatitis Control Tool 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
APP 
Application 
AST 
Aspartate Aminotransferase 
BSA 
Body Surface Area 
CDMS 
Clinical Data Management System 
CI 
Confidence Intervals 
CPM 
Clinical Project Manager 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DLQI 
Dermatology Life Quality Index 
DNA 
Deoxyribonucleic Acid 
DPS 
Data Point Set 
EC 
Enteric Coating 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EMA/EMEA 
European Medicines Agency 
EASI 
Eczema Area and Severity Index 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIV 
Human Immunodeficiency Virus 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IGA 
Investigator Global Assessment 


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IgE 
Immunoglobulin E 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
LS 
Least Squares Mean Estimate 
mL 
Milliliter 
OLE 
Open Label Extension 
PP-NRS 
Peak Pruritus Numerical Rating Scale 
RNA 
Ribonucleic Acid 
SD-NRS 
Sleep Disturbance Numerical Rating Scale 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SLS 
Sodium Lauryl Sulfate 
SOP 
Standard Operating Procedure 
TCPD-1815 
Total Cells per Day of EDP1815 
TEAE 
Treatment Emergent Adverse Event 
TMF 
Trial Master File 
WOCBP 
Woman of Child-Bearing Potential 


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PROTOCOL SUMMARY 
 
Study Objectives:  
 
The primary objective of the study is to: 
 
• Evaluate the long-term safety and tolerability of EDP1815 in the treatment of atopic 
dermatitis. 
 
The secondary objective of the study is to: 
 
• Evaluate the efficacy of long-term treatment with EDP1815 in the treatment of atopic 
dermatitis.  
 
Primary endpoint: The incidence and rate per 100 patient-years of treatment emergent adverse 
events (TEAEs) during the 36-week treatment and 4-week follow-up period. 
 
Secondary endpoints:  The Eczema Area and Severity Index (EASI) Score will be utilized to 
measure the efficacy of EDP1815 in the treatment of atopic dermatitis.  In addition to EASI, the 
Investigator’s Global Assessment (IGA), percentage of Body Surface Area (BSA), Product of the 
IGA and BSA (IGA*BSA), the SCORing Atopic Dermatitis (SCORAD), the Dermatology Life 
Quality Index (DLQI), the Peak Pruritus Numerical Rating Scale (PP-NRS), the Sleep Disturbance 
Numerical Rating Scale (SD-NRS), the Patient Oriented Eczema Measure (POEM) and the Atopic 
Dermatitis Control Tool (ADCT) will be measured throughout the study.  
 
The number of courses of treatment with rescue therapies; and with antibiotic treatment due to 
skin infection, per participant, will also be measured.  
 
Brief Study Design: This is an Open-Label Extension (OLE) study to evaluate the long-term 
safety, tolerability, and efficacy of EDP1815 in participants with mild, moderate, and severe atopic 
dermatitis who have completed the treatment period of a prior clinical study (“parent study”) with 
EDP1815. The parent study of this open label extension protocol is the EDP1815-207 study; A 
Phase 2, Multicenter, Double-Blind, Placebo-Controlled, Multiple-Cohort Study Investigating the 
Effect of EDP1815 in Participants for the Treatment of Mild, Moderate and Severe Atopic 
Dermatitis. The EDP1815-207 study will be referenced as the parent study throughout the protocol.  
 
This study may serve as an open label extension study for future EDP1815 studies in Atopic 
Dermatitis.  
 
All participants in this study will be treated with EDP1815, regardless of the treatment assignment 
in the EDP1815-207 study. To minimize bias, during dosing in EDP1815-208, investigators and 
participants will continue to be blinded to participants’ treatment allocation in the parent study 
whilst it is ongoing. Participants in this study will be treated with EDP1815 for up to 36 weeks, 
followed by a follow-up visit at approximately 4 weeks after the end of treatment. 
 


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Interim safety and efficacy analyses may be performed throughout the study as required for 
ongoing evaluation of the benefit-risk profile for EDP1815. These may include either all 
participants enrolled in the study or use of a subset of participants who transitioned to this study 
from a specific parent study. Interim analyses may also incorporate data collected within the parent 
Atopic Dermatitis EDP1815 studies which feed into this study. 
 
Study Duration: The maximum study duration is up to 40 weeks for all participants, which will 
include a 36-week treatment period and a 4-week post treatment follow-up period. The participants 
may move directly from the parent study into the open label treatment phase without a break in 
study treatment, or within 7 days of completing the treatment period of the parent study. If the 
participants move directly into this study without a break in treatment from the parent study, the 
Day -1 visit should be performed at the same time as the end of treatment visit of the parent study.  
 
  
 
 
 
 


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1. INTRODUCTION 
 
1.1. 
Atopic Dermatitis 
Atopic dermatitis (AD), also known as (atopic) eczema, is a chronic, highly symptomatic relapsing 
inflammatory skin disease, affecting up to 30% of children and 10% of adults (Bieber, Atopic 
Dermatitis, 2010).  While AD often begins in infancy or childhood, it may become chronic and 
persist into adulthood (Katoh, 2019). Depending on factors such as severity of skin lesions or body 
surface area coverage, the disease can be classified clinically as mild, moderate, or severe. 
 
Patients with AD typically have highly symptomatic skin lesions that may present acutely with 
erythema, exudates, papulovesicles, scales and crusts, often symmetrically distributed on the body 
(Katoh, 2019).  The disease typically follows a variable course with acute flares, often triggered 
by external factors, which cause a worsening of skin disease and symptoms. More chronic lesions 
are associated with thickened lichenified skin which may be accompanied by pigmentary changes 
and further excoriations (Bieber, Atopic Dermatitis, 2010). The primary symptom at both stages 
of disease is typically pruritus (itch). Such signs and symptoms are associated with a substantial 
patient burden that typically includes sleep disturbance, mood disturbance mental health problems 
(Simpson, 2012), poor quality of life and social functioning (Kiebert, 2002). 
 
AD, like other atopic disease, is characterized by a T helper type 2 (Th2) cell-mediated 
inflammation, with up-regulation of Th2 cytokines including IL-4, IL-5, and IL-13 (Indra, 2013). 
In turn, this leads to increased IgE production by B-cells, which can trigger release of cytokines 
and chemical mediators such as histamine from mast cells and Langerhans cells. In addition, 
thymic stromal lymphoprotein is thought to be a critical cytokine in the triggering and maintenance 
of AD (Indra, 2013), and is associated with migration of Th2 cells into the skin lesion (Katoh, 
2019). The resulting systemic inflammation drives the disease pathology and patient symptoms, 
with the resultant scratching of pruritic lesions further worsening the skin lesions and the skin 
barrier function, further driving the disease process. Therefore, targeting systemic inflammation 
improves disease signs and symptoms – for example systemic corticosteroids typically lead to 
rapid clinical improvements, but generally are not acceptable as a long-term treatment due to 
associated side-effects (Lee, 2016). 
 
In general, treatment of AD is aimed at a combination of resolution of skin disease and 
improvement of symptoms such as itch (acute therapy), and also prevention of further flares 
(maintenance therapy). Emollients, also known as moisturizers, are the first-line and baseline 
therapy for all severities of disease, and act by treating the defective skin barrier and providing 
cutaneous hydration (Lee, 2016). There are a number of other topical treatments including topical 
corticosteroids (TCS) and topical calcineurin inhibitors (TCI) (Katoh, 2019). Newer topical 
therapies for AD include Janus Kinase (JAK) and Phosphodiesterase 4 (PDE) inhibitors (Bieber, 
2021). Unfortunately, there are associated issues with such current treatments including adverse 
effects, limitations in efficacy, and low patient acceptability and tolerability, particularly when 
used as chronic treatment options. 
 
There are currently no licensed oral treatments for mild to moderate atopic dermatitis. There are 
currently two classes of oral medications approved for the treatment of moderate to severe atopic 
dermatitis; Ciclosporin (approved in the European Union (EU)) and JAK Inhibitors (newly 


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approved in the EU & US). Due to its associated risks and side-effects, such as renal failure, 
ciclosporin is generally only recommended for short-term use (Katoh, 2019). The most common 
serious adverse reactions associated with JAK inhibitors are infections, others include nausea, 
headache, and acne. Other anti-inflammatory treatments, such as methotrexate or azathioprine, are 
therefore used off license in order to reduce the Th2-driven systemic inflammation. These systemic 
treatments all have associated risks and side-effects and are therefore not suitable for a large 
population of patients, including many of those with mild and moderate disease. Finally, for 
patients with moderate-to-severe disease dupilumab and tralokinumab are now licensed as a 
biologic injectable treatment and are currently used to treat a small proportion of patients with 
such disease severity. 
 
A 2016 patient survey (National Eczema Association, 2016) highlights and summarizes what it is 
like for patient living with atopic dermatitis: 
• 84% are “very” or “extremely” bothered by dry skin, 83% by itch, and 63% by rash/redness 
• 75% stated AD interferes with their job and house chores, 71% say it interferes with 
hobbies, and 65% don’t feel as healthy because of AD 
• Nearly half of people with moderate to severe AD report their disease “interferes with their 
social life, intimate relations, and relationships with their spouse and children” 
• 1 in 3 takes one or more hours per day to treat their AD 
• More than half are dissatisfied overall with each of the following treatments that they are 
using or have used: topical steroids, topical calcineurin inhibitors, phototherapy, and oral 
medications 
 
The conclusion from this study was that there is a “lack of safe and effective treatments” for AD, 
allowing for “unchecked symptoms [which] contribute to the range of health issues”. This sums 
up the unmet need for and importance of further oral treatments for AD. 
 
1.2. 
Previous Experience with EDP1815 and Rationale for Treating Atopic 
Dermatitis 
 
Evelo Biosciences, Inc. (Evelo) is developing orally administered biologic medicines based on a 
new understanding of how immunity and inflammation are controlled. Evelo’s experimental 
medicines are selected for their ability to modulate the small intestinal axis (SINTAX™). This is 
the network of anatomical and functional connections that has evolved to link the small intestine 
and the rest of the body. It links small intestinal mucosal immunology with systemic inflammation 
and is accessible with oral SINTAX medicines. 
 
The inflammatory control mechanisms of SINTAX down-regulate multiple inflammatory 
pathways including those which have been validated with targeted antibody therapies, but without 
the side effects seen with antibody therapeutics or broadly acting oral kinase inhibitors. This occurs 
via specific interactions between the oral SINTAX therapy and small intestine enterocytes and 
immune cells. These interactions drive the development of an immune-regulatory subset of 
lymphocytes that travel from the gut to the systemic circulation, via the mesenteric lymph nodes. 
Here, these circulating cells mediate their effects on peripheral inflammation at the target sites 
(e.g., atopic dermatitis skin). 
 


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EDP1815 is a pharmaceutical preparation of a single strain of Prevotella histicola, originally 
isolated from a duodenal biopsy. The drug substance is essentially non-viable and non-replicating, 
with a cell viability of <0.02%. It has not been genetically modified. It does not colonize the gut 
nor alter the microbiome and has no detectable systemic exposure following oral dosing to date – 
i.e., it is gut-restricted. 
 
Prevotella as a genus are gram-negative, obligate anaerobic bacteria that are natural human 
commensals found in the oral cavity and gastrointestinal (GI) tract. Strains of Prevotella have been 
found in all human populations tested to date, at abundances ranging from <1% to nearly 50% of 
total fecal microbial load (Vandeputte, Kathagen, & D'hoe, 2017). 
 
In vitro studies of EDP1815 in human and mouse cellular assays and in vivo models support its 
use in the treatment of immunoinflammatory diseases, including atopic dermatitis. Oral 
administration of EDP1815 to mice led to striking therapeutic effects on delayed-type 
hypersensitivity (DTH), imiquimod-induced skin inflammation, fluorescein isothiocyanate (FITC) 
cutaneous hypersensitivity, collagen-induced arthritis (CIA) (Marietta, Murray, & Luckey, 2016) 
and experimental acute encephalomyelitis (EAE) (Mangalam, Shahi, & Luckey, 017) in-vivo 
models. EDP1815 was shown to down-regulate key Th2-related cytokines including IL-4 and IL-
31. No potentially related adverse effects were seen in the animals used in these experiments with 
daily dosing for up to 3 weeks, or alternate day dosing for over 7 weeks. Ex vivo 
immunophenotyping in these models shows increased regulatory T cell numbers and regulatory 
dendritic cells (DCs) in spleen and mesenteric lymph nodes, as well as decreases in pro-
inflammatory cytokines such as IL-23 p40, IL-17, and IL-13. EDP1815 does not suppress the 
expression of Type-1 interferons in these ex vivo experiments, suggesting that the broad spectrum 
of anti-inflammatory effects is achieved without damaging mechanisms of immune surveillance 
critical for avoiding cancers and pathogens. Treatment also led to enhancement of gut intestinal 
barrier integrity, which is often disrupted in patients with inflammatory diseases. The effects on 
immune parameters have been observed both within and outside of the GI tract, which 
demonstrates that host-microbe interactions in the gut can affect the immune response in peripheral 
tissues.  
 
This pre-clinical data therefore supported advancing EDP1815 into the treatment of atopic 
dermatitis, due to the resolution of systemic inflammation including in models of Th2-driven 
disease, and the reduction of Th2-dervied cytokines that are known to drive the pathophysiology 
of atopic dermatitis. 
 
Clinical data is accumulating that supports both the role of the small intestinal axis in humans and 
that it can be harnessed by EDP1815 as a potent modulator of systemic inflammation, in Th1, Th2 
and Th17 inflammation. As of January 2022, a total of 458 adult participants have been exposed 
to EDP1815 in the phase 1 and 2 studies. The breakdown is as follows: phase 1 studies: 134 
participants in EDP1815-101 (complete) and 24 healthy volunteers in EDP1815-102 (complete) 
and12 participants in EDP1815-104 (ongoing). In Phase 2 studies, approximately 166 participants 
have been exposed to EDP1815 for up to 16 weeks in duration in the EDP1815-201 Psoriasis study 
(complete), 8 participants in the EDP1815-205 COVID-19 study (complete) and 114 participants 
in TATIC-E (complete). To date, EDP1815 is well tolerated with a safety profile comparable to 
placebo and there are no AEs of special interest.  


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In the Phase 1b study (EDP1815-101), 16 participants with mild or moderate atopic dermatitis in 
cohort 7 were treated with EDP1815 capsules at a dose of 8.0 x 1011 cells once daily for 8 weeks, 
with a further 8 participants given matching placebo. Clinically meaningful and significant 
responses were observed at the end of the treatment period, in terms of the changes in EASI, 
IGA*BSA and SCORAD, as well as within the patient-reported outcomes, which also found 
improvements in itch and sleep scores. A further 16 participants were treated with EDP1815 daily 
for 8 weeks at a capsule dose of 6.4 x 1011 total cells, with another 8 participants on placebo in 
cohort 10 of this study. In this cohort, EDP1815 was shown to be well-tolerated with no treatment-
related adverse events of moderate or severe intensity and no serious adverse events through eight 
weeks of dosing.  The above efficacy was not clearly replicated in this small cohort, although the 
primary endpoint of safety and tolerability was. The safety profile was consistent with that seen in 
other studies of EDP1815.  
 
The available evidence to date has found EDP1815 to be well tolerated with evidence for proof of 
concept as a potential effective treatment for atopic dermatitis. A well tolerated oral therapy could 
offer significant benefit in atopic dermatitis for all severities of disease.  
 


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2. STUDY OBJECTIVE(S) 
 
2.1. 
Primary Objectives 
The primary study objective is to evaluate the long-term safety and tolerability of EDP1815 in the 
treatment of atopic dermatitis The primary endpoints to measure this objective will be the 
incidence and rate per 100 patient-years of treatment-emergent adverse events during the 36-week 
treatment period and the 4-week follow-up period of this study, and during the treatment period of 
this study and the relevant parent study. 
 
TEAEs will be defined as all events starting after first dose of study drug and on or before 28 days 
after last dose for each participant.  All TEAEs will be included in the assessments of incidences 
and rates, regardless of compliance with study medication, use of other medications or deviations 
from the study protocol. 
 
2.2. 
Secondary Objectives 
The secondary objective of this study is to evaluate the efficacy of long-term treatment with 
EDP1815 in the treatment of atopic dermatitis 
 
2.3. 
Exploratory Objectives 
The exploratory objectives of this study are the following:  
 
1. To evaluate the time to onset of clinical response to EDP1815. 
 
2. To evaluate other aspects of the efficacy of EDP1815 as a treatment for atopic dermatitis 
 
3. To evaluate the relationship of EDP1815 treatment with biomarkers such as immune 
protein markers and immune cell RNA profile in blood. 
 
 
3. STUDY VARIABLES 
 
3.1. 
Safety Variable(s) 
3.1.1. 
Primary Safety Variable(s) 
 
The primary safety variables will be the incidence and rate per 100 patient-years of TEAEs. Both 
the period defined by this study alone and the period defined by this study and the relevant 
parent study will be reported. 
 
Subgroups of TEAEs will be evaluated as follows: 
• All TEAEs 
• TEAEs of Grade 2 or above 
• TEAEs of Grade 3 or above 
• Serious TEAEs 
• Fatal TEAEs 
• TEAEs causing discontinuation of study drug 


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• Study drug related TEAEs Study (defined by an investigator assessment of possible, 
probable, or definite relationship to IMP) 
• Study drug related TEAEs of Grade 2 or above 
• Study drug related TEAEs of Grade 3 or above 
• Study drug related serious TEAEs 
• Study drug related fatal TEAEs 
• Study drug related TEAEs causing discontinuation of study drug 
 
 
3.1.2. 
Secondary Efficacy Variable(s) 
The following secondary endpoints will be evaluated at all scheduled visits to evaluate the 
maximum efficacy of EDP1815 in the treatment of atopic dermatitis. For all measures involving 
changes from baseline, the baseline assessment from the relevant EDP1815 parent study will be 
used. 
 
• Percentage of participants achieving EASI-50  
• Percentage of participants achieving EASI-75  
• Percentage of participants achieving EASI-90  
• Mean absolute change and percentage change from baseline in EASI Score  
 
• Percentage of participants achieving IGA of 0 or 1 with a ≥2 point improvement from 
baseline 
• Percentage of participants achieving IGA of 0 or 1 
• Percentage of participants achieving IGA of 0 
 
• Mean absolute change and percentage change from baseline in IGA*BSA  
• Mean absolute change and percentage change from baseline in BSA 
• Percentage of participants achieving BSA-50 
• Percentage of participants achieving BSA-75 
• Percentage of participants achieving BSA reduction to 3% or less 
 
• Mean absolute change and percentage change from baseline in SCORAD  
• Percentage of participants achieving SCORAD-50  
• Percentage of participants achieving SCORAD-75  
 
• Mean absolute change and percentage change from baseline in DLQI  
• Percentage of participants achieving a reduction of ≥4 in the DLQI, of those with a score 
of ≥4 at baseline 
 
• Mean absolute change from baseline in PP-NRS 
• Percentage of participants achieving a reduction of ≥2 in the PP-NRS, of those with a score 
of ≥2 at baseline  
• Percentage of participants achieving a reduction of ≥4 in the PP-NRS, of those with a score 
of ≥4 at baseline  
 


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• Mean absolute change from baseline in SD-NRS 
• Percentage of participants achieving a reduction of ≥2 in the SD NRS, of those with a score 
of ≥2 at baseline  
 
• Mean absolute change and percentage change from baseline in Patient Oriented Eczema 
Measure (POEM)  
• Percentage of participants achieving a reduction of ≥4 in the POEM score, of those with a 
score of ≥4 at baseline 
  
• Number of courses per patient-year of any rescue medication (not including antibacterial 
therapy) 
• Number of courses per patient-year of topical corticosteroids of any potency 
• Number of courses per patient-year of topical tacrolimus (0.1%), topical pimecrolimus 
(1%) or grade VII topical corticosteroid 
• Number of courses per patient year of moderate potency (grade IV and V) topical steroids 
 
3.1.3. 
Exploratory Variables 
The following endpoints will be used to evaluate the time to onset of clinical response to EDP1815: 
• Time to first achievement of EASI-50 
• Time to first achievement of sustained EASI-50 (sustained EASI-50 response is defined as 
one which is present at consecutive visits spanning at least 8 weeks in the absence of rescue 
medication) 
 
The following endpoints will be used to evaluate other aspects of the efficacy of EDP1815 as a 
treatment for atopic dermatitis 
 
• Changes from baseline in ADCT scores 
• Mean absolute and percentage change in the four body region scores of the EASI 
• Percentage of participants achieving at least a 50% reduction in each of the four body 
region scores of those with a non-zero score for the relevant region at baseline 
• Percentage of participants who change response states from Day -1 to Weeks 8, 16, 24 and 
36. Response states will be defined using the EASI score percentage change from baseline 
with categories for ≥25% increase, no change (<25% increase to <25% decrease), 25% to 
<50% decrease, 50% to <75% decrease, 75% to <90% decrease, ≥90% decrease). 
• Daily mean absolute change from baseline in PP-NRS and SD-NRS scores. 
 
The following endpoints will be used to evaluate the relationship of EDP1815 treatment with 
biomarkers such as immune protein markers and immune cell RNA profile in blood. 
 
• Changes from baseline in serum immune protein markers including IgE  
• Changes from baseline in immune cell RNA profile  
 
 
 


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3.2. 
Pharmacokinetic and Pharmacodynamic Variable(s) 
EDP1815 has no systemic absorption and therefore no systemic exposure. No samples for 
pharmacokinetic analysis will be performed in this study.  
 
3.3. 
Safety Variables 
The severity and frequency of adverse events will be used to evaluate the safety and tolerability of 
EDP1815.  Vitals signs, weight, physical examinations, clinical laboratory tests, ECG and use of 
concomitant medications will also be used to evaluate the safety and tolerability of EDP1815. 
 
 


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4. STUDY DESIGN 
 
4.1. 
Study Description 
This is an Open-Label Extension, multicenter study to evaluate the long-term safety, tolerability, 
and efficacy of EDP1815 in participants with mild, moderate, and severe atopic dermatitis. 
Participants who have completed the 16-week treatment period in the EDP1815-207 parent study 
may be eligible to enroll in this study.   
 
4.2. 
Study Duration per Participant 
The total duration of participation in this study is up to a maximum of 40 weeks from Day -1 to 
follow-up.  
 
Participants will undergo: 
 
• A Day -1 Visit  
 
• A 36-week Treatment Period consisting of 6 study visits  
 
• A 4-week Post-Treatment Follow-up Visit  
 
The end of the study is defined as the date of the last visit of the last participant (LPLV). 
 
4.3. 
Planned Number of Participants 
This study will be conducted as a multi-center study. The total number of participants will be 
dependent on the number of participants who elect and are eligible to participate in the Open Label 
Extension study following participation in the EDP1815-207 parent study.  
 
4.4. 
Anticipated Regions and Countries 
This study will be conducted at centers located in North America, Europe, and Asia Pacific. 








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e  
Women of child-bearing potential only. Pregnancy testing (urine) will be performed at the visits indicated and if a menstrual cycle is missed or if 
pregnancy is otherwise suspected. 
f  
A single ECG tracing is to be obtained on the day of the visit after the participant has rested for 5 minutes in supine position. If, in the opinion of the 
Investigator, there appears to be clinically significant findings, repeat tracings should be obtained, as necessary. 
g  
Results from the laboratory assessments performed at the Day-1 visit will not be required to confirm eligibility for participation in the study. The 
investigator may use results from the parent study to confirm eligibility. 
h  
Blood pressure, heart rate, respiratory rate, and temperature will be measured after  the participant has rested for at least 5 minutes in supine position.  
i  
Study staff will assist the participant in the transition of studies within their eDiary device at the Day-1 visit. The staff will review the eDiary with 
participants at each visit. eDiaries will be reviewed for completeness and accuracy, and participants will be coached as needed on compliance with the 
protocol. 
j  
EDP1815-207 Cohort 3 participants that are confirmed as eligible to participate in this study at the Day-1 visit will be randomized 1:1 to receive either 
1.6x1011 total cells of EDP1815, or 6.4x1011 total cells of EDP1815. 
k  
Study medication will be dispensed after all Day -1 activities are completed and if the participant is confirmed as eligible to participate in the study. The 
participant will be instructed to take the first IMP dose on Day 1 at home. The capsules are to be taken once daily at approximately the same time each 
day.   On study visit days, dosing may occur at home prior to the study visit. Participants should refrain from consuming acidic drinks 1 hour either side 
of dosing and from eating 2 hours before dosing and 1 hour after dosing. Participants will be required to record their daily dosing in the eDiary.  
l  
AD Investigator rating scales. Participants will be asked to withhold all emollients, sunscreens, or moisturizers on the day of these study visits until all 
study assessments are completed. 
m  
The Pruritus-NRS (worst itch) and the Sleep Disturbance-NRS (SD-NRS) scale will be asked daily from the Day-1 Visit to the Week 40 or Early 
Termination Visit (if applicable) via the participant eDiary. 
n  
Digital photographs should be taken of the upper and lower body (upper & lower anterior and upper & lower posterior) as half body shots. Additional 
close-up photographs of up to six specific body areas (i.e., limbs, trunk and back) may also be taken. The same sites photographed in the parent study 
should be followed throughout this study for each participant. 
o  
Participants who withdraw from the study early will have an Early Termination Visit. If due to treatment failure, this visit should be arranged within 72 
hours of the start of any new AD therapy, when possible. The participant will also be asked to have a final telephone call 28 days (+3 days) after taking 
their last dose of IMP for safety assessments. The date of this telephone call will be considered the end of study date for these participants. 
p  
Adverse Events (AE) and Serious Adverse Events (SAE) will be captured from the time the participant signs the informed consent. 




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4.7. 
Rationale for study design and selection of dose 
 
4.7.1. Dose Rationale 
 The doses, and corresponding regimen selected for evaluation within this study are: 
 
• Group 1: 1.6x1011 total cells of EDP1815 administered as 2 capsules once daily.  
• Group 2: 6.4x1011 total cells of EDP1815 administered as 2 capsules once daily.  
• Group 3: 8.0x1010 total cells of EDP1815 administered as 1 capsule once daily. 
 
The doses administered in this study are the same as those administered in the EDP1815-207 
parent study.  
 
No placebo will be administered in this study. The following will apply for all EDP1815-207 
participants who transition into this study:   
 
• EDP1815-207 Cohort 1 participants will receive 1.6x1011 total cells of EDP1815 in 
EDP1815-208 (Group 1) 
• EDP1815-207 Cohort 2 participants will receive 6.4x1011 total cells of EDP1815 in 
EDP1815-208 (Group 2) 
• EDP1815-207 Cohort 3 participants will be randomized 1:1 to receive either 1.6x1011 total 
cells of EDP1815 (Group 1), or 6.4x1011 total cells of EDP1815 (Group 2) in EDP1815-
208  
• EDP1815-207 Cohort 4 participants will receive 8.0x1010 total cells of EDP1815 in 
EDP1815-208 (Group 3) 
 
The pharmacological site of action of EDP1815 is within the epithelium of the small intestine 
where EDP1815 interacts with immune and epithelial cells.  These interactions modify the 
systemic immune system and promote inflammation resolution throughout the body.  The 
preclinical and clinical data generated to date suggest this is a broad effect working across Th1, 
Th2 and Th17 pathologies.  As the intent is to generate a maximal inflammation-resolving 
phenotype regardless of inflammation pathology, the dose response is expected to be common 
across indications, and therefore we aim to cross-compare to previous studies to support this 
hypothesis.  
 
Evelo’s Phase 1 Study EDP1815-101 evaluated EDP1815 for the treatment of atopic dermatitis 
with an oral dose of 8.0x1011 cells delivered as 10 capsules once a day for 8 weeks.  This dose was 
safe and well tolerated and clinical benefit was observed with an improvement of 50-65% over 
placebo by Week 8 in EASI and vIGA*BSA endpoints, together with improvements in other 
measures such as the SCORAD. In addition, 7 out of 16 (44%) participants dosed with EDP1815 
for 8 weeks achieved an EASI-50 by day 70, compared with 0% in the placebo group. An 
additional cohort investigated a dose of 6.4 x 1011 total cells administered daily for 8 weeks. The 
above efficacy was not clearly replicated in this small cohort, although the primary endpoint of 
safety and tolerability was. Given a potential difference in clinical effects seen between the two 
cohorts which were dosed with EDP1815 produced using different manufacturing processes, the 


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Company is evaluating drug substance produced using both manufacturing processes in the 
EDP1815-207 Phase 2 Atopic Dermatitis study. 
  
A Phase 2 dose ranging study in psoriasis (EDP1815-201) was conducted in approximately 225 
participants for 16 weeks, at doses of 8.0x1010, 3.2x1011, and 8.0x1011 cells. No evidence of dose 
response was seen in this study. Further information on these studies is detailed in the EDP1815 
Investigator’s Brochure (IB).  
The doses selected for evaluation in both the EDP1815-207 parent study and subsequently this 
open label extension study represent commercially acceptable dosing regimens in terms of capsule 
load and frequency for patients. The dose of 8.0x1010 total cells and 1.6x1011 total cells are 
comparable with data being generated in the lower dose cohorts of EDP1815-201, whilst the dose 
of 6.4x1011 total cells approximates to that administered in EDP1815-101, cohort 7. 
 
5. SELECTION AND WITHDRAWAL OF PARTICIPANTS 
Participants with a confirmed diagnosis of mild, moderate, or severe atopic dermatitis will be 
treated in this study only if they meet all inclusion and no exclusion criteria. Any participant who 
signs the informed consent form will be considered enrolled in the study. Study eligibility 
procedures will begin after participants sign the informed consent.  
 
5.1. 
Inclusion criteria 
 
To be eligible to participate in this study, all the following criteria must be met: 
 
1. Must have given written informed consent (signed and dated) and any authorizations 
required by local law and be able to comply with all study requirements. 
 
2. Must have completed the treatment period in a parent study of EDP1815 in the treatment 
of atopic dermatitis and complied with the protocol to the satisfaction of the investigator 
  
3. All participants must agree to continue the use of a bland additive-free, sodium lauryl 
sulfate (SLS)-free, and fragrance-free emollient cream, gel, or ointment at least twice daily 
(or more, as needed) throughout the study. 
 
4. Continue to meet the following contraception criteria: 
i. Male participants: 
i. A male participant must agree to use contraception during their participation in this 
study and for a period of 90 days after the last dose and refrain from donating sperm 
during this period. 
ii. Female participants: 
i. A female participant is eligible to participate if she is not pregnant, not 
breastfeeding, and at least 1 of the following conditions applies: 
1. Not a WOCBP or 
2. A WOCBP who continues to follow the contraceptive guidance provided in the 
parent study during participation in this study, including (if applicable) 7 days 
prior to the first dose, and for at least 1 complete menstrual cycle (≥30 days) 
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5.2. 
Exclusion criteria 
 
Participants are not permitted to participate in this study if any of the following criteria is met: 
 
1. Participants who are currently enrolled in another investigational drug study or plans to 
receive another investigational agent during this study. 
 
2. Have any other conditions, which, in the opinion of the Investigator or Sponsor, would 
make the participant unsuitable for inclusion or could interfere with the participant 
participating in or completing the study. 
 
3. Treatment with phototherapy, a biologic agent, or a systemic immunosuppressive agent 
that could affect AD, including systemic corticosteroids, within 7 days prior to Day -1, 
unless used as a rescue treatment as part of the parent study protocol.  
 
4. Treatment with topical atopic dermatitis therapies, including topical corticosteroids, topical 
calcineurin inhibitors, topical PDE-4 inhibitors, and topical JAK inhibitors, within 7 days 
prior to Day -1, unless used as a rescue treatment as part of the EDP1815-207  protocol. 
 
5. Has received live or live-attenuated vaccination within 7 days  prior to Day -1 or intends 
to have such a vaccination during the study. Non-live and non-replicating vaccines are 
permitted. 
 
6. Hypersensitivity to P histicola or to any of the excipients. 
 
7. Unwillingness to comply with study procedures, including follow-up, as specified by this 
protocol, or unwillingness to cooperate fully with the Investigator. 
 
 
5.3. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study due to failure to meet eligibility criteria. There is no screening 
period within this study; however, if the participant fails to meet the eligibility criteria, they will 
be defined as a screen failure. A minimal set of screen failure information is required to confirm 
transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes informed consent, demography, screen failure details, 
eligibility criteria, and any AEs and SAEs.  
 
5.4. 
Discontinuation from Treatment and/or Withdrawal 
Participants may discontinue from treatment and withdraw their participation from the study at 
any time and for any reason without prejudice to their future medical care by the Investigator or at 
the study site. Every effort should be made to keep participants in the study. The reasons for 


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participants discontinuing treatment and withdrawing from the study will be recorded in the source 
files and on the eCRF.  
 
Interruption of treatment is defined as a temporary stopping of IMP that resumes during the 
treatment period, due to an AE or any other reason. The maximum permitted interruption is 14 
consecutive days. Participants should have 80% compliance with IMP administration between any 
two visits after allowing for permitted interruptions. 
 
Early discontinuation of treatment is defined as permanent stopping of IMP before the Week 36 
visit. Investigators will strive to confirm that a participant who has interrupted treatment for a 
particular reason will not discontinue IMP unless discontinuation is medically imperative in the 
Investigator’s judgment. However, a dose interruption of more than 14 consecutive days or 
multiple dose interruptions resulting in <80% compliance with IMP administration between any 
two visits may result in discontinuation of IMP and early termination of the participant.  
 
Early withdrawal from the study is defined as failing to complete the 36-week treatment and the 
follow-up visit.  
 
A participant will discontinue IMP and be withdrawn from the study for any of the following 
reasons: 
 
1. The participant experiences treatment failure, demonstrated by the participant commencing 
phototherapy, an oral agent, biological, or intermediate or high-potency topical therapy for 
atopic dermatitis, other than those permitted as rescue therapy. 
 
2. The participant has a serious or intolerable AE that in the Investigator’s opinion requires 
discontinuation from IMP and withdrawal from the study.   
 
NB: Dosing may be interrupted at the Investigator’s discretion due to AE or intercurrent 
illness for a period of up to 14 consecutive days, following which the participant may 
resume treatment if the Investigator considers it safe to do so.  The participant should 
discontinue treatment permanently if the same AE which caused dose interruption occurs a 
second time requiring another dose interruption and is believed to be related to treatment. 
 
3. The participant has symptoms or an intercurrent illness not consistent with the protocol 
requirements or that justifies withdrawal. 
 
4. The participant is lost to follow-up. 
 
5. Other reasons (e.g., pregnancy, development of contraindications to use of IMP). 
 
6. The participant withdraws consent, or the Investigator or Sponsor decides to discontinue the 
participant’s participation in the study. 
 


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A participant may discontinue IMP and be withdrawn from the study for any of the following 
reasons: 
 
1. The participant is noncompliant with the protocol. 
 
2. The participant has laboratory safety results that reveal clinically significant hematological 
or biochemical changes from the baseline values. 
 
3. If the participant is required to start therapy for a concurrent condition that may affect the 
study endpoints, e.g., a disease modifying agent for asthma. 
 
Investigators should contact the Medical Monitor, whenever possible, to discuss the treatment 
discontinuation and withdrawal of a participant in advance of this decision. 
 
Investigators should attempt to obtain information on participants in the case of treatment 
discontinuation and withdrawal.  All results of these evaluations and observations, together with a 
narrative description of the reason(s) for removing the participant, must be recorded in the source 
documents. The CRF must document the primary reason for treatment discontinuation and 
withdrawal. 
     
5.4.1. 
Withdrawal from the Study 
Participants may withdraw from the study at any time at their own request or they may be 
withdrawn at any time at the discretion of the Investigator for safety, behavioral, compliance, or 
administrative reasons. The Investigator will also withdraw a participant if Evelo terminates the 
study. 
 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent.    
 
5.4.2. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if they repeatedly fail to return for scheduled 
visits and is unable to be contacted by the study site. 
 
The following actions must be taken if a participant fails to return to the study site for a required 
study visit: 
 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether the participant wishes to and/or should continue in the 
study. 
 
• Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 2 telephone calls and, if 
necessary, a written message to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the eCRF (date and 
summary of the phone call and copy of the written message in the source documents). 


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If the participant continues to be unreachable, they will be considered to have withdrawn from the 
study. 
 


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6. STUDY TREATMENT(S) 
 
6.1. 
Investigational Medicinal Product(s) 
Investigational Medicinal Product (IMP) is defined as any investigational treatment(s), marketed 
product(s), placebo, or medical device(s) intended to be administered to a study participant 
according to the study protocol.  
 
All participants in this study will be dosed with EDP1815, administered orally for 36 weeks in 
total. EDP1815 will be supplied as capsules that are enteric coated to release the contents upon 
gastric emptying. EDP1815 enteric-coated capsules contain lyophilized Prevotella histicola, 
mannitol, magnesium stearate, colloidal silicon dioxide, hydroxypropyl methylcellulose, 
methacrylic acid-ethyl acrylate copolymer, talc, triethyl citrate, titanium dioxide, and iron oxide.  
 
EDP1815 capsules will be manufactured in the following dose strengths and associated enteric 
coating thickness (EC). The thickness of the capsule enteric coating for Group 3 is thinner (EC2) 
than the capsule enteric coating for Groups 1 & 2 (EC1): 
 
Group 1:  8.0x1010 total cells per capsule (EC1) 
Group 2:  3.2x1011 total cells per capsule (EC1) 
Group 3:  8.0x1010 total cells per capsule (EC2) 
 
The drug substance used for Group 1 and Group 3  and 3 uses the same manufacturing process.  
The drug substance for Group 2 was manufactured using an optimized process to yield a higher 
concentration of microbe per capsule. Drug substance from these two manufacturing processes has 
been demonstrated to be similar in both  DTH mouse and healthy-volunteer human models. All 
IMP, regardless of manufacturing processes, is identical in appearance.  Additional information is 
detailed in the EDP1815 IB. The drug product is manufactured by 
 
   
 
6.2. 
Investigational Medicinal Product(s) to be Administered 
 
The study IMP (EDP1815) will be administered as capsules for 36 weeks in total.   
 
Study IMP is to be taken with water at approximately the same times each day. Participants should 
refrain from consuming acidic drinks (such as cola/soda, coffee, sports and energy drinks, flavored 
waters, and citrus juices) 1 hour either side of dosing and from eating 2 hours before and 1 hour 
after dosing. 
 
No placebo will be administered in this study. 




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6.6. 
IMP Accountability 
An Interactive Response Technology (IRT) system will be used to record IMP dispensing and 
return information on a by-participant basis during the study. Details of any IMP lost, damaged 
(due to breakage or wastage), not used, partially used, disposed of at the study site, or returned to 
the Sponsor or designee must also be recorded. All supplies and pharmacy documentation must be 
made available throughout the study for the Sponsor (or designee) to review. 
 
Participants will utilize an electronic diary (eDiary) to record their IMP intake on a daily basis 
(Section 6.6.1 eDiary). 
 
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of IMP until returned or destroyed. 
 
The Investigator may assign some of the Investigator’s duties for IMP accountability at the study 
site to an appropriate pharmacist/designee. 
 
The Investigator must verify that the IMP is used only in accordance with the protocol. 
 
All used (including empty containers)/partially used, unused, damaged, and/or expired IMP must 
be reconciled and returned to the Sponsor or designee, or it may be destroyed at the site according 
to applicable laws and regulations, and Sponsor SOPs, if applicable.  Investigational medicinal 
product intended for the study cannot be used for any other purpose than that described in this 
protocol. 
 
6.6.1. eDiary 
The primary purpose of the diary is to enhance participant compliance with the protocol.  
Participants will utilize an electronic diary (eDiary) from Day -1 through to the Week 40 Follow-
Up Visit.  It is expected that participants will continue to use the eDiary utilized throughout the 
EDP1815-207 parent study. The eDiary may be either an application (app) that will be downloaded 
to the participant’s mobile smartphone or an eDiary device specifically designated for the purpose 
of collecting information as described below for participants who do not have a mobile smartphone 
or do not wish to download an app to their phone.    
Participants will be asked to capture the following information in their eDiary: 
• Study IMP 
o Confirmation of dosing 
o Date and time of dosing  
o Number of capsules taken, with reasons not taken, if applicable 
• Background Therapy (Emollient(s)) 
o Frequency of usage (number of times a day) 
• Rescue Therapy Usage 
o Confirmation of usage 
•  Daily Peak Pruritus Numerical Rating Scale (PP-NRS) 
o Evaluation of worst itch over previous 24-hour period 
• Daily Sleep Disturbance Numerical Rating Scale (SD-NRS)  
o Evaluation of sleep quality over previous 24-hour period 
 


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Study staff will review the eDiary entries with participants at each visit.  eDiaries will be reviewed 
for completeness and accuracy, and participants will be coached as needed on compliance with the 
protocol.   
 
At the Week 40 Follow-Up or Early Termination Visit (if applicable), the study staff will assist 
the participants to uninstall the eDiary application on their mobile smartphone devices and/or 
collect any eDiary devices that were distributed to the participants. 
 
6.7. 
Drug Compliance 
Participants will use the eDiary to capture compliance with their study IMP.  At specified visits 
per the Schedule of Activities (SOA), the study site staff will check numbers of used/unused 
capsules against diary entries and discuss with the participant the need to self-administer the 
capsules as directed, and to store the IMP according to label instructions. 
 
Prior to the specified study visits per the SOA, study site staff will call participants to remind them 
to bring all empty/partially used IMP wallets and cartons in the original containers to the study site 
for their visit. 
 
If a participant is found to be persistently noncompliant, the Sponsor, in conjunction with the 
Investigator, will decide as to whether the participant should be withdrawn from the study. 
 
6.8. 
Dose Modification 
Dose adjustments, including dose interruptions, and/or decreasing the dose frequency may be 
allowed for safety or tolerability after consultation with the Medical Monitor. The maximum 
permitted interruption at one time is 14 consecutive days and the participants should have 80% 
compliance with IMP administration between any two visits after allowing for permitted 
interruptions. In cases where IMP was interrupted for less than 14 consecutive days, but overall 
compliance is below 80%, the possibility for discontinuation should be discussed with the Medical 
Monitor. 
 
6.9. 
Concomitant Medications and Treatments 
Throughout the study, the participant may be prescribed concomitant medications or treatments 
deemed necessary to provide adequate supportive care at the discretion of the Investigator provided 
that the medications are licensed.  However, it is the responsibility of the Investigator to confirm 
that details regarding the medication are recorded in full in the eCRF. 
 
All concomitant medications and/or treatments received by a participant should be recorded on the 
appropriate source document and eCRF with the following minimum requirements: 
• Drug trade name 
• Total daily dose 
• Dates of administration   
• Reason for use (indication) 
• Dosage information (including dose and frequency)   
 
This will include all prescription drugs, herbal products, vitamins, minerals, over the counter 
(OTC) medications, and vaccines.  Any changes in concomitant medications will also be recorded 


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in the participant’s eCRF.  The participant’s dosing eDiary may contain information relevant to 
the documentation of changes in concomitant medication. 
 
6.9.1. Permitted Concomitant Medications and Treatments 
The following concomitant medications are permitted for use during the study: 
• Concomitant medications for conditions other than AD may continue throughout the study, 
if not meeting any exclusion criteria, and should continue without change in dosage or 
formulation whenever possible. 
• New therapy/treatments, not expected to have any impact on AD, but deemed necessary 
for the welfare of the participant during the study, are permitted. If there is doubt about 
their impact on AD or the ability of the participant to continue in the study, then this should 
be discussed with the Medical Monitor. 
• Topical and oral antibiotics, antiviral, or antifungal therapy. 
• Oral antihistamines. 
• Nasal inhaled and ophthalmic corticosteroids. 
• Non-replicating / non-live vaccines (Section 6.9.3 Immunizations). 
 
All participants must use an emollient at least twice daily throughout the study (Section 6.9.1.1 
Background Therapy). 
 
6.9.1.1. Background Therapy 
All participants must agree to continue with the use of an emollient at least twice daily.  This must 
be a bland emollient which is additive-free, SLS-free, and fragrance-free and may be in cream, gel 
or ointment formulation. Whenever possible, the same brand and formulation of emollient should 
be used throughout the study by the participant. Participants are not allowed to use emollients 
containing additives (e.g., urea, ceramide, nicotinamide). Participants should continue this 
background emollient application twice daily until the Week 40 Follow-up Visit. Missed 
application of emollient will not be considered protocol deviation(s).  On the day of the study 
visits, the participant will be asked to withhold the application of the emollient, and where safe, 
sunscreen and any other topical products until after all study assessments have been performed. 
 
Participants will record their background therapy via the participant eDiary from Day -1 to the 
Week 40 Follow-Up Visit (Section 6.6.1 eDiary). 
 
6.9.1.2. Rescue Therapy 
If required, Investigators may prescribe / recommend prescription of rescue therapy for 
participants experiencing unacceptable worsening of atopic dermatitis. Additionally, individuals 
with uncontrolled atopic dermatitis could be at risk for a secondary skin infection.  These 
participants may be prescribed an antimicrobial therapy to treat the infection as detailed below. 
Rescue therapy use is allowed throughout the entire study. There is no limit on the number of times 
that topical rescue therapy can be prescribed, although Investigators and participants may wish to 
consider whether the study is suitable for them if repeated courses are required. 
 
Rescue therapy, including microbial rescue therapy, should be prescribed as detailed below, and 
any specific deviations should first be discussed with the Medical Monitor. Participants rescued 


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by such topical therapy will continue to take IMP and use of rescue therapy will be documented in 
the participant eDiary (Section 6.6.1 eDiary).  
 
Between Day –1 and Week 16, rescue therapy should be as follows: 
 
For non-sensitive body sites: 
• Moderate potency (grade IV and V – Appendix 14.1) topical corticosteroids, twice daily 
for up to 7 days 
 
For sensitive sites e.g., head and neck: 
• Topical tacrolimus (0.1%), topical pimecrolimus (1%) or grade VII topical corticosteroid, 
twice daily for up to 7 days 
 
After Week 16, participants may be prescribed topical calcineurin inhibitors and/or topical 
corticosteroids of any potency for up to 7 days. It is advised that the lowest effective potency 
topical corticosteroid is chosen.  
 
If topical rescue therapy fails to control symptoms adequately, then the participant should be 
considered for alternative systemic therapy or phototherapy by the Investigator/their practitioner, 
at which point they will be classified as a treatment failure and IMP will be discontinued. 
 
For possible skin infection: 
• Topical: 
o Appropriate courses of topical antimicrobial therapies, such as fucidic acid cream 
(e.g., Fucidin), mupirocin and/or bacitracin, are acceptable for use for skin 
infections, as required 
o If requiring concomitant moderate potency steroid therapy, fucidic acid with 
betamethasone 0.1% (as the valerate ester), (e.g., Fucibet cream) twice daily for up 
to 7 days 
• Oral: 
o Appropriate course(s) of oral antibiotic(s) may be prescribed as per clinical need 
 
6.9.2. 
Prohibited Concomitant Medications and Treatments 
 
6.9.2.1. Prohibited Concomitant Medications  
Use of any of the following concomitant medications during the study require the IMP to be 
immediately discontinued where possible. If a participant requires treatment for atopic dermatitis 
with a prohibited concomitant medication during the study, they will be classified as a treatment 
failure. : 
• Topical Corticosteroids or Topical Calcineurin Inhibitors (unless used as Rescue Therapy, 
Section 6.9.1.2 Rescue Therapy) 
• Topical PDE-4 Inhibitors  
• Topical JAK Inhibitors 
• Bleach baths 
• Phototherapy treatment  
• Tanning beds  


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• Systemic treatments that may lead to clinical improvements in atopic dermatitis, e.g., 
oral, or injectable corticosteroids, methotrexate, azathioprine, cyclosporine, 
mycophenolate mofetil, JAK-inhibitors, biologic therapy, and other systemic 
immunosuppressive therapy (note single dose intra-articular or intra-lesional 
corticosteroid therapy is permitted). 
• Leukotriene Receptor Antagonists 
• Allergen Immunotherapy 
• Live (attenuated) vaccinations: not permitted at any point during the study (Section 6.9.3 
Immunizations). 
 
 
  
6.9.3. 
Immunizations 
Non-replicating / non-live vaccines are permitted during the study.  This includes all SARS-CoV-
2 (COVID) non-live vaccines and non-replicating vaccines. The non-intranasal seasonal flu 
vaccine is permitted, as is the recombinant zoster vaccine (non-live).  However, the first dose of 
IMP should not be taken within a 7-day window of administration of the non-live vaccine or non-
replicating vaccine. 
 
Live (attenuated) vaccinations are not permitted at any point during the study. This includes 
vaccines for measles, mumps, rubella, vaccinia, varicella, zoster (which contains the same virus as 
varicella vaccine but in much higher amount), yellow fever, rotavirus, and influenza (intranasal).   
 
6.10. Blinding 
This is an open-label extension study with all participants taking EDP1815 capsules and as such 
no blinding is required for the study medication in this study. 
 
Investigators and participants will continue to be blinded to the participants treatment assignment 
in the EDP1815-207 parent study in order to minimize bias. 
 
 


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7. STUDY PROCEDURES BY VISIT  
 
No study procedures should be performed prior to the signing of the informed consent form (ICF).  
The ICF will need to be signed prior to any conducting any assessments at the Day -1 visit. 
 
Visit windows are consecutive calendar days and the target visit dates are calculated from the Day 
-1 visit.  
 
The Schedule of Activity (SOA) is presented in Table 4-1.  An overview of each of the study 
assessments is presented in the subsections below.  If a visit is not completed per protocol, it will 
be considered a missed visit.  The site should still contact the participant by telephone to confirm 
that there have not been any adverse reactions.  
 
7.1. 
Day -1 Visit 
The Day -1 visit may occur either the same day as the final treatment visit for the parent study, or 
within 7 days of completing the treatment period of the parent study. If a participant’s Day-1 Visit 
occurs on the same day as the end of treatment visit of the parent study, then any study assessments 
performed at the final treatment visit of the parent study do not need to be repeated (See Table 
4-1).   
 
Each site will sequentially assign a unique identifier to each participant that will be used for the 
duration of the study.   
 
On the day of the visit the participant will be asked to withhold the application of the emollient, 
and where safe, sunscreen and any other topical products until after all study assessments have 
been performed (Section 6.9.1.1  Background Therapy). 
 
The following procedures will be performed on the Day -1 Visit: 
• Obtain written informed consent from participant 
• Assessment of inclusion and exclusion criteria 
• Collection of demographics including year of birth, age, gender, race, and ethnicity 
• Review of changes in medical history and smoking status from the baseline visit of the 
parent study  
• Full physical examination 
• Vital signs (blood pressure, heart rate, respiratory rate, and temperature) including height 
and weight measurements BMI will be calculated using the participant’s height and weight.  
• 12-lead electrocardiogram (ECG) 
• Blood sample collection for safety labs 
• Urine sample collection for pregnancy testing for women of childbearing potential 
(WOCBP), and for urinalysis 
• AD rating scales - vIGA, EASI, BSA, and SCORAD 
• Patient reported clinical rating scales – POEM, DLQI and ADCT 
• PP-NRS and SD-NRS scores in participant diary 
 


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• Digital photographs of the upper and lower body (anterior and posterior) as half body shots. 
Additional photographs of up to six specific body areas, i.e., limbs, trunk and back 
(excluding scalp, genitals, and any identifying features) may also be taken 
• Review and document concomitant medications and therapies 
• Assess and document adverse events (AEs) that occur after participant signs informed 
consent form (ICF) 
 
The participant will be instructed by the investigator or study staff to continue to use their emollient 
as per protocol requirements.  
 
Enrollment Procedures 
• Enroll the participant in IRT after all Day -1 activities are completed and the participant is 
still deemed eligible to participate. 
• If the participant was in Cohort 3 of the EDP1815-207 parent study and is deemed eligible 
for this study, they will be randomized 1:1 to receive either 1.6x1011 total cells of EDP1815, 
or 6.4x1011 total cells of EDP1815 in this study. An IRT will be used for assigning eligible 
participants from this cohort into to a dosing group in EDP1815-208. Sufficient IMP will 
be dispensed to cover the first 4 weeks of the treatment period. The participant will be 
instructed to take their first dose of IMP at home on Day 1 of the study.   
• Assist the participant in the transitioning of apps into the EDP1815-208-study eDiary on 
their smartphone device and provide instructions on completion of eDiary 
 
7.2. 
Treatment Period (Week 4 – Week 36) 
These visits will take place approximately every month from Week 4 until Week 16, and 
approximately every 2-4 months from Week 16 until Week 36. Participants may dose at home on 
the day of the treatment period visits. Prior to these visits, the participant will be asked to withhold 
the application of the emollient, and where safe, sunscreen, and any other topical products until 
after all study assessments have been performed.  See Section 6.9.1.1 Background Therapy. 
 
The following procedures will be performed at each visit during this period: 
• Brief physical examination (excluding Week 36 which will consist of a full physical 
examination) 
• Vital signs including weight measurement 
• 12-lead ECG 
• Urine sample collection for pregnancy testing (women of childbearing potential only) 
• Blood sample collection for safety labs  
• Blood sample collection for biomarkers (Week 36/Early Termination only) 
• Urine for urinalysis 
• Digital photographs of the same lesions/ body area taken at the Day -1 Visit 
• AD rating scales - vIGA, EASI (and BSA), and SCORAD 
• Patient reported clinical rating scales – POEM, DLQI and ADCT 
• Collection and or review PP-NRS and SD-NRS scores in participant diary 
• Review and documentation of concomitant medications and therapies including emollient 
use 
• Assessment and documentation of adverse events (AEs)  


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• Review of participant compliance with IMP administration and use of eDiary  
• Collection and reconciliation of returned IMP, i.e., IMP accountability. Participants will 
be required to return all empty cartons and any remaining IMP at the Week 36 visit  
• Dispensation of IMP (Excluding Week 36 i.e., the End of Treatment visit) 
 
7.3. 
Week 40 Follow Up/ End of Study Visit  
This visit will be the last visit in the study and will take place approximately 4 weeks after the last 
dose of IMP. Prior to this visit, the participant will be asked to withhold the application of the 
emollient, and where safe, sunscreen, and any other topical products until after all study 
assessments have been performed.  See Section 6.9.1.1 Background Therapy. 
 
The following procedures will be performed: 
• Brief physical examination 
• Vital signs including weight measurements  
• 12-lead ECG 
• Urine sample collection for pregnancy testing (women of childbearing potential only) 
• Blood sample collection for safety labs  
• Urine sample collection for urinalysis 
• Digital photographs of the same lesions/body area taken at the Day -1 Visit 
• AD rating scales - vIGA, EASI (and BSA), and SCORAD 
• Patient reported clinical rating scales – POEM, DLQI and ADCT 
• Collection and or review of PP-NRS and SD-NRS scores in participant diary 
• Review of and documentation of concomitant medications and therapies including 
emollient use 
• Assessment and documentation of adverse events (AEs)  
• Removal of eDiary application from smartphone/ collection of eDiary device  
 
7.4. 
Early Termination Visit 
Participants who withdraw prematurely from the study should have an early termination visit using 
the Early Termination Visit schedule within 14 days of asking to withdraw consent or within 72 
hours of starting any AD therapy if their withdrawal was due to treatment failure. The Early 
Termination Visit will consist of the same assessments and procedures as  the End of Treatment 
Study Visit at Week 36. Once all assessments are complete, study staff will assist the participant 
to uninstall the mobile application from their smartphone device. The participant will also be asked 
to have a final telephone call 28 days (+3 days) after taking their last dose of IMP for safety 
assessments. The date of this telephone call will be considered the end of study date for these 
participants.  
 
7.5. 
Unscheduled Visits 
Unscheduled visits are visits that fall outside of the scheduled visits indicated in the SOA.  These 
visits and the findings are to be recorded on the appropriate eCRFs.   
 


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7.6. 
COVID-19 Pandemic 
Parts or all of this study are expected to run during the COVID-19 pandemic.  As a result, a 
thorough risk analysis has been carried out.  In addition, a number of mitigation steps have been 
considered, for example, the scenarios of individual self-isolation or local/national lockdown. 
 
7.6.1. 
EDP1815 and Risk of COVID-19 Infection 
EDP1815 does not broadly impair either innate or adaptive immune responses, as detailed in a full 
risk-assessment in Appendix 14.3.  Anti-viral responses such as cytotoxic T-cell production of 
interferon-gamma, innate anti-viral production of interferon-alpha and interferon-beta, and the 
generation of high-affinity antibodies are all preserved pre-clinically after treatment with 
EDP1815. There is no pre-clinical or clinical evidence of EDP1815 causing immunosuppression. 
 
EDP1815 was investigated as a treatment of patients hospitalized with COVID-19 infection but 
no safety or efficacy data have yet been reported from these  studies.  
 
7.6.2. 
EDP1815 and COVID-19 Vaccination 
As detailed in Section 6.9.3 Immunizations of this protocol, live and live-attenuated vaccines 
should not be given with EDP1815. Non-live and non-replicating vaccines are permitted, and it is 
not expected that the safety of participants will be impacted by their co-administration. The 
efficacy of the vaccines co-administered with EDP1815 has not been tested. 
 
7.6.3. 
EDP1815-208 and COVID-19 Infection 
Self-isolation or a positive COVID-19 test in a well participant may not be a reason in itself to stop 
dosing since EDP1815 is not expected to increase the risks associated with COVID-19. If a study 
participant is diagnosed with COVID-19 infection (diagnosed clinically or by laboratory tests), the 
participant may continue study treatment if the Investigator considers that there is a positive 
individual risk/benefit balance. This should be discussed with the Medical Monitor. 
 
7.6.4. 
COVID-19 Mitigation Steps  
If a participant with COVID-19 must self-isolate or quarantine while on study, and a study visit 
coincides with this self-isolation or quarantine, the study visit will be missed and the reason the 
visit was not done recorded in the source documents with COVID-19 isolation / lockdown as the 
reason for the visit not completed.   
 
In lieu of the study visits, the participant should receive a telephone call to assess adverse reactions, 
ascertain study IMP status (i.e., did the participant self-interrupt taking IMP) and emollient usage, 
and collect information on any concomitant medications, including any rescue therapy.  
Information should be recorded in the participant’s source documents and entered into the EDC, 
as applicable.  
 
The participant must try and attend all study visits; however, the Week 16 and Week 36 study visit 
should not be missed wherever possible. These visits, therefore, may be conducted outside of the 
protocol study window.  Please contact the Medical Monitor to discuss further.   
 


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7.7. 
Missed Visits and Procedures 
Missed visits and any procedures not performed (not attempted) for reasons other than screen 
failure, illness, injury, or progressive disability (i.e., the participant is physically unable to perform 
test) will be reported as protocol deviations.  
 
Procedures or visits not performed due to screen failure, illness, injury, or disability, including 
procedures that were attempted but failed (i.e., blood samples unable to be drawn after multiple 
attempts) will not be reported as protocol deviations.  
 
 
 


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8. EFFICACY ASSESSMENTS 
 
Assessments will be performed at designated time-points throughout the study for efficacy 
evaluations. In addition to the assessments below, participants will provide any updates to the 
existing information on their demographics and smoking history, past medical history (including 
diagnosis of atopic dermatitis), as well as concomitant medication usage.  
 
All efficacy assessments will be completed at the study site utilizing a site tablet at the specified 
visits as indicated on the SOA.  The participants will be trained on how to complete the assessments 
that are considered patient reported outcomes (PRO). PROs should be completed prior to 
conducting any assessments with the exception of signing the consent form on Day-1. The same 
reviewer should conduct the skin assessments for a single participant at each visit wherever 
possible, and at a minimum for the Day -1, Week 16, and Week 36 assessments.   
 
The Investigators and site staff will be provided with further details on how to perform the 
following assessments and how to calculate each of the scores (if applicable).   
 
8.1. 
Eczema Area and Severity Index 
The Eczema Area and Severity Index (EASI) is a validated measure of eczema severity, which 
considers a combination of the body surface area affected across 4 body regions, and the severity 
of the clinical signs of erythema, oedema/induration, excoriation and lichenification (Eczema, 
n.d.). The EASI score ranges from 0 – 72 (EASI, 2017 Jan). EASI-50, EASI-75, EASI-90 
responses are defined as at least 50%, 75% and 90% decrease from baseline EASI score 
respectively. 
 
8.2. 
Validated Investigator’s Global Assessment 
The Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) will be 
used to describe the overall appearance of lesions at a given time-point (Simpson E, 2020 Sep). 
There is a standardized grading system based on an overall assessment of the degree of erythema, 
papulation/induration, lichenification, and oozing/crusting. In indeterminate cases, extent will be 
used to differentiate between scores – but otherwise extent is not used in the scoring system. The 
vIGA score ranges from 0 (Clear skin) to 4 (Severe disease). 
 
8.3. 
SCORing Atopic Dermatitis 
The SCORing Atopic Dermatitis (SCORAD) is a clinical tool which is also used to assess the 
extent and severity of eczema, to assess treatment effects. There is an investigator-rated area score 
which uses the rule of nines to assess disease extent, and a disease intensity score comprising 
erythema, swelling, oozing/crusting, excoriation, lichenification, and dryness. Additionally, there 
is a subjective symptoms component which considers itch and sleeplessness scored using a visual 
analogue scale. These scores combine to give a SCORAD score between 0 – 103 (Dermatitis, 
1993). 
 
8.4. 
Patient Oriented Eczema Measure 
The Patient Oriented Eczema Measure (POEM) is a simple PRO assessment tool for monitoring 
disease severity.  It includes a series of 7 questions, measuring itch, sleep, bleeding, 
weeping/oozing, cracking, flaking, and dryness/roughness over the last week, and is scored by 


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the participant.  Each of the 7 questions is scored from 0 (no days) to 4 (every day), giving a 
POEM score range from 0 to 28, with higher scores representing higher disease severity 
Charman, 2004 and Charman, 2013). The minimally clinically important difference threshold is 
a change of ≥3.4 points on average (Schram, et al., 2011). For the purposes of changes within an 
individual participant, a response will therefore be considered to be a ≥4-point change from 
baseline. 
 
8.5. 
Dermatology Life Quality Index 
The Dermatology Life Quality Index (DLQI) is a validated PRO instrument comprised of 10 
questions to assess how a participant’s skin disease has affected their quality of life over the 
previous week (Finlay AY, 1994). The DLQI score ranges from 0 to 30, with higher scores 
indicating greater impairment of quality of life. A DLQI score of 0 or 1 is considered as having no 
effect on a participant’s quality of life, and a 4-point change from baseline is considered the 
minimal clinically important difference threshold (Basra, 2015). 
 
8.6. 
Peak Pruritus Numerical Rating Scale (PP-NRS)  
The Peak Pruritus Numerical Rating Scale (PP-NRS) is a scale from 0 (“no itch”) to 10 (“worse 
imaginable itch”) for participants to rate the worst itch they have experienced over the previous 24 
hours (Phan, 2011).  The PP-NRS will be completed daily via a daily questionnaire from the Day-
1 Visit to the Week 40 visit. A ≥2-4-point change from baseline is considered the minimally 
clinically important difference threshold (Yosipovitch, et al., 2019). 
 
8.7. 
Sleep Disturbance Numerical Rating Scale (SD-NRS)  
The Sleep Disturbance Numerical Rating Scale (SD-NRS) is a scale from 0 (“best possible sleep”) 
to 10 (“worse possible sleep”) for participants to rate the worst sleep they have experienced over 
the previous 24 hours. The SD-NRS will be completed via a daily questionnaire from the Day-1 
Visit to the Week 40 visit. A ≥2 point change from baseline is considered the minimally clinically 
important difference threshold (Dias-Barbosa, Matos, & Vernon, 2020). 
 
8.8. 
Body Surface Area 
The Body Surface Area (BSA) is a measure of the extent of atopic dermatitis at a given time. It is 
calculated by estimating the amount of active atopic dermatitis using the number of participant’s 
handprints, where one handprint (including digits) represents 1% body surface area. The BSA 
provides another assessment of disease severity by looking at coverage of body surface and is 
sometimes assessed as a product of the IGA*BSA as a further marker of disease severity and 
response to treatment (Suh, 2020). 
 
8.9. 
Atopic Dermatitis Control Tool 
The Atopic Dermatitis Control Tool (ADCT) is a 6-question PRO instrument used to detect change 
of disease activity in a person over time.  There are six main areas that assess the multi-dimensional 
aspects of disease control over the course of a week, scored between 0-4, with a minimum score 
of 0 and a maximum score of 24.  A higher score indicates lower AD control.  A change of 5 points 
is the threshold for meaningful within person change, where a decrease of 5 or more points 
indicates clinically relevant improvement of AD control and an increase of 5 or more points 
indicates a clinically relevant worsening of AD control (Pariser, 2020). 
 


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9. SAFETY ASSESSMENTS 
 
The adverse event (AE) definitions and reporting procedures provided in this protocol comply with 
all applicable regulations and International Conference on Harmonization (ICH) guidelines. The 
Investigator will carefully monitor each participant throughout the study for possible adverse 
events.  
 
9.1. 
Adverse Events 
An adverse event (AE) is any unfavorable and unintended sign (including a clinically significant 
abnormal laboratory finding, for example), symptom, or disease temporally associated with a 
study, use of a drug product or device whether or not considered related to the drug product or 
device.  
 
Signs or symptoms of the condition/disease for which the IMP is being studied should be recorded 
as AEs only if their nature changes considerably or their frequency or intensity increases in a 
clinically significant manner as compared to the clinical profile known to the investigator from the 
participant’s history or from Day -1. 
 
9.1.1. 
Adverse Events of Special Interest 
There are no prespecified AEs of special interest (AESI) for this study. 
 
9.2. 
Adverse Drug Reactions 
Adverse drug reactions (ADR) are all noxious and unintended responses to a medicinal product 
related to any dose. The phrase “responses to a medicinal product” means that a causal relationship 
between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the 
relationship cannot be ruled out. Therefore, a subset of AEs can be classified as suspected ADRs, 
if there is a causal relationship to the medicinal product. A suspected unexpected serious adverse 
reaction (SUSAR) is another subset of ADR, which includes all adverse reactions that are 
suspected to be related to an investigational medicine product and are both serious and unexpected. 
 
9.3. 
Serious Adverse Events 
A serious adverse event (SAE) is defined as an adverse event that meets any of the following 
criteria:  
 
• Results in death. 
 
• Is life-threatening that is, poses an immediate risk of death as the event occurred. 
− This serious criterion applies even if the participant, in the view of the Investigator or 
Sponsor, is at immediate risk of death from the AE as it occurs.  It does not apply if an AE 
hypothetically might have caused death if it were more severe. 
 
• Requires inpatient hospitalization or prolongation of existing hospitalization.  
− A participant admitted to a hospital, even if he/she is released on the same day, meets the 
criteria for the initial inpatient hospitalization. An emergency room visit that results in 
admission to the hospital would also qualify for the initial inpatient hospitalization criteria. 
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qualify for this criterion and, instead, should be evaluated for one of the other criteria in 
the definition of serious (e.g., life-threatening adverse experience, important medical 
event). 
− Hospitalizations for reasons not associated with the occurrence of an AE (e.g., preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner) do not qualify for reporting.  
◦ 
For example, if a participant has a condition recorded on his/her medical history and 
later has a preplanned surgery for this condition, it is not appropriate to record the 
surgery or hospitalization as an SAE, since there is no AE upon which to assess the 
serious criteria.  
◦ 
Please note that, if the pre-existing condition has worsened or manifested in an unusual 
or uncharacteristic manner, this would then qualify as an AE and, if necessary, the 
seriousness of the event would need to be determined. 
 
• Results in persistent or significant disability or incapacity. 
− This serious criterion applies if the “disability” caused by the reported AE results in a 
substantial disruption of the participant’s ability to carry out normal life functions. 
 
• Results in a congenital anomaly or birth defect in the offspring of the participant (whether the 
participant is male or female). 
 
• Is an important medical event that, based upon appropriate medical judgment, may jeopardize 
the participant, and may require medical or surgical intervention to prevent one of the other 
outcomes listed in the definition of serious. 
− Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. 
 
9.4. 
Reporting and Recording AEs 
The Investigator will carefully monitor each participant throughout the study for possible AEs.  In 
order to confirm complete safety data collection, all AEs occurring during the study (i.e., after the 
signing of the Informed Consent form) must be reported in the CRF. AEs reported during the 
parent study that are ongoing at the end of treatment visit will continue to be followed up during 
EDP1815-208 until resolution or the participants completes the study, whichever is first. 
 
All AEs will be collected and reported in the electronic data capture (EDC) system and compiled 
into reports for periodic reviewing by the Medical Monitor. The Medical Monitor shall promptly 
review all information relevant to the safety of the investigational product, including all serious 
adverse events (SAEs). Special attention will be paid to those that result in permanent 
discontinuation of the investigational product being studied, whether serious or non-serious. 
  
If the investigator learns of any SAE, including a death, at any time after a participant has been 
discharged from the study, and he/she considers the event to be reasonably related to the IMP or 
study participation, the investigator must immediately notify the sponsor (or designee). 
 


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Serious AEs that occur more than 30 days after the last dose of IMP need not be reported unless 
the investigator considers them related to the IMP. 
 
9.4.1. 
Assessment of AEs 
At every study visit, participants will be asked a standard non-leading question to elicit any 
medically related changes in their well-being. They will also be asked if they have used any new 
medications, changed concomitant medication regimens (prescription or OTC medications), or had 
unplanned visits to their general practitioner since the last visit. 
 
In addition to participant observations, AEs identified from any study data (e.g., laboratory values, 
physical examination findings, ECG changes) or identified from review of other documents (e.g., 
participant diaries) that are relevant to participant safety and considered clinically significant will 
be documented on the AE page in the CRF. 
 
If the participant reports an adverse event, the following will be recorded in the source and on the 
eCRF:  
1. Description of the event  
2. Date and time of onset and resolution (duration)  
3. CTCAE v5.0 grade (Grade 1 – 5)  
4. Seriousness (does the event meet the above definition for an SAE) 
5. Causality, relation to investigational product  
6. Action taken regarding investigational product  
7. Outcome 
8. If any Concomitant Medications were given due to the AE 
9. Whether the AE resulted in participant withdrawal from the study 
10. Investigator-specified assessment if the AE is related to a recent/current COVID 
infection 
11. If a COVID positive PCR test received within the last 14 days 
 
Signs or symptoms of a participant’s atopic dermatitis should be recorded as AEs only if their 
nature changes considerably or their frequency or intensity increases in a clinically significant 
manner as compared to the clinical profile known to the Investigator from the participant’s history.   
 
9.4.2. 
Assessment of Severity 
The severity, or intensity, of an AE refers to the extent to which an AE affects the participant’s 
daily activities or their health. The intensity of the AE will be rated in accordance with the CTCAE 
Version 5.0.  Adverse events related to temperature and abnormal laboratory results that are not 
found in the CTCAE Version 5.0 will be rated in accordance with the FDA Guidance for Industry 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials [Appendix 14.4 Toxicity Grading Scale]. 
 
Changes in the severity of an AE should be documented to allow an assessment of the duration of 
the event at each level of intensity to be performed. Adverse events characterized as intermittent 
do not require documentation of onset and duration of each episode. 
 


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9.4.3. 
Assessment of Causality 
The investigator’s assessment of an AE’s relationship to IMP is part of the documentation process. 
Regardless of the investigator's assessment of an AE's relationship to IMP, the AE must be 
reported.  
 
The relationship or association of the IMP in causing or contributing to the AE will be 
characterized using the following classification and criteria: 
 
Unrelated:   There is no association between the IMP and the reported events. 
 
Possible: 
Treatment with the IMP may have caused or contributed to the AE, i.e., the 
event follows a reasonable temporal sequence from the time of drug 
administration or follows a known response pattern to the IMP but could also 
have been produced by another factor. 
 
Probable: 
A reasonable temporal sequence of the event with drug administration exists 
and based upon the known pharmacological action of the drug, known or 
previously reported adverse reactions to the drug or class of drugs, or judgment 
based on the investigator’s clinical experience, the association of the event with 
the IMP seems likely. The event disappears or decreases on cessation or 
reduction of the dose of IMP. 
 
Definite: 
A definite causal relationship exists between drug administration and the AE, 
and other conditions (concurrent illness, progression/expression of disease 
state, or concurrent medication reaction) do not appear to explain the event. The 
event reappears or worsens if the IMP is re-administered. 
 
9.4.4. 
Description of Adverse Events 
When recording an AE, the Investigator should use the overall diagnosis or syndrome using 
standard medical terminology, rather than recording individual symptoms or signs. The eCRF and 
source documents should be consistent. Any discrepancies between the participant’s own words 
on his/her own records (e.g., diary card) and the corresponding medical terminology should be 
clarified in the source documentation. 
 
Details for completion of the Adverse Event eCRF are described in the eCRF Completion 
Guidelines. 
 
9.5. 
Reporting Serious Adverse Events 
Serious Adverse Events (SAEs) must be reported to the Medical Monitor and Sponsor 
immediately, without undue delay but no later than within 24 hours of the site learning of the SAE. 
 
To report the SAE, the investigator must record the SAE on the AE eCRF in the EDC system as 
well as any relevant CRF forms (e.g., drug dispensation CRF, applicable laboratory CRF). When 
the AE CRF is completed, 
Safety personnel will be automatically notified electronically 
and will retrieve the form. 
 




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the Paper SAE Form provided to 
 Clinical Safety (Section 9.5 Reporting Serious 
Adverse Events).  
 
In the event of a symptomatic overdose, the Investigator should: 
 
1. Manage the participant symptomatically with supportive care 
2. Contact the Medical Monitor urgently 
3. Document the quantity of the excess dose in the eCRF 
4. Document the overdose symptoms and their duration in the eCRF 
 
Doses of EDP1815 capsules that have previously been administered in participants with atopic 
dermatitis include a dose of 8.0 x 1011 cells taken once daily for 16 weeks, and 1.28 x 1012 cells 
taken once daily for 8 weeks. There are no specific adverse events expected in an overdose; 
however, the participant should be closely and carefully monitored. There is no specific treatment 
or antidote, but supportive clinical care should be provided as dictated by the participant’s clinical 
status. 
 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 
 
9.8. 
Safety Signal Detection 
Selected data from this study will be reviewed periodically to detect as early as possible any safety 
concern(s) related to the IMP so that Investigators, participants, regulatory authorities, and 
IRBs/IECs will be informed appropriately and as early as possible. 
 
The Medical Monitor or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs.  
DM will perform ongoing SAE reconciliations in collaboration with the PV 
representative. 
 
As appropriate for the stage of development and accumulated experience with the IMP, medically 
qualified personnel at the Sponsor may identify additional safety measures (e.g., AEs, vital signs, 
laboratory, or ECG results) for which data will be periodically reviewed during the course of the 
study. 
 
9.9. 
Study Halting Criteria  
The study will be halted if any of the following occur: 
 
• One or more SAE considered definitely or probably related to the investigational product. 
 
• Three or more participants with grade 3 AEs of the same type considered definitely, 
probably, or possibly related to the investigational product.  
 
• Any participant develops a documented Prevotella histicola infection in a sterile space 
confirmed by clinical culture and/or qPCR. 
 
 


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9.10. Laboratory Measurements 
Standard laboratory analyses to understand safety and tolerability include the following 
measurements: 
 
Hematology 
Biochemistry 
Urinalysis 
Complete Blood Count with 
differentials: 
Alanine Aminotransferase (ALT) 
Bilirubin 
Hemoglobin 
Aspartate Aminotransferase (AST) 
Blood 
Hematocrit 
Creatinine 
Glucose 
Platelet count 
C-Reactive Protein (CRP) 
Ketones 
Red blood count (with percent 
reticulocytes) 
Gamma-glutamyl transpeptidase 
(GGT) 
Nitrites 
Mean Corpuscular Hemoglobin 
(MCH) 
Potassium 
pH 
Mean Corpuscular Hemoglobin 
Concentration (MCHC) 
Sodium 
Protein 
Mean Corpuscular Volume 
(MCV) 
Total Bilirubin 
Specific 
Gravity 
White blood cell count: 
Urea 
 
Basophils 
 
 
Eosinophils  
 
 
Lymphocytes 
 
 
Monocytes  
 
 
Neutrophils 
 
 
 
For WOCBP, urine pregnancy testing will be conducted at each study visit.   
 
Additional testing may be ordered if needed, to further assess an adverse event (AE), or if there is 
any suspicion that a participant may be pregnant, throughout the course of the study. 
 
Only abnormal laboratory test results (hematology, clinical biochemistry, or urinalysis) or other 
safety assessments (e.g., ECGs, vital sign measurements), which are clinically significant in the 
medical and scientific judgment of the investigator, are to be recorded as AEs or SAEs. 
 
A central laboratory will be used for all laboratory analyses. Details of sample collection and 
handling procedures will be provided in the specific laboratory manual.  
 
9.10.1. Review of Laboratory Measurements 
The Investigator must complete a timely review of the laboratory reports, document this review, 
and record any clinically relevant changes occurring during the study. If the laboratory reports are 
not transferred electronically, the values must be filed with the source information (including 
reference ranges). In most cases, clinically significant abnormal laboratory findings are those that 
are not associated with the underlying disease, unless judged by the Investigator to be more severe 
than expected for the participant's condition. 
 


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All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 30  days after the last dose of IMP should be repeated until the values return 
to normal or baseline value or are no longer considered clinically significant by the Investigator or 
Medical Monitor. If such values do not return to normal/baseline within a time judged reasonable 
by the Investigator, the etiology should be identified, and the Sponsor notified. 
 
All protocol-required laboratory assessments, as defined in this section, must be conducted in 
accordance with the laboratory manual and the SOA. If laboratory values from non-protocol 
specified laboratory assessments performed at the institution’s local laboratory require a change in 
participant management or are considered clinically significant by the Investigator (e.g., SAE or 
AE or dose modification), then the results must be recorded on the Adverse Events eCRF.  
 
9.10.2. Blood Volumes 
The planned maximum amount of blood collected from each participant over the duration of the 
study, including any extra assessments that may be required, will not exceed 100 mL. Repeat or 
unscheduled samples may be taken for safety reasons or for technical issues with the samples. The 
planned maximum amount of blood collected from each participant at a single visit will not exceed 
20 mL, and the planned maximum amount of blood collected from each participant over 30 days 
will not exceed 20 mL. 
 
9.11. Biomarkers  
 
9.11.1. Immune Protein Biomarkers  
Immunoglobulin E (IgE) are antibodies produced by the immune system and are often raised in 
patients with AD, particularly with the phenotype known as ‘extrinsic’ AD (Renert-Yuval, 2021). 
IgE is a recognized biomarker of disease severity in AD and is regularly measured in clinical 
practice. It is being measured in participants to see if treatment response can be predicted by Day 
1 IgE level, and also whether IgE levels improve on treatment as a biomarker of treatment success.  
In addition to the IgE levels, other immune protein markers such as cytokines may be measured 
from this sample in order to assess the anti-flammatory and disease-modifying effects of EDP1815. 
These samples will be collected at the end of study visit of the parent study and at Week 36/Early 
Termination Visit of this study. 
 
9.11.2. Transcription Analysis 
RNA will be collected from whole blood samples at the end of study visit of the EDP1815-207 
parent study and at Week 36/Early Termination Visit of this study to quantify inflammation 
markers in immune cells to assess the effect of EDP1815.  These samples may be analyzed subject 
to the clinical data in the trial.  The genes to be analyzed may include those related to host immune 
response as well as those related to the disease pathology. 
 
9.12. Other Safety Measurements 
 
9.12.3. Vital Signs, Height and Weight 
Vital signs will be obtained after the participant has been in a seated position for approximately 5 
minutes. Vital signs, including systolic and diastolic blood pressure, pulse rate (radial 
artery)/minute, respiratory rate/minute, and temperature.  Height will be measured and recorded at 
the Baseline Visit of the parent study only. Weight will be assessed at specified visits (without 


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shoes and outdoor wear e.g., coats).  Body mass index will be calculated from the height and 
weight.  Investigators should pay special attention to clinical signs related to previous serious 
illness.  
  
9.12.4. Physical Examination 
A physical examination (PE) will be performed and recorded in source at specified visits.  Only 
abnormal, clinically significant findings will be recorded as AEs on the eCRF. 
 
The following systems will be examined when a full PE is indicated: general appearance, 
cardiovascular, lungs, abdomen, musculoskeletal, central nervous system, lymph nodes and skin.  
 
The following systems will be examined when a brief PE is indicated: general appearance, 
cardiovascular, lungs, abdomen, and skin. 
 
9.12.5. 12-Lead Electrocardiogram 
A single 12-lead electrocardiogram (ECG) will be obtained at specified visits using an ECG 
machine that automatically calculates heart rate and measures PR, RR, QRS, QT and QTcF 
(Fridericia) intervals.   
 
A single ECG tracing is to be obtained on the day of the visit after the participant has been in a 
lying position for approximately 5 minutes.  If in the opinion of the Investigator, there appear to 
be clinically significant findings, it should be repeated.  If the repeated tracing also appears 
clinically significant, the Investigator should report the abnormality as an AE and consult with the 
Medical Monitor to decide whether the participant should continue treatment in the study. 
 
9.13. Non-Safety Measurements 
 
9.13.1. Digital Photography 
Digital photographs should be taken of the upper and lower body (upper & lower anterior and 
upper & lower posterior) as half body shots.  Additional photographs of up to six specific body 
areas, i.e., limbs, trunks, and back, will also be taken.  The same locations photographed in the 
parent study should be followed through this study for each participant.    
 
Procedural details for digital photography will be provided to the sites. 
 
 




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pharmacy records, care records, ECG, or other printouts, completed scales, quality of life 
questionnaires, certified copies, or video, for example. Source documents should be kept in a 
secure, limited access area. 
 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They must not be obscured by correction fluid or have temporary attachments (such 
as removable self-stick notes). Photocopies and/or printouts of CRFs are not considered acceptable 
source documents. 
 
The following data will be considered as electronic source and therefore, will not be recorded 
directly into the EDC and will not appear in a separate source document as defined above. 
However, Paper source documents may be utilized for collection of PROs and COAs listed below 
should there be an unforeseeable circumstance (such as a power outage) and the electronic source 
is unavailable.  Any information about a participant that is collected during this study will remain 
secured and confidential and will be handled per applicable regulations (i.e., data collected via 
mobile applications). 
 
• Participant Electronic Diary (eDiary) including IMP, emollient, and rescue therapy 
usage and PP-NRS and SD-NRS daily questionnaire.  
• Patient Reported Outcome Measurements (PROs), including POEM, DLQI and ADCT.  
•  Clinician Outcome Assessments (COAs) including EASI, BSA, IGA, and SCORAD. 
 
Source documents that are computer generated and stored electronically must be printed for review 
by the monitor (e.g., ECG reports, laboratory reports). Once printed, these copies should be signed 
and dated by the Investigator and become a permanent part of the participant’s source documents. 
The Investigator will facilitate the process for enabling the monitor to compare the content of the 
printout and the data stored in the computer to ensure all data are consistent. 
 
10.2.2. Source Data Verification 
Source data verification demonstrates accuracy and credibility of the data obtained. During 
monitoring visits, reported data are reviewed with regard to being accurate, complete, and 
verifiable from source documents (e.g., participant files, recordings from automated instruments, 
tracings [ECG], x-ray films, laboratory notes). All data reported on the eCRF should be supported 
by source documents, unless otherwise specified in Section 10.2.1 Definition of Source 
Documents. 
 
10.3. Data Management 
 
10.3.1. Data Quality Assurance 
This study will be conducted according to ICH E6(R2) risk and quality processes described in the 
applicable procedural documents.  The quality management approach to be implemented in this 
study will be documented and will comply with the current ICH guidance on quality and risk 
management.  The Sponsor assumes accountability for actions delegated to 
. 
 


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10.3.2. Case Report Form Completion 
The Investigator is responsible for prompt reporting of accurate, complete, and legible data in the 
electronic CRFs and in all required reports.  Any change or correction to the CRF after saving must 
be accompanied by a reason for the change. Corrections made after the Investigator’s review and 
approval (by means of a password/electronic signature) will be reapproved by the Investigator. 
The Investigator should maintain a list of personnel authorized to enter data into the electronic 
CRF. 
 
Detailed instructions will be provided in the CRF Completion Guidelines. 
 
10.3.3. Data Entry and Reconciliation 
Case Report forms/external electronic data will be entered/loaded into a validated electronic 
database that is validated and compliant with US Title 21 CFR Part 11.  Each person involved with 
the study will have an individual username and password that allows for record traceability. 
 
Computerized data cleaning checks will be used in addition to manual review to check for 
discrepancies and to confirm consistency of the data. A quality review of the data will be performed 
by the site with additional reviews by the clinical monitor through source data verification.  
 
An electronic audit trail system will be maintained within the Clinical Data Management System  
(CDMS) to track all data changes in the database once the data have been saved initially into the 
system or electronically loaded. Regular backups of the electronic data will be performed. 
 
Paper copies of the eCRFs and other database reports may be printed by the investigator. 
This system provides site staff, monitors, and reviewers with access to hard copy audits, 
discrepancy reviews, and investigator comment information.  
 
After all data reviews and query resolutions are complete, the Statistical Analysis Plan (SAP) is 
approved and signed, and any summary/analysis populations are approved, the database will be 
locked. 
 
10.3.4. Participant Enrollment Log/Participant Identification Code List 
The participant’s enrollment will be recorded in the Participant Enrollment Log. 
 
The Investigator will keep a Participant Identification Code list. This list remains with the 
Investigator and is used for unambiguous identification of each participant. 
 
The participant’s consent and enrollment in the study must be recorded in the participant’s medical 
record. These data should identify the study and document the dates of the participant’s 
participation. 
 
10.4. Termination of the Study 
The Sponsor reserves the right to temporarily suspend or prematurely discontinue this study either 
at a single site, multiple sites, or at all sites at any time for any reason including, but not limited 
to, safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or 
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If the study is prematurely terminated or suspended, the Sponsor (or its representative) will inform 
the Investigators/institutions and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension, in accordance with applicable regulatory 
requirement(s). The IRB/IEC should also be informed and provided with reason(s) for the 
termination or suspension by the Sponsor or by the Investigator/institution, as specified by the 
applicable regulatory requirement(s). In addition, arrangements will be made for the return of all 
unused IMP/investigational device and other material in accordance with the Sponsor’s procedures 
for the study. 
 
10.5. Archiving and Data Retention 
The Investigator will maintain adequate records for the study, including CRFs, medical records, 
laboratory results, Informed Consent documents, drug dispensing and disposition records, safety 
reports, information regarding participants who discontinued, and other pertinent data. 
 
All essential documents are to be retained by the Investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP/investigational device. These 
documents should be retained for a longer period, however, if required by the applicable regulatory 
requirement(s) or by an agreement with the Sponsor. (EMEA, 2002 Jul). 
 
The Investigator will contact the Sponsor for authorization prior to the destruction of any study 
records or in the event of accidental loss or destruction of any study records. The Investigator will 
also notify the Sponsor in writing should he/she relocate or move the study -related files to a 
location other than that specified in the Sponsor’s Trial Master File (TMF). 
 
10.6. Audit and Inspection 
The Investigator will permit study-related audits mandated by the Sponsor, after reasonable notice, 
and inspections by domestic or foreign regulatory authorities. 
 
The main purposes of an audit or inspection are to confirm that the rights and well-being of the 
participants enrolled have been protected, that enrolled participants (i.e., signing consent and 
undergoing study procedures) are appropriate for the study, and that all data relevant for the 
evaluation of the IMP/investigational device have been processed and reported in compliance with 
the planned arrangements, the protocol, investigational site, and IRB/IEC SOPs, ICH GCP, and 
applicable regulatory requirements. 
 
The Investigator will provide direct access to all study documents, source records, and source data. 
If an inspection by a regulatory authority is announced, the investigator will immediately inform 
the Sponsor (or designee). 
 
10.7. Good Clinical Practice 
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the Investigator, 
institution, institution staff, or designees of the Sponsor will lead to prompt action by the Sponsor 
to secure compliance. Continued noncompliance may result in the termination of the site’s 
involvement in the study. 
 


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11. STATISTICS 
 
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan.   
 
11.1. General Statistical Considerations 
Statistical analysis will be performed using SAS software Version 9.3 or later.  
 
Continuous variables will be summarized using the mean, standard deviation, median, minimum 
value, and maximum value. Categorical variables will be summarized using frequency counts and 
percentages.  
 
No inferential statistical testing will be performed.  Data will be displayed using summary statistics 
together with 95% confidence intervals where applicable. 
 
Descriptive statistics will also be used extensively in figures to visualize the data.  These include 
but are not limited to mean (SE) plots against time, waterfall plots for individual changes at a 
specific time point, vertical bar plots showing percentages of participants meeting a specific 
criterion, scatter plots to look at correlations between endpoints or timepoints. 
 
Data will be listed in data listings. 
 
Baseline will be defined as the baseline value taken from the parent study. In some cases, change 
prior to first dose of EDP1815 and change since first dose in this study may also be analyzed.      
 
11.2. Definition of Analysis Sets and Defined Data Point Sets 
The following analysis sets will be used in the statistical analyses. 
 
11.2.1. Participant Analysis Sets 
Enrolled set: The enrolled set will consist of all participants who sign the ICF. 
 
Full analysis set (FAS): The FAS set will consist of all participants who receive any IMP under 
this protocol.  
 
Other parent study specific analysis sets may also be used in interim analyses which will be defined 
by the subset of participants from the FAS who were previously enrolled from the specified parent 
study or studies. 
11.2.2. Defined Data Point Sets 
The following data point sets (DPS) are defined: 
 
DPS1: Consists of all observed data collected following first dose of IMP under this protocol until 
the 28 days after the last dose of IMP. 
 
DPS2: Consists of all observed data collected following first dose of active IMP, either in the 
parent study protocol or this protocol until 28 days after the last dose of IMP under this protocol. 
 


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DPS3: Consists of all observed data collected at a scheduled visit in this protocol. 
 
DPS3a: Is a subset of DPS3 for responder efficacy endpoints only, excluding any data collected 
within 4 weeks after the use of permitted rescue medications or at any time after the use of 
prohibited medications for atopic dermatitis. 
 
DPS3b: Is a subset of DPS3 for responder efficacy endpoints only, where data collected within 4 
weeks after the use of permitted rescue medications, at any time after the use of prohibited 
medications for atopic dermatitis, or at scheduled endpoints after withdrawal from treatment due 
to treatment-failure related reasons (related AEs, lack of efficacy, requirement for alternate 
psoriasis therapy) will be replaced by ‘non-responder’ . 
 
DPS4: Consists of all observed data collected at a schedule visit in this study or the parent study 
for participants who enter this study.  
 
DPS4a: Is a subset of DPS4, excluding any data collected within 4 weeks after the use of permitted 
rescue medications for atopic dermatitis or at any time after the use of prohibited medications for 
atopic dermatitis. 
 
DPS4b: Is a subset of DPS4 for responder endpoints only, where data collected within 4 weeks 
after the use of permitted rescue medications for atopic dermatitis, at any time after the use of 
prohibited medications for atopic dermatitis, or at scheduled endpoints after withdrawal from 
treatment due to treatment-failure related reasons (related AEs, lack of efficacy, requirement for 
alternate psoriasis therapy) will be replaced by ‘non-responder’. 
 
The FAS with DPS1 and DPS2 will be used to estimate the primary estimands around adverse 
events, together with estimands based on efficacy count endpoints looking at use of rescue 
medications. 
 
The FAS with DPS3b and DPS4b will be used to estimate efficacy responder endpoints.  In 
addition DPS3, DPS3a, DPS4 and DPS4a will be used to estimate supplementary estimands for 
the key efficacy responder endpoints. 
 
The FAS with DPS3a and DPS4a  will be used to estimate efficacy continuous endpoints where 
data is collected at specific timepoints.  
 
The FAS with DPS3 and DPS4 will be used to estimate safety endpoints where data is collected at 
specific timepoints. 
 
The parent study-specific populations will be used instead of the FAS for interim analyses based 
on participants taken from a specific study or studies. 
 
11.3. Estimands and Intercurrent Events 
 


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11.3.1. Primary Estimand of the Primary Objective 
Population: The FAS will be used for all primary estimands.  Note that for interim analyses, a 
parent study specific analysis set may be used in place of the FAS. 
 
The primary safety variables will be the incidence and rate per 100 patient-years of TEAEs.  
 
Safety data will be reported for two periods: (1) the period beginning with the first dose of active 
IMP in this study (2) the period beginning with the first dose of active IMP across this study and 
the parent study. 
 
Subgroups of TEAEs will be evaluated as follows: 
• All TEAEs 
• TEAEs of Grade 2 or above 
• TEAEs of Grade 3 or above 
• Serious TEAEs 
• Fatal TEAEs 
• TEAEs causing discontinuation of study drug 
• Study drug related TEAEs Study (defined by an investigator assessment of possible, 
probable, or definite relationship to IMP) 
• Study drug related TEAEs of Grade 2 or above 
• Study drug related TEAEs of Grade 3 or above 
• Study drug related serious TEAEs 
• Study drug related fatal TEAEs 
• Study drug related TEAEs causing discontinuation of study drug 
 
Population summary measure of interest: For the endpoints looking only at the period defined by 
this study only, the incidence and rate per 100 patient-years of each category of TEAEs. For the 
endpoints looking at the period defined since first dose of active IMP by either in  this study and 
the relevant parent study, the rate per 100 patient-years of each category of TEAEs by treatment 
group. 
 
Treatment groups: For the endpoints looking only at the period defined by this study only, the data 
will be summarized by daily EDP1815 dose for this study, giving three treatment groups in total: 
• 1.6x1011 total cells per day of EDP1815 (TCPD-1815) 
• 6.4x1011 TCPD-1815  
• 8.0x1010 TCPD-1815 
 
For the endpoints looking at the period defined since first dose of active IMP either in  this study 
or the relevant parent study, data will be summarized by active daily dose across both studies, 
giving four treatment groups in total:  
• 1.6x1011 TCPD-1815  
• 6.4x1011 TCPD-1815  
• 6.4x1011 to 1.6x1011 TCPD-1815 
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Note that the 6.4x1011 TCPD-1815 group includes patients from the parent study who received 
this TCPD under both QD and BD dosing schedules. Pooling these patients together assumes 
safety for these two schedules is similar.  If emerging results from the parent studies violate that 
assumption, then these subgroups may be analyzed separately. 
 
Strategies for intercurrent events:  
• Discontinuation of treatment will use a composite strategy as the ‘treatment emergent’ 
includes the discontinuation of treatment as part of the definition 
• The use of other medications (including permitted rescue therapies), non-compliance with 
study drug and any deviations from protocol will use a treatment policy strategy in which 
all data is used regardless of the intercurrent event 
 
11.3.2. Secondary Efficacy Estimands 
Population: The FAS will be used for all secondary estimands. Note that for interim analyses, a 
parent study specific analysis set may be used in place of the FAS. 
 
Population summary measure of interest:  
• For continuous endpoints, the mean at each scheduled visit will be used 
• For responder endpoints, the percentage of participants with the relevant response will be 
used 
• For rate endpoints, the number of events per patient-year will be used 
 
Treatment groups: Efficacy data will be summarized by daily dose in this study and the parent 
study, giving a total of seven treatment groups as follows: 
• 1.6x1011 TCPD-1815 in this study, Placebo in parent study  
• 1.6x1011 TCPD-1815 in this study, 1.6x1011 TCPD-1815 in parent study 
• 1.6x1011 TCPD-1815 in this study, 6.4x1011 TCPD-1815 in parent study 
• 6.4x1011 TCPD-1815 in this study, Placebo in parent study 
• 6.4x1011 TCPD-1815 in this study, 6.4x1011 TCPD-1815 in parent study 
• 8.0x1010 TCPD-1815 in this study, Placebo in parent study 
• 8.0x1010 TCPD-1815 in this study, 8.0x1010 TCPD-1815 in parent study 
Further treatment group combinations may be added if additional parent studies feed into this 
protocol.   
 
As with the safety estimands, the 6.4x1011 TCPD-1815 group for the parent study treatment arm 
includes patients from the parent study who received this TCPD under both QD and BD dosing 
schedules. Pooling these patients together assumes efficacy for these two schedules is similar.  If 
emerging results from the parent studies violate that assumption, then these subgroups of patients 
may be analyzed separately. 
 
Strategies for intercurrent events for response endpoints:   
• Use of rescue medications within 4 weeks,  use at any time of other prohibited 
medications for atopic dermatitis, and discontinuation of treatment for treatment failure-
related reasons (related AEs, lack of efficacy, requirement for alternate psoriasis therapy), 
will be considered using 3 separate strategies. The composite strategy will be used for all 
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strategy and the while on treatment strategy will be used for key secondary response 
endpoints (as indicated in Table 11-1: Secondary Efficacy Estimands)  
 
o Treatment policy: including all data collected regardless of use of rescue 
medications or other prohibited medications for atopic dermatitis 
o While on treatment: excluding all data collected within 4 weeks after use of rescue 
medications or at any time after use of other prohibited medications for atopic 
dermatitis 
o Composite strategy: replacing data all data collected within 4 weeks after use of 
rescue medications, at any time after use of other prohibited medications for atopic 
dermatitis, or at scheduled visits after treatment discontinuation for treatment-
related reasons. Response endpoints will replace such data with ‘non-response’. 
• Discontinuation of treatment for reasons not related to treatment-failure: a treatment policy 
strategy will be followed in that there will be no window for days since discontinuation 
applied to exclude or change data.  However, it should be noted that participants will be 
withdrawn from the study following discontinuation of treatment and as such it is expected 
that data collected at the scheduled visits will only include participants who are on 
treatment (or very recently discontinued) with the exception of those visits specifically 
scheduled to occur 4 and 12 weeks after last dose.  
• Non-compliance with study drug and any deviations from protocol not relating to the use 
of other treatments for atopic dermatitis will use a treatment policy strategy in which all 
data is used regardless of the intercurrent event. 
 
Strategies for intercurrent events for continuous endpoints:  
• Discontinuation of treatment for any reason: a treatment policy strategy will be followed 
in that there will be no window for days since discontinuation applied to exclude or change 
data.  However, it should be noted that participants will be withdrawn from the study 
following discontinuation of treatment and as such it is expected that data collected at the 
scheduled visits will only include participants who are on treatment (or very recently 
discontinued) with the exception of those visits specifically scheduled to occur 4 and 12 
weeks after last dose. 
• Non-compliance with study drug and any deviations from protocol not relating to the use 
of other treatments for atopic dermatitis will use a treatment policy strategy in which all 
data is used regardless of the intercurrent event 
 
Strategies for intercurrent events for rate endpoints looking at rescue medication will use the same 
approach as specified for the primary estimands. 
 
Endpoints:  Table 11-1 shows the secondary efficacy endpoints defined for this study.  All response 
and continuous endpoints will be summarized at all scheduled visits in both this study and the 
relevant parent study. Count endpoints will be reported for two periods: (1) the period beginning 
with the first dose of active IMP in this study (2) the period beginning with the first dose of active 
IMP across this study and the parent study.  
 




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Time to first achievement 
of sustained EASI-50  
achieving response 
at each visit 
 
Treatment policy: All data collected will be 
used regardless of intercurrent events of 
treatment discontinuation, treatment 
compliance or deviations from the protocol. 
Change from baseline in 
ADCT score 
DPS3 and 
DPS4 
Mean change from 
baseline at each 
scheduled visit 
Treatment policy for all possible intercurrent 
events (all data included as collected at 
scheduled visits) 
Change and percentage 
change from baseline in 
the each of the four body-
region scores of the EASI 
DPS3b and 
DPS4b 
Mean change from 
baseline at each 
scheduled visit 
Composite: Use of rescue medications 
within 4 weeks and use at any time of other 
prohibited medications for atopic dermatitis 
will be imputed using the last available off-
rescue value carried forward. 
 
Treatment policy: All data collected will be 
used regardless of intercurrent events of 
treatment discontinuation, treatment 
compliance or deviations from the protocol. 
Achievement of 50% 
reduction in each of the 
four body region scores of 
the EASI1 
DPS3b and 
DPS4b 
Percentage of 
participants 
achieving response 
at each visit 
Composite: Use of rescue medications 
within 4 weeks and use at any time of other 
prohibited medications for atopic dermatitis 
will be considered as non-response. 
 
Treatment policy: All data collected will be 
used regardless of intercurrent events of 
treatment discontinuation, treatment 
compliance or deviations from the protocol. 
Change in response states 
from Day -1 to Weeks 8, 
16, 24 and 36. 
Response states will be 
defined using the EASI 
score percentage change 
from baseline with 
categories for:  
≥25% increase,  
no change (<25% increase 
to <25% decrease),  
25% to <50% decrease,  
50% to <75% decrease,  
75% to <90% decrease,  
≥90% decrease 
DPS3b 
Percentage of 
participants with 
each change in 
response state 
Composite: Use of rescue medications 
within 4 weeks and use at any time of other 
prohibited medications for atopic dermatitis 
have response state calculated using the last 
off-rescue value carried forward. 
 
Treatment policy: All data collected will be 
used regardless of intercurrent events of 
treatment discontinuation, treatment 
compliance or deviations from the protocol 
Absolute change from 
baseline in PP-NRS and 
SD-NRS scores. 
DPS1 and 
DPS2 
Mean change from 
baseline at each 
study day 
Composite: Use of rescue medications 
within 4 weeks and use at any time of other 
prohibited medications for atopic dermatitis 
have response state imputed using the last 
off-rescue value carried forward. 
 
Treatment policy: All data collected will be 
used regardless of intercurrent events of 
treatment discontinuation, treatment 
compliance or deviations from the protocol 
Changes from baseline in 
serum immune protein 
markers including IgE and 
DPS3 and 
DPS4 
Mean change from 
baseline at each 
scheduled visit 
Treatment policy for all possible intercurrent 
events (all data included as collected at 
scheduled visits) 




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study specific analysis performed after all participants from each parent study have completed this 
study. 
 
11.8. Determination of Sample Size 
 
The sample size of the study will be determined by the number of participants who enroll from 
qualifying atopic dermatitis parent studies with EDP1815. 
 
 
 
 


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12. ETHICS AND REGULATORY REQUIREMENTS 
 
12.1. Informed Consent 
Participant’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki. 
 
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the participant in both oral and written form by the Investigator (or 
designee).  Each participant will have the opportunity to discuss the study and its alternatives with 
the Investigator. 
 
Prior to participation in the study, the Informed Consent Form (ICF) should be signed and 
personally dated by the participant, or his/her legal representative, and by the person who 
conducted the informed consent discussion (Investigator or medically licensed Sub-Investigator). 
The participant or his/her legal representative must receive a copy of the signed and dated ICF. As 
part of the consent process, each participant must consent to direct access to his/her medical 
records for study-related monitoring, auditing, IRB/IEC review, and regulatory inspection. 
 
If the ICF is amended during the study, the Investigator (or the Sponsor, if applicable) must follow 
all applicable regulatory requirements pertaining to the approval of the amended Informed Consent 
form by the IRB/IEC and use of the amended form. 
 
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act Authorization form. 
 
The participant may withdraw his/her consent to participate in the study at any time. A participant 
is considered as enrolled in the study when he/she has signed the ICF. Study specific procedures 
may not be performed for a given participant, without having obtained his/her written consent to 
participate in the study. 
 
12.2. Participant Identification Cards 
Upon signing the Informed Consent and Assent Form(s) (as applicable), the participant or legal 
representative will be provided with a participant identification card in the language of the 
participant. The Investigator will fill in the participant identifying information and medical 
emergency contact information. The Investigator will instruct the participant to keep the card with 
him/her at all times. 
 
12.3. Institutional Review Boards and Independent Ethics Committees 
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
ICH-GCP, and in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki. 
 
The Investigator and Sponsor or their designee will confirm that an appropriately constituted 
IRB/IEC that complies with the requirements of the current ICH-GCP version or applicable 
country specific regulations will be responsible for the initial and continuing review and approval 


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of the clinical study. Prior to initiation of the study, the Investigator or the Sponsor or their designee 
will forward copies of the protocol, Informed Consent form, Investigator’s Brochure, 
Investigator’s curriculum vitae (if applicable), advertisement (if applicable), and all 
other -participant related documents to be used for the study to the IRB/IEC for its review and 
approval. 
 
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol filed in the ISF. 
 
The Investigator will also promptly report to the IRB/IEC all changes in the study, all unanticipated 
problems involving risks to human participants or others, and any protocol deviations, to eliminate 
immediate hazards to participants. 
 
The Investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the participants. For 
minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the Investigator to obtain an expedited review by the IRB/IEC as 
allowed. 
 
As part of the IRB/IEC requirements for continuing review of approved studies, the Investigator 
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of participant risk involved, but no less than 
once per year. The Investigator should provide a final report to the IRB/IEC following study 
completion. 
 
The Sponsor (or its representative) will communicate safety information to the appropriate 
regulatory authorities and all active investigators in accordance with applicable regulatory 
requirements. The appropriate IRB/IEC will also be informed by the Investigator or the Sponsor, 
as specified by the applicable regulatory requirements in each concerned country. Where 
applicable, investigators are to provide the sponsor (or its representative) with evidence of such 
IRB/IEC notification. 
 
12.4. Participant Privacy 
The Sponsor or their designee will protect the participant’s confidentiality. Throughout this study, 
all data forwarded to the Sponsor or their designee, will be identified only by the participant 
number assigned at the Day -1 Visit.  All personal data collected related to participants, 
Investigators, or any person involved in the study, which may be included in the Sponsor’s 
databases, shall be treated in accordance with applicable data protection law. 
 
The Investigator agrees that representatives of the Sponsor, its designee, representatives of the 
relevant IRB/IEC, or representatives of regulatory authorities will be allowed to review that 
portion of the participant’s primary medical records that directly concerns this study (including, 
but not limited to, laboratory test result reports, ECG reports, admission/discharge summaries for 
hospital admissions occurring during a participant’s study participation, and autopsy reports for 
deaths occurring during the study). 
 




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13. REFERENCES 
       
de Groot PF, Belzer C, Aydin Ö, et al. Distinct fecal and oral microbiota composition in human 
type 1 diabetes, an observational study. PLoS One. 2017;12(12):e0188475.  
 
Atkinson. (2004). Retrieved from https://www.iqvia.com/-/media/iqvia/pdfs/landing-
pages/treatment-satisfaction/atkinson-2004-tsqm-14-
development.pdf?la=en&hash=D4451E03980A36AEEF0895D6B6985DA3&_=1615920
176681  
 
Basra. (2015). Retrieved from https://pubmed.ncbi.nlm.nih.gov/25613671/  
 
Bieber. (2010). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883413/ 
 
Bieber. (2010). Atopic Dermatitis. Ann Dermatol., 22(2):125-137. 
 
Dermatitis, S. s. (1993). Severity Scoring of Atopic Dermatitis: The SCORAD Index. 
Dermatology, 186, 23-31. 
 
Dias-Barbosa, C., Matos, R., & Vernon, M. (2020). Content validity of a sleep numerical rating 
scale and a sleep diary in adults and adolescents with moderate-to-severe atopic 
dermatitis. J Patient Rep Outcomes, 4, 100. 
 
EASI. (2017 Jan). Eczema Area and Severity Index (EASI) Guidance. Version 3.0. 
 
Eczema, H. f. (n.d.). Retrieved from http://www.homeforeczema.org/research/easi-for-clinical-
signs.aspx  
 
EMEA. (2002 Jul). CPMP/ICH/135/95 Note for guidance on Good Clinical Practice [Section 
4.9.5]. 
 
Finlay AY, K. G. (1994). Dermatology Life Quality Index (DLQI): a simple practical measure 
for routine clinical use. . Clin Exp Dermatol. , 19, 210-216. 
 
Indra. (2013). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038411/ 
 
Katoh. (2019). Retrieved from https://onlinelibrary.wiley.com/doi/full/10.1111/1346-8138.15090 
 
Kiebert. (2002). Retrieved from https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-
4362.2002.01436.x?sid=nlm%3Apubmed  
 
Lee. (2016). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773205/ 
 
Leshem, Y. A., Bissonnette, R., Paul, C., Silverberg, J. I., Irvine, A. D., Paller, A. S., . . . 
Guttman-Yassky, E. (2019). Optimization of placebo use in clinical trials with systemic 


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16 May 2022 
 
 
 
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treatments for atopic dermatitis: an International Eczema Council survey-based position 
statement. Journal of the European Academy of Dermatology and Venereology, 33(5), 
807-815. Retrieved from Reference: Optimization of placebo use in clinical trials with 
systemic 
 
Mangalam, A., Shahi, S., & Luckey, D. (017). Human gut-derived commensal bacteria suppress 
CNS inflammatory and demyelinating disease. Cell Rep, 20(6):1269-77. 
 
Marietta, E., Murray, J., & Luckey, D. (2016). Marietta EV, Murray JA, Luckey DH, et al. 
Human gut-derived Prevotella histicola suppresses inflammatory arthritis in humanized 
mice. Arthritis Rheumatol. 68(12):2878-88. 
 
National Eczema Association. (2016). https://nationaleczema.org/in-your-words-survey-series. 
 
Pariser. (2020, January 13). Evaluating patient-perceived control of atopic dermatits; design, 
validation, and scoring of the Atopic Dermatitis Control Tool (ADCT). Curr Med Res 
Opin., 367-376. 
 
Phan. (2011). Ref: Assessment of Pruritus Intensity: Prospective Study on Validity and 
Reliability of the Visual Analogue Scale, Numerical Rating Scale and Verbal Rating 
Scale in 471 Patients with Chronic Pruritus.  
 
Renert-Yuval. (2021). Retrieved from 
https://www.sciencedirect.com/science/article/pii/S0091674921000968  
 
Schatz. (2006). Retrieved from https://www.jacionline.org/article/S0091-6749(06)00174-
6/fulltext  
 
Schram, M., Spuls, P., Leeflang, M., Lindeboom, R., Bos, J., & Schmitt, J. (2011). EASI, 
(objective) SCORAD and POEM for atopic eczema: Responsiveness and minimal 
clinically important difference. Allergy, 67(1);99-106. 
 
Simpson. (2012). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671606/ 
 
Simpson E, B. R. (2020 Sep). The Validated Investigator Global Assessment for Atopic 
Dermatitis (vIGA-AD): The development and reliability testing of a novel clinical 
outcome measurement instrument for the severity of atopic dermatitis. J Am Acad 
Dermatiol., 83(3), 839-846. 
 
Snaith. (2003). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC183845/  
 
Suh. (2020). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457338/ 
 
Vandeputte, D., Kathagen, G., & D'hoe, K. (2017). Quantitative microbiome profiling links gut 
community variation to microbial load. Nature, 551:507-11. 


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Ware J, K. M. (1996). A 12-Item Short-Form Health Survey: construction of scales and 
preliminary tests of reliability and validity. Med Care. 1996. 34; 3:220-33. Med. Care, 
220-233. 
 
Yosipovitch, G., Reaney, M., Mastey, V., Eckert, L., Abbe, A., Nelson, L., . . . Gadkari, A. 
(2019). Peak Pruritus Numerical Rating Scale: psychometric validation and responder 
definition for assessing itch in moderate-to-severe atopic dermatitis. The British Journal 
of Dermatology, 181(4), 761-769. 
 
 
 


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14. APPENDICES 
14.1. Classification of Potency of Topical Corticosteroids 
 
 


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14.2. Contraceptive Guidance and Collection of Pregnancy Information 
Definitions 
Woman of Child-Bearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
 
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
• Documented bilateral tubal ligation 
 
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
 
3. Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months prior to the Day -1 
Visit without an alternative medical cause.  In the absence of 12 months of 
amenorrhea, postmenopausal women will be assumed to be WOCBP and will need 
to follow contraceptive guidance and have pregnancy tests performed throughout 
the course of the study per the Schedule of Activities (SOA). 
 
• Females on HRT and whose menopausal status is in doubt will be required to use 
one of the non-estrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study.  
 
Contraception Guidance 
 
Male participants with a female partner of child-bearing potential must either 
• Be abstinent from penile-vaginal intercourse as their usual and preferred lifestyle 
(abstinent on a long term and persistent basis) and agree to remain abstinent 
 
• Use a male condom during each episode of penile penetration during their 
participation in the study and for 90 days after the last dose of IMP.  
 
• Have a confirmed vasectomy where the absence of sperm has been confirmed 
 
In addition, all male participants must refrain from donating sperm for the duration of the study 
and for at least 90 days following their final visit. 


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Female participants 
Female participants of child-bearing potential are eligible to participate if they agree to use a highly 
effective method of contraception consistently and correctly as described in the table below. 
Table 14-1: 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a  
Failure rate of < 1% per year when used consistently and correctly.  
Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulationb. 
• Oral  
• Intravaginal  
• Transdermal  
Progestogen only hormonal contraception associated with inhibition of ovulation 
• Oral  
• Injectable  
Highly Effective Methods That Are User Independent a  
• Implantable progestogen only hormonal contraception associated with inhibition of 
ovulationb. 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
Vasectomised partner  
A verified vasectomised partner is a highly effective contraception method provided that the 
partner is the sole male sexual partner of the WOCBP, and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used.  
Sexual abstinence  
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention, 
including at least 1 complete menstrual cycle (cycle (≥ 30 days) for women and 90 days for 
men post last dose. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the study and the preferred and usual lifestyle of the participant.  
NOTES:  
a) Typical use failure rates may differ from those when used consistently and correctly. Use 
should be consistent with local regulations regarding the use of contraceptive methods for 
participants participating in clinical studies.  
b) Hormonal contraception may be susceptible to interaction with the study intervention, 
which may reduce the efficacy of the contraceptive method. In this case, a highly effective 
method of contraception plus condoms should be utilized during their participation in the 
study up to and including at least 1 complete menstrual cycle (≥ 30 days) for women and 
90 days for men post last dose.  


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Pregnancy Testing 
• WOCBP should only be included after a confirmed menstrual period and a negative 
pregnancy test. 
• Pregnancy testing is required at the Day -1 visit.  
• Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected. 
 
Collection of Pregnancy Information 
Male participants with partners who become pregnant  
• The Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. This 
applies to all male participants who receive EDP1815. 
 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 24 hours of learning of the partner’s pregnancy. The female 
partner will also be followed to determine the outcome of the pregnancy. Information on 
the status of the mother and child will be forwarded to the Sponsor. Generally, the follow-
up will be no longer than 8 weeks following the estimated delivery date. Any termination 
of the pregnancy will be reported regardless of foetal status (presence or absence of 
anomalies) or indication for the procedure.  
Female participants who become pregnant  
• The investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. Information will be recorded on the 
appropriate form and submitted to the Sponsor within 24 hours of learning of a participant's 
pregnancy. The participant will be followed to determine the outcome of the pregnancy. 
The investigator will collect follow-up information on the participant and the neonate, and 
the information will be forwarded to the Sponsor. Generally, follow-up will not be required 
for longer than 6 to 8 weeks beyond the estimated delivery date. Any termination of 
pregnancy will be reported, regardless of foetal status (presence or absence of anomalies) 
or indication for the procedure. 
 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication 
or elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous 
abortion is always considered to be an SAE and will be reported as such. Any post-study 
pregnancy related- SAE considered reasonably related to the study intervention by the 
Investigator will be reported to the Sponsor as described in Section 9.5 Reporting Serious 
Adverse Events. While the Investigator is not obligated to actively seek this information 
in former study participants, he or she may learn of an SAE through spontaneous reporting.  
 
• Any female participant who becomes pregnant while participating in the study will 
discontinue study intervention or be withdrawn from the study. 


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14.3. EDP1815 COVID-19 Risk Assessment 
Antiviral responses are activated rapidly after viral infection in order to control and prevent 
dissemination of the virus. Virus infection results in two general types of immune response. The 
first is a rapid onset innate immune response against the virus, which involves the synthesis of 
Type 1 interferons and the stimulation of Natural Killer (NK) cells. If the infection proceeds 
beyond the first few rounds of viral replication, the innate immune response will trigger the 
adaptive immune response. The adaptive immune response itself has two components, the humoral 
response (the synthesis of virus-specific antibodies by B lymphocytes) and the cell-mediated 
response (the synthesis of specific CD8+ cytotoxic T lymphocytes that kill infected cells). Both of 
these components of the adaptive immune response result also in the production of long-lived 
memory cells that allow for a much more rapid response to a subsequent infection with the same 
virus.  Thus, an immune competent host should be able to mount both an innate and adaptive 
immune response.   
EDP1815 is a single strain of human commensal Prevotella histicola that is being clinically tested 
to treat inflammatory skin diseases such as psoriasis and atopic dermatitis (studies 1815-101, 1815-
201, and 1815-207); in a pharmacodynamic immune challenge study to Keyhole Limpet 
Haemocyanin (KLH) (study 1815-102); and also, to treat the complications of infection with 
COVID-19 (study 1815-204 and 1815-205).  EDP1815 is administered orally and is gut restricted.  
Therefore, EDP1815 exerts its anti-inflammatory effects on peripheral tissue through engagement 
of cells of the intestine, including small intestinal epithelial cells and immune cells in the lamina 
propria.   
EDP1815 has been shown in preclinical mouse inflammation models to reduce antigen-specific T 
cell responses, without impacting: 
• The anti-viral TLR3-mediated Type 1 interferon (alpha and beta) response  
• Interferon-gamma production by T cells and NK cells 
• Immune cell subsets (absolute number and percentage), including CD8 T lymphocytes, B 
lymphocytes, and myeloid lineage cells 
• The antigen-specific antibody responses (IgM and IgG) 
In human immune cell in vitro assays, EDP1815 did not alter the ability of human dendritic cells 
to induce the production of interferon-gamma from memory CD8 T cells in response to a viral 
peptide pool (Cytomegalovirus, Epstein-Bar virus, and Influenza virus), an important component 
of an anti-viral response. 
And clinically, treatment with EDP1815 was shown to reduce specific inflammatory myeloid cell 
cytokines such as IL-6 and IL-8, while not affecting levels of T cell cytokines such as interferon-
gamma, produced by circulating peripheral blood mononuclear cells.   
Taken together, the data demonstrate that treatment with EDP1815 does not result in general 
immuno-suppression of multiple immune pathways but is effective through a selective restoration 
of immune homeostasis. 
 


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TLR3-mediated induction of Type 1 interferons in the KLH delayed-type hypersensitivity model 
Mice were immunized by subcutaneous injection with KLH emulsified with Complete Freund’s 
Adjuvant. On Day 6 after the sensitization, mice were dosed for 3 days with oral EDP1815, or 
dexamethasone given intraperitoneally.  On day 8, mice were challenged by intradermal ear 
injection with KLH. The DTH response was evaluated 24 hours post-challenge. For the ex vivo 
cytokine analysis, spleen cells from treated mice were incubated for 48 hours in vitro and 
stimulated with polyinosinic-polycytidylic acid (poly I:C), a molecule that mimics viral double-
strained RNA, and a potent ligand for Toll-like receptor 3, which induces interferon-alpha and 
interferon-beta from immune cells. 
 
Results: Three days of dosing with EDP1815 or dexamethasone significantly inhibited ear 
inflammation. In addition, while dexamethasone significantly inhibited the production of 
interferon-alpha and interferon-beta in the spleen cell stimulation assay, oral EDP1815 had no 
impact on these Type 1 interferons. This demonstrates that EDP1815 selectively inhibits tissue 
inflammation while preserving protective Type 1 interferon responses. 
 
  
 
 
 


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Interferon-gamma production by lymphocytes in vivo 
 
In the same study, spleen cells were restimulated with PMA and ionomycin.  PMA activates 
protein kinase C, while ionomycin is a calcium ionophore, and stimulation with these compounds 
bypasses the T cell membrane receptor complex and will lead to activation of several intracellular 
signaling pathways, resulting in T cell activation and production of a variety of 
cytokines.  Stimulation with PMA/ionomycin induced robust production of interferon-gamma 
from spleen cells, and treatment with EDP1815 or dexamethasone did not reduce the production 
of interferon-gamma, demonstrating that the Cytotoxic CD8 T cell/NK axis of immunity was 
intact. 
 
 
  
 
Immune cell subsets quantification after EDP1815 dosing 
 
In other DTH studies, immune cell numbers in lymphoid tissues were measured.  Mesenteric 
lymph nodes which drain the small intestine were removed at the end of a delayed-type 
hypersensitivity study, performed as described above.  Single cell suspensions were made from 
the lymph nodes, stained using antibodies against cell surface markers, and quantified by flow 
cytometry.  Treatment with EDP1815 for 5 days did not alter any immune cell subsets, including 
T cells, NK cells, B cells, neutrophils, macrophages, and monocytes in the lymph nodes. 
 
 
 
 
  
 
 


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KLH-specific antibody response 
 
Antibodies are one of the essential features of antigen-triggered adaptive immunity against viruses 
and requires a coordinated response between antigen-presenting cells such as dendritic cells, 
antigen-specific helper T cells, and antigen-specific B cells.  Although treatment with EDP1815 
causes a marked reduction in peripheral inflammation in the KLH delayed-type hypersensitivity 
model, no effect on KLH-specific IgM or IgG has been observed in either preclinical models or in 
a clinical study (data not shown). 
 
In vitro assay co-culture with human dendritic cells and CD8 T cells  
 
An in vitro assay with primary human DCs and autologous CD8+ T cells was carried out to 
measure the capacity of EDP1815 to modulate antigen-specific CD8+ T cell responses. Briefly, 
primary human DCs from 3 healthy donors were differentiated in vitro for 7 days. To assess the 
immuno-modulatory properties of EDP1815, DCs were incubated with EDP1815 or ES880, a 
different Prevotella strain that does not exhibit anti-inflammatory activity, for 24 hours in vitro. 
After 24 hours of microbe conditioning, microbes were removed from the DC culture and 
autologous human CD8+ T cells and CEF Class I peptide pool was added. The CEF peptide pool 
is composed of peptides from Cytomegalovirus, Epstein Bar virus, and Influenza virus, pathogens 
to which the majority of the human population has been exposed. After 24 hours of stimulation 
with CEF peptide, DC-CD8+ T cell supernatants were collected and IFNγ was measured. When 
human DCs were incubated with EDP1815, the IFNγ response to CEF was not affected (neither 
enhanced nor decreased) compared to the DC-CD8 T cell co-culture control.  In contrast, 
incubation with ES880 led to increased production of IFNγ. 


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Conclusion 
 
The combination of in vitro, in vivo, and ex vivo data demonstrate that EDP1815 does not broadly 
impair either innate or adaptive immune responses.  EDP1815 is orally delivered and gut restricted, 
and therefore its effect is exerted through local interactions with cells of the small intestine, which 
are then translated from the gut to the periphery to resolve inflammation.  Anti-viral responses 
such as cytotoxic T cell production of interferon-gamma, innate anti-viral production of interferon-
alpha and interferon-beta, and the generation of high affinity antibodies are all preserved after 
treatment with EDP1815. 
 
The data demonstrate that treatment with EDP1815 results in resolution of multiple pathways of 
inflammation without leading to immunosuppression of the host response. 
 
 


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14.4. Toxicity Grading Scale 
The following scales come from the FDA Guidance for Industry Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, September 2007. 
 
Temperature Adverse Event Grading Scale 
 
Vitals Signs* 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Potentially 
Life 
Threatening (Grade 
4) 
Fever (ºC)** 
          (ºF)** 
38.0 – 38.4 
100.4 – 101.1 
38.5 – 38.9 
101.2 – 102.0 
39.0 – 40 
102.1 - 104 
> 40  
>104 
 
Laboratory Results Adverse Event Grading Scale 


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15. DECLARATION AND SIGNATURE OF INVESTIGATOR 
 
I confirm that I have carefully read and understood this protocol and agree to conduct this clinical 
study as outlined in this protocol, according to current Good Clinical Practice (GCP) and local 
laws and requirements. 
 
I will ensure that all Sub-Investigators and other staff members read and understand all aspects of 
this protocol. 
 
I have received and read all study-related information provided to me. 
 
The objectives and content of this protocol as well as the results deriving from it will be treated 
confidentially, and will not be made available to third parties without prior authorization by the 
Sponsor, Evelo Biosciences, Inc. 
 
All rights of publication of the results reside with the Sponsor, Evelo Biosciences, Inc, unless other 
agreements were made in a separate contract. 
 
 
Signature of Investigator 
Date 
Investigator Name 
Investigator Title 
Name of Facility 
Location of Facility (City) 
 
 
 






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4.7.1 Dose Rationale  
Additional detail provided on the 
dose rationale.  
 
Clarification of dose rationale.  
9.9 Study Halting Criteria  
Halting language amended 
Amended 
per 
the 
FDA’s 
recommendation. 
10.2.1 Definition of Source Data 
The following bolded, underlined 
text added to this guidance: 
 
The 
following 
data 
will 
be 
considered as electronic source and 
therefore, will not be recorded 
directly into the EDC and will not 
appear 
in 
a 
separate 
source 
document as defined above, unless 
there is a circumstance, such as a 
global power outage, making it 
difficult for site staff to collect this 
data electronically. Any information 
about a participant that is collected 
during this study will remain 
secured and confidential and will be 
handled per applicable regulations 
(i.e., data collected via mobile 
applications). 
 
Text added to ensure that data is not 
missed and is collected at a 
minimum via paper when electronic 
means are not possible due to 
unforeseen circumstances. 
11. Statistics  
Additional detail added to the 
definitions of data points sets used in 
the efficacy estimands, and to the 
specifications 
of 
the 
treatment 
groupings 
used 
in 
the 
summarization of the safety and 
efficacy estimands. 
 
Amended per the FDA’s request for 
clarification. 
14.3 Contraceptive Guidance and 
Collection 
of 
Pregnancy 
Information 
Further clarification provided  that 
women with documented bilateral 
tubal ligation are not considered 
WOCBP and may be considered for 
enrollment in the study without the 
use of additional contraception. 
 
Amended to align with parent study.   
  



SAP_001.pdf: 
S T A TI S TI C A L A N A L Y SI S P L A N  (S A P ) 
 
 
N C T 0 5 4 3 9 9 4 1  
 
 
A L O N G -T E R M E X T E N SI O N T RI A L I N P A R TI CI P A N T S WI T H A T O PI C 
D E R M A TI TI S W H O P A R TI CI P A T E D I N P R E VI O U S P H A S E 2 A N D 3 
E D P 1 8 1 5 T RI A L S  
 
 
S A P  E D P 1 8 1 5 -2 0 8  
V E R SI O N  2 . 0 / 0 7 J U N E 2 0 2 3  


St atistic al A n alysis Pl a n   
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P a g e 1  of 7 5  
 
S T A TI S TI C AL A N AL Y SI S PL A N  
 
Pr ot oc ol: E D P 1 8 1 5 -2 0 8  
Pr ot oc ol V ersi o n: V 4 . 0 1 6 M A Y 2 0 2 2  
 
A L o n g -T er m Ext e nsi o n Tri al i n P artici p a nts wit h At o pic D er m atitis w h o 
P artici p at e d i n Pr e vi o us P h as e 2 a n d P h as e 3 E D P 1 8 1 5 Tri als  
 
S A P/ A m e n d m e nt N u m b er   
D at e  
Fi n al  S A P  v 1. 0  
1 6 J a n  2 0 2 3  
Fi n al  S A P  v 2. 0 
0 7 J u n  2 0 2 3  
 
 
 
 
 
Pr e p ar e d f or:  
E v el o Bi osci e nc es I nc.  
 
 
Pr e p ar e d b y:  
 
 
 
 
 
 
 
 
A p pr o v e d by  
Si g n at ur e  
D at e  
 
Cli nic al L e a d,  
Ev el o Bi osci e nc es I nc.  
 
 
Dir ect or of St atistics,  
Ev el o Bi osci e nc es I nc.  
 
 
L e a d St atistici a n,        
 
 


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1  
T a bl e of C o nt e nts  
1   
T a bl e of C o nt e nts  ............................................................................................................................ 2  
2   
A b br evi ati o ns a n d D efi niti o ns ......................................................................................................... 6  
3   
I ntr o d ucti o n .................................................................................................................................... 8  
4   
St u dy O bj ecti v es a n d E n d p oi nts  ..................................................................................................... 8  
4. 1  
St u dy O bj ecti v es  ................................................................................................................... 8  
4. 2  
E n d p oi nts  .............................................................................................................................. 8  
5   
St u dy M et h o ds  .............................................................................................................................. 1 0  
5. 1  
G e n er al St u dy D esi g n a n d Pl a n  ........................................................................................... 1 0  
5. 2  
R a n d o mis ati o n a n d Bli n di n g  ............................................................................................... 1 1  
5. 3  
D eriv e d v ari a bl es  ................................................................................................................ 1 2  
5. 3. 1  
G e n er al  ................................................................................................................... 1 2  
5. 3. 2  
D e m o gr a p hic a n d  B ac k gr o u n d D at a  ...................................................................... 1 2  
5. 3. 3  
Effic ac y  ................................................................................................................... 1 5  
5. 3. 4  
S af et y ...................................................................................................................... 1 7  
6   
S a m pl e Siz e  ................................................................................................................................... 1 8  
7   
G e n er al C o nsi d er ati o ns  ................................................................................................................. 1 8  
7. 1  
A n al ysis P o p ul ati o ns  ........................................................................................................... 1 8  
7. 1. 1  
P artici p a nt A n al ysis P o p ul ati o ns  ............................................................................ 1 8  
7. 1. 2  
D efi n e d D at a P oi nt S ets  ......................................................................................... 1 9  
7. 2  
C o v ari at es a n d S u b gr o u ps  .................................................................................................. 2 0  
7. 3  
Missi n g D at a  ........................................................................................................................ 2 0  
7. 3. 1  
P arti al D at es/ Ti m es  ................................................................................................ 2 0  
7. 3. 2  
A dv ers e E v e nt I nf or m ati o n  .................................................................................... 2 1  
7. 4  
St u dy D eli v eri es  .................................................................................................................. 2 1  
7. 4. 1  
E arl y St o p pi n g  ........................................................................................................ 2 1  
7. 4. 2  
P ur p os e of St u dy D eliv eri es  ................................................................................... 2 1  
7. 4. 3  
Pl a n n e d Sc h e d ul e of D eliv eri es  .............................................................................. 2 1  
7. 4. 4  
E n d p oi nts t o b e I ncl u d e d i n t h e St u dy D eli v eri es  .................................................. 2 2  
7. 4. 5  
A dj ust m e nt of C o nfi d e nc e I nt er v als a n d p -v al u es ................................................. 2 2  
7. 4. 6  
Pr act ic al M e as ur es t o Mi ni mis e Bi as ..................................................................... 2 2  
7. 4. 7  
D oc u m e nt ati o n of St u dy D eli v eri es  ....................................................................... 2 2  
7. 5  
M ulti -c e ntr e St u di es ........................................................................................................... 2 2  


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7. 6  
M ulti pl e T esti n g  .................................................................................................................. 2 2  
7. 7  
Visit Wi n d o ws  ..................................................................................................................... 2 3  
8   
S u m m ary of St u dy D at a  ................................................................................................................ 2 3  
8. 1  
E arl y St o p pi n g  ..................................................................................................................... 2 4  
8. 2  
St u dy Dis p ositi o n  ................................................................................................................ 2 5  
8. 3  
Pr ot oc ol D evi ati o ns  ............................................................................................................. 2 5  
8. 4  
D e m o gr a p hic a n d B as eli n e V ari a bl es  ................................................................................. 2 5  
8. 5  
M e dic al Hist ory  ................................................................................................................... 2 6  
8. 6  
Pri or a n d C o nc o mit a nt M e dic ati o ns  ................................................................................... 2 6  
8. 7  
Tr e at m e nt C o m pli a nc e  ....................................................................................................... 2 7  
8. 8  
E m olli e nt C o m pli a nc e  ......................................................................................................... 2 7  
9   
Pri m ar y S af et y A n al ysis  ................................................................................................................. 2 7  
9. 1  
E arl y St o p pi n g  ..................................................................................................................... 2 7  
9. 2  
Pri m ar y Esti m a n d of t h e Pri m ar y O bj ecti v e  ....................................................................... 2 8  
9. 2. 1  
Esti m a n ds  ............................................................................................................... 2 8  
9. 2. 2  
A n al ytic al A p pr o ac h  ............................................................................................... 2 9  
1 0  Effic ac y A n al ys es  ........................................................................................................................... 2 9  
1 0. 1  E arl y St o p pi n g  ..................................................................................................................... 2 9  
1 0. 2  S ec o n d ar y Effic ac y A n alysis  ................................................................................................ 3 0  
1 0. 2. 1  R es p o n d er A n al ysis  ................................................................................................ 3 0  
1 0. 2. 2  C o nti n u o us V ari a bl es A n alysis  ............................................................................... 3 2  
1 0. 2. 3  R at e V ari a bl es A n al y sis .......................................................................................... 3 3  
1 0. 3  Ex pl or at ory Effic ac y A n alysis  .............................................................................................. 3 4  
1 0. 3. 1  Ti m e t o Ev e nt A n al ysis  ........................................................................................... 3 4  
1 0. 3. 2  C o nti n u o us V ari a bl es A n alysis  ............................................................................... 3 5  
1 0. 3. 3  R es p o n d er A n al ysis  ................................................................................................ 3 6  
1 1  S af et y A n alys es  ............................................................................................................................. 3 7  
1 1. 1  E arl y St o p pi n g  ..................................................................................................................... 3 8  
1 1. 2  Ext e nt of Ex p os ur e  .............................................................................................................. 3 8  
1 1. 3  A dv ers e E v e nts  .................................................................................................................... 3 8  
1 1. 4  D e at hs, S eri o us A dv ers e E v e nts a n d ot h er Si g nific a nt A dv ers e E v e nts  .............................. 3 9  
1 1. 5  Pr e g n a nci es  ......................................................................................................................... 4 0  
1 1. 6  Cli nic al L a b or at or y E v al u ati o ns  ........................................................................................... 4 0  


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1 1. 7  Ot h er S af et y M e as ur es  ....................................................................................................... 4 1  
1 1. 7. 1  E C G  ......................................................................................................................... 4 1  
1 1. 7. 2  Vit al Si g n s ............................................................................................................... 4 1  
1 1. 7. 3  P hysic al Ex a mi n ati o n  .............................................................................................. 4 2  
1 2  R e p orti n g C o nv e nti o ns  ................................................................................................................. 4 2  
1 3  T ec h nic al D et ails  ........................................................................................................................... 4 2  
1 4  S u m m ar y of C h a n g es fr o m t h e Pr ot oc ol  ....................................................................................... 4 2  
1 5  Bi bli o gr a p hy  .................................................................................................................................. 4 4  
1 6  A p p e n dix 1: List of T a bl es, Fi g ur es a n d Listi n gs  ............................................................................ 4 5  
1 6. 1  St u dy P o p ul ati o n  ................................................................................................................. 4 5  
1 6. 1. 1  T a bl es  ..................................................................................................................... 4 5  
1 6. 2  Effic ac y  ................................................................................................................................ 4 6  
1 6. 2. 1  T a bl es  ..................................................................................................................... 4 7  
1 6. 2. 2  Fi g ur es  .................................................................................................................... 5 0  
1 6. 3  S af et y  .................................................................................................................................. 5 5  
1 6. 3. 1  T a bl es  ..................................................................................................................... 5 5  
1 6. 4  D at a Listi n gs  ........................................................................................................................ 5 9  
1 7  A p p e n dix 2: Ecz e m a Ar e a a n d S e v erity I n d ex  ............................................................................... 6 3  
1 8  A p p e n dix 3: V ali d at e d I nv esti g at or Gl o b al Ass ess m e nt  ............................................................... 6 5  
1 9  A p p e n dix 4: S e v erity Sc ori n g of At o pic D er m atitis  ....................................................................... 6 6  
2 0  A p p e n dix 5: P ati e nt Ori e nt e d Ecz e m a M e as ur e  ........................................................................... 6 7  
2 1  A p p e n dix 6: D er m at ol o gy Q u alit y of Lif e I n d ex  ............................................................................ 6 8  
2 2  A p p e n dix 9: At o pic D er m atitis C o ntr ol T o ol  ................................................................................. 7 0  
2 3  A p p e n dix 1 0: M e d D R A I nt er n ati o n ally A gr e e d Or d er f or S yst e m Or g a n Cl ass  ............................ 7 2  
2 4  A p p e n dix 1 1: S af et y L a b or at or y Ev al u ati o ns  ................................................................................ 7 3  
 
 
 


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T a bl e of T a bl es  
T a bl e 1: I nt erc urr e nt E v e nt Str at e gi es of t h e Pri m ar y Esti m a n d  .......................................................... 2 9  
T a bl e 2: I nt erc urr e nt E v e nt Str at e gi es of t h e S ec o n d ary R es p o ns e E n d p oi nts  .................................... 3 1  
T a bl e 3: I nt erc urr e nt E v e nt Str at e gi es of C o nti n u o us Esti m a n d 1  ....................................................... 3 3  
T a bl e 4: I nt erc urr e nt E v e nt Str at e gi es f or R at e Esti m a n d 1  ................................................................. 3 4  
T a bl e 5: I nt erc urr e nt E v e nt Str at e gi es f or Ti m e t o E v e nt Esti m a n d 1  .................................................. 3 5  
T a bl e 6: I nt erc urr e nt E v e nt Str at e gi es f or C o nti n u o us Esti m a n d 3  ...................................................... 3 6  
T a bl e 7: I nt erc urr e nt E v e nt Str at e gi es of t h e 5 0 % r e d ucti o n of E A SI i n b o dy r e gi o ns  ......................... 3 7  
T a bl e 8: P CI Crit eri a f or Vit al Si g ns  ........................................................................................................ 4 1  
T a bl e 9: S u m m ar y of C h a n g es fr o m t h e Pr ot oc ol  ................................................................................. 4 3  
T a bl e 1 0: M e d D R A I nt er n ati o n ally A gr e e d S O C Or d er  ......................................................................... 7 2  
T a bl e 1 1: S af ety L a b or at ory P ar a m et ers a n d U nits  .............................................................................. 7 3  
 
T a bl e of Fi g ur es  
Fi g ur e 1: St u dy Sc h e m a  ......................................................................................................................... 1 1  
 
 


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2  
A b br e vi ati o ns a n d D efi niti o ns  
A D  
At o pic D er m atitis  
A D a M  
A n al ysis D at as et M o d el  
A D C T  
At o pic D er m atitis C o ntr ol T o ol  
A E  
A dv ers e E v e nt  
AL T  
Al a ni n e A mi n otr a nsf er as e  
A S T  
As p art at e A mi n otr a nsf er as e  
BL  
B as eli n e  
B P  
Bl o o d Pr ess ur e  
B S A  
B o dy S urf ac e Ar e a  
C R F  
C as e R e p ort f or m  
C R O  
C o ntr act R es e arc h Or g a niz ati o n  
C T C A E  
C o m m o n T er mi n ol o gy Crit eri a f or A dv ers e E v e nts  
DL QI  
D er m at ol o gy Lif e Q u alit y I n d ex  
d p  
D eci m al Pl ac e  
D P S  
D at a P oi nt S et  
E C G  
El ectr oc ar di o gr a m  
e C R F  
El ectr o nic C as e R e p ort F or m  
E A SI  
Ecz e m a Ar e a a n d S e v erity I n d ex  
E u dr a C T  
E ur o p e a n U ni o n Dr u g R e g ul ati n g A ut h oriti es Cli nic al Tri als  
F A S  
F ull A n al ysis S et  
F D A  
F o o d a n d Dr u g A d mi nistr ati o n  
G C P  
G o o d Cli nic al Pr actic e  
I C F 
I nf or m e d C o ns e nt F or m 
I C H 
I nt er n ati o n al C o u ncil f or H ar m o nis ati o n 
I g E 
I m m u n o gl o b uli n E 
I M P 
I nv esti g ati o n al M e dici n al Pr o d uct 
I R T 
I nt er activ e R es p o ns e T ec h n ol o gy 
J A K 
J a n us Ki n as e 
L S 
L e ast S q u ar es M e a n Esti m at e  
mL  
Millilitr e  
M e d D R A   
M e dic al Dicti o n ary f or R e g ul at or y Activiti es  
M M R M  
Mix e d M o d el f or R e p e at e d M e as ur es  
OL E  
O p e n -L a b el Ext e nsi o n 
P CI  
P ot e nti ally cli nic ally i m p ort a nt  
P D E  
P h os p h o di est er as e  
P O E M  
P ati e nt Ori e nt e d Ecz e m a M e as ur e  
P P -N R S  
P e a k Pr urit us N u m eric al R ati n g Sc al e  
P R O  
P ati e nt R e p ort e d O utc o m e  
P T  
Pr ef err e d T er m  
R N A  
Ri b o n ucl eic Aci d  
S A E  
S eri o us A dv ers e Ev e nt  


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 7  of 7 5  
S A P  
St atistic al A n alysis Pl a n  
S C O R A D  
S e v erit y Sc ori n g of At o pic D er m atitis  (S C O Ri n g At o pic D er m atitis ) 
S D -N R S  
Sl e e p Dist ur b a nc e N u m eric al R ati n g Sc al e  
S D T M  
S t a n d ar d D at a T a b ul ati o n M o d el  
S O C  
S yst e m Or g a n Cl ass  
T CI  
T o pic al C alci n e uri n I n hi bit ors  
T C S  
T o pic al C ortic ost er oi ds  
UL N  
U p p er Li mit of N or m al  
vI G A  
V ali d at e d I nv esti g at or Gl o b al Ass ess m e nt  
W H O D D  
W orl d H e alt h Or g a niz ati o n Dr u g Dicti o n ary  
 
 
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 8  of 7 5  
3  
I ntr o d ucti o n 
T h e p ur p os e of t his S A P is t o pr ovi d e all i nf or m ati o n t h at is n ec ess ary t o p erf or m t h e r e q uir e d 
st atistic al a n al ys es of st u dy E D P 1 8 1 5-2 0 8 . It als o d efi n es t h e s u m m ary T FLs t o b e i ncl u d e d i n t h e 
fi n al cli nic al st u dy r e p ort acc or di n g t o t h e pr ot oc ol. T h e S A P is b as e d u p o n, a n d ass u m es f a mili arit y, 
wit h t h e st u dy pr ot oc ol, v ersi o n 4 . 0, d at e d 1 6 -M A Y -2 0 2 2 . T his S A P o nl y c o v ers E D P 1 8 1 5 -2 0 7 st u dy 
as t h e p ossi bl e p ar e nt st u dy.  
 
C h a n g es fr o m  t h e a n alys es d escri b e d i n t h e pr ot oc ol ar e s u m m aris e d i n S ecti o n 1 4 . 
 
If a f ut ur e pr ot oc ol a m e n d m e nt n ec essit at es a s u bst a nti al c h a n g e t o t h e st atistic al a n al ysis of t h e 
st u dy d at a, t his S A P will b e a m e n d e d acc or di n gl y. T h e c o nt e nt of t his S A P is c o m p ati bl e w it h t h e I C H 
E 9 G ui d a nc e d oc u m e nt.  
 
4  
St u d y O bj ecti v es a n d E n d p oi nts  
4. 1  
St u d y O bj ecti v es  
T h e pri m ar y o bj ecti v e of t h e st u dy is : 
•  
T o ev al u at e t h e l o n g -t er m s af et y a n d t ol er a bility of E D P 1 8 1 5 i n t h e tr e at m e nt of at o pic 
d er m atitis  
 
T h e s ec o n d ary o bj ectiv e of t h e st u dy is: 
•  
T o ev al u at e t h e effic ac y of l o n g -t er m tr e at m e nt wit h E D P 1 8 1 5 i n t h e tr e at m e nt of at o pic 
d er m atitis  
 
T h e ex pl or at ory o bj ectiv es of t h e st u dy ar e:  
•  
T o ev al u at e t h e ti m e t o o ns et of cli nic al r es p o ns e t o E D P 1 8 1 5  
•  
T o ev al u at e ot h er as p ects of t h e effic ac y of E D P 1 8 1 5 as a tr e at m e nt f or at o pic d er m atitis  
•  
T o ev al u at e t h e r el ati o ns hi p of E D P 1 8 1 5 tr e at m e nt wit h bi o m ar k ers s uc h as i m m u n e pr ot ei n 
m ar k ers a n d i m m u n e c ell R N A pr ofil e i n bl o o d  
 
4. 2  
E n d p oi nts  
T h e pri m ar y e n d p oi nt s f or t h e st u dy ar e: 
•  
T h e i nci d e nc e a n d r at e p er 1 0 0 p ati e nt -y e ars of tr e at m e nt -e m er g e nt a dv ers e e v e nts d uri n g 
t h e 3 6-w e e k tr e at m e nt a n d 4 -w e e k f oll o w -u p p eri o d  
•  
T h e i nci d e nc e a n d r at e p er 1 0 0 p ati e nt -y e ars of tr e at m e nt -e m er g e nt a dv ers e e v e nts d uri n g 
t h e tr e at m e nt p eri o d of t his st u dy a n d t h e r el ev a nt p ar e nt st u dy 
 
T h e  s ec o n d ary effic ac y e n d p oi nts f or t h e st u dy will b e e v al u at e d at all sc h e d ul e d visits  ( u nl ess 
ot h er wis e  s p ecifi e d), wit h m e as ur es i nv olvi n g c h a n g es fr o m b as eli n e  usi n g t h e b as eli n e ass ess m e nt 
fr o m t h e r el ev a nt E D P 1 8 1 5 p ar e nt st u dy. T h e s ec o n d ar y e n d p oi nts ar e as f oll o ws: 
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g Ecz e m a Ar e a a n d S e v erit y I n d ex  ( E A SI)-5 0  
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g E A SI-7 5  


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 9  of 7 5  
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g E A SI-9 0  
•  
M e a n a bs ol ut e c h a n g e a n d p erc e nt a g e c h a n g e fr o m b as eli n e i n E A SI Sc or e  
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g V ali d at e d I nv esti g at or's Gl o b al Ass ess m e nt ( vI G A) of 0 
or 1 wit h a ≥2 -p oi nt im p r ov e m e nt fr o m b as eli n e 
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g vI G A of 0 or 1 
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g vI G A of 0 
•  
M e a n a bs ol ut e c h a n g e a n d p erc e nt a g e c h a n g e fr o m b as eli n e i n vI G A * B S A  ( B S A = b o dy 
s urf ac e ar e a) 
•  
M e a n a bs ol ut e c h a n g e a n d p erc e nt a g e c h a n g e fr o m b as eli n e i n B S A  
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g B S A -5 0  
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g B S A -7 5  
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g B S A r e d ucti o n t o 3 % B S A or l ess  
•  
M e a n a bs ol ut e c h a n g e a n d p erc e nt a g e c h a n g e fr o m b as eli n e i n S C O Ri n g At o pic D er m atitis 
( S C O R A D) sc or e 
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g S C O R A D -3 5  
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g S C O R A D -5 0  
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g S C O R A D -7 5  
•  
M e a n a bs ol ut e c h a n g e a n d p erc e nt a g e c h a n g e fr o m b as eli n e i n D er m at ol o gy Li f e Q u alit y 
I n d ex (DL QI ) sc or e 
•  
P erc e nt a g e of P artici p a nts ac hi e vi n g a r e d ucti o n of ≥4 i n t h e DL QI  sc or e, of t h os e wit h a 
sc or e of ≥4 at b as eli n e  
•  
M e a n a bs ol ut e c h a n g e fr o m b as eli n e i n  P e a k Pr urit us N u m eric al R ati n g Sc al e  (P P -N R S ) sc or e 
•  
P erc e nt a g e of p artici p a nts ac hi e vi n g a r e d ucti o n of ≥2 i n t h e P P -N R S, of t h os e wit h a sc or e of 
≥2 at b as eli n e  
•  
P erc e nt a g e of p artici p a nts ac hi e vi n g a r e d ucti o n of ≥4 i n t h e P P -N R S, of t h os e wit h a sc or e of 
≥4 at b as eli n e  
•  
M e a n a bs ol ut e c h a n g e fr o m b as eli n e i n Sl e e p Dist ur b a nc e R ati n g Sc al e ( S D -N R S ) sc or e 
•  
P erc e nt a g e of p artici p a nts a c hi e vi n g a r e d ucti o n of ≥2 i n S D -N R S sc or e, of t h os e wit h a  sc or e 
of ≥2 at b as eli n e  
•  
M e a n a bs ol ut e c h a n g e a n d p erc e nt a g e c h a n g e fr o m b as eli n e i n P ati e nt Ori e nt e d Ecz e m a 
M e as ur e ( P O E M)  sc or e 
•  
P erc e nt a g e of p artici p a nts ac hi e vi n g a r e d ucti o n of ≥4 i n t h e P O E M sc or e, of t h os e wit h a 
sc or e of ≥4 at b as eli n e  
•  
N u m b er of c o urs es p er p ati e nt -y e ar of a n y r esc u e m e dic ati o n ( n ot i ncl u di n g a nti b act eri al 
t h er a py) 
•  
N u m b er of c o urs es p er p ati e nt -y e ar of t o pic al c ortic ost er oi ds of a n y p ot e ncy  
•  
N u m b er of c o urs es p er p ati e nt -y e ar of t o pic al t acr oli m us ( 0. 1 %), t o pic al pi m ecr oli m us ( 1 %) 
or g r a d e VII t o pic al c ortic ost er oi d 
•  
N u m b er of c o urs es p er p ati e nt -y e ar of m o d er at e p ot e nc y ( g r a d e I V a n d V) t o pic al st er oi ds 
 
T h e s ec o n d ary s af et y e n d p oi nts f or t h e st u dy ar e:  
•  
A dv ers e ev e nts a n d s eri o us a d v ers e ev e nts  


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 1 0  of 7 5  
•  
C h a n g e fr o m b as eli n e i n vit al si g ns  
•  
C h a n g e fr o m b as eli n e i n E C G p ar a m et ers  
•  
C h a n g e fr o m b as eli n e i n cli nic al l a b or at ory p ar a m et ers  
•  
C h a n g e fr o m b as eli n e i n p hysic al ex a mi n ati o n fi n di n gs  
•  
W orst -c as e c h a n g e fr o m b as eli n e wit h r es p ect t o p ot e nti all y cli nic al i m p ort a nt crit eri a f or 
vit al si g ns, Q Tc F a n d cli nic al l a b or at or y p ar a m et ers  
•  
W orst -c as e c h a n g e fr o m b as eli n e wit h r es p ect t o v al u es o utsi d e t h e n or m al r a n g es f or 
cli nic al l a b or at ory p ar a m et ers 
 
Ex pl or at ory e n d p oi nts t o ev al u at e t h e ti m e t o o ns et of cli nic al r es p o ns e ar e:  
•  
Ti m e t o first ac hi ev e m e nt of E A SI -5 0  
•  
Ti m e t o first ac hi ev e m e nt of s ust ai n e d E A SI -5 0  
 
Ot h er  ex pl or at ory e n d p oi nts will us e d t o  ev al u at e ot h er as p ects of t h e effic ac y of E D P 1 8 1 5 as a 
tr e at m e nt f or at o pic d er m atitis a n d ar e:  
•  
C h a n g es fr o m b as eli n e i n At o pic D er m atitis C o ntr ol T o ol  ( A D C T) sc or es 
•  
M e a n a bs ol ut e a n d p erc e nt a g e c h a n g e i n t h e f o ur  b o dy r e gi o n sc or es of t h e E A SI  
•  
P erc e nt a g e  of p artici p a nts ac hi e vi n g at l e ast a 5 0 % r e d ucti o n i n e ac h of t h e f o ur b o dy r e gi o n 
sc or es of t h os e wit h a n o n-z er o sc or e f or t h e r el ev a nt r e gi o n at b as eli n e 
•  
P erc e nt a g e of p artici p a nts w h o c h a n g e r es p o ns e st at es fr o m D a y -1 t o W e e ks 8, 1 6, 2 4 a n d 
3 6. R es p o ns e st at es will b e d efi n e d usi n g t h e E A SI sc or e p erc e nt a g e c h a n g e fr o m b as eli n e  
wit h c at e g ori es f or > = 2 5 % i ncr e as e, n o c h a n g e ( < 2 5 % i ncr e as e t o < 2 5 % d ecr e as e), 2 5 % t o 
< 5 0 % d ecr e as e, 5 0 % t o < 7 5 % d ecr e as e, 7 5 % d ecr e as e t o  < 9 0 % d ecr e as e, > = 9 0 % d ecr e as e  
•  
D ail y m e a n a bs ol ut e c h a n g e fr o m b as el i n e i n P P-N R S a n d S D -N R S sc or es  
 
T h e f oll o wi n g e n d p oi nts will b e us e d t o e v al u at e t h e r el ati o ns hi p of E D P 1 8 1 5 tr e at m e nt wit h 
bi o m ark ers s uc h as i m m u n e pr ot ei n m ar k ers a n d i m m u n e c ell R N A pr ofil e i n bl o o d . N ot e t h at 
a n al ys es  of t h es e bi o m ar k ers ex pl or at or y e n d p oi nts will b e a d dr ess e d i n a s e p ar at e a n al ysis pl a n a n d 
will n ot b e f urt h er disc uss e d i n t his  d oc u m e nt : 
•  
C h a n g es fr o m b as eli n e i n s er u m i m m u n e pr ot ei n m ark ers i ncl u di n g I m m u n o gl o b uli n E (I g E) 
•  
C h a n g es fr o m b as eli n e i n i m m u n e c ell R N A pr ofil e  
  
5  
St u d y M et h o ds  
5. 1  
G e n er al St u d y D esi g n a n d Pl a n  
T his is a n O p e n -L a b el Ext e nsi o n ( OL E), m ultic e ntr e st u dy t o ev al u at e t h e l o n g-t er m s af et y, 
t ol er a bility a n d effic acy of  E D P 1 8 1 5 i n p artici p a nts wit h mil d, m o d er at e a n d s e v er e  at o pic 
d er m atitis.  P artici p a nts w h o h a v e c o m pl et e d t h e 1 6 -w e e k tr e at m e nt p eri o d i n t h e E D P 1 8 1 5 -2 0 7 
p ar e nt st u dy m ay b e eli gi bl e t o e nr ol  i n t his st u dy. 
 
T h e d os es a d mi nist er e d i n t his st u dy ar e t h e s a m e as t h os e a d mi nist er e d i n t h e E D P 1 8 1 5 -2 0 7 p ar e nt 
st u dy a n d ar e as f oll o ws: 
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 1 1  of 7 5  
•  
Gr o u p 1: 1. 6x 1 0 1 1 t ot al c ells of E D P 1 8 1 5 a d mi nist er e d as 2 c a ps ul es o nc e d ail y 
•  
Gr o u p 2: 6. 4x 1 0 1 1 t ot al c ells of E D P 1 8 1 5 a d mi nist er e d as 2 c a ps ul es o nc e d ail y  
•  
Gr o u p 3: 8. 0x 1 0 1 0 tot al c ells of E D P 1 8 1 5 a d mi nist er e d as 1 c a ps ul e o nc e d aily  
 
N o pl ac e b o will b e a d mi nist er e d i n t his st u dy. T h e f oll o wi n g will a p pl y f or all E D P 1 8 1 5 -2 0 7 p artici p a nts 
w h o tr a nsiti o n i nt o t his st u dy:   
 
•  
E D P 1 8 1 5 -2 0 7 C o h ort 1 p artici p a nts will r ec eiv e 1. 6x 1 0 1 1 t ot al c ells of E D P 1 8 1 5 i n E D P 1 8 1 5-
2 0 8 ( Gr o u p 1)  
•  
E D P 1 8 1 5 -2 0 7 C o h ort 2 p artici p a nts will r ec eiv e 6. 4x 1 0 1 1 t ot al c ells of E D P 1 8 1 5 i n E D P 1 8 1 5-
2 0 8 ( Gr o u p 2)  
•  
E D P 1 8 1 5 -2 0 7 C o h ort 3 p artici p a nts will b e r a n d o miz e d 1: 1 t o r ec ei v e eit h er 1. 6x 1 0 1 1 t ot al c ells 
of E D P 1 8 1 5 ( Gr o u p 1), or 6. 4x 1 0 1 1 t ot al c ells of E D P 1 8 1 5 ( Gr o u p 2) i n E D P 1 8 1 5-2 0 8  
•  
E D P 1 8 1 5 -2 0 7 C o h ort 4 p artici p a nts will r ec eiv e 8. 0x 1 0 1 0 t ot al c ells of E D P 1 8 1 5 i n E D P 1 8 1 5-
2 0 8 ( Gr o u p 3)  
 
T h e t ot al n u m b er of p artici p a nts will b e d e p e n d e nt o n t h e n u m b er of  p artici p a nts w h o el ect a n d ar e 
eli gi bl e t o p artici p at e i n t h e OL E  st u dy f oll o wi n g p artici p ati o n i n t h e E D P 1 8 1 5-2 0 7 p ar e nt st u dy.  
 
T h e t ot al d ur ati o n of p artici p ati o n i n t his st u dy is u p t o a m axi m u m of 4 0 w e e ks fr o m D ay -1 t o 
f oll o w-u p.  As s h o w n i n Fi g ur e 1 , p artici p a nts will u n d er g o a D ay -1 visit, a 3 6 -w e e k tr e at m e nt p eri o d 
c o nsisti n g of 6 st u dy visits a n d a 4 -w e e k p ost -tr e at m e nt f oll o w-u p visit.  
 
Fi g ur e 1 : St u d y Sc h e m a   
5. 2  
R a n d o mis ati o n a n d Bli n di n g  
T his is a n OL E  st u dy wit h all p artici p a nts t a ki n g E D P 1 8 1 5 c a ps ul es a n d as s uc h n o bli n di n g is r e q uir e d 
f or t h e st u dy m e dic ati o n i n t his st u dy. P artici p a nts i n C o h ort 3 i n t h e E D P 1 8 1 5 -2 0 7 p ar e nt st u dy t h at 
ar e eli gi bl e f or t his st u dy will b e r a n d o mi ze d 1: 1 t o r ec ei v e eit h er 1. 6x 1 0 1 1 t ot al c ells of E D P 1 8 1 5, or 
6. 4x 1 0 1 1 t ot al c ells of E D P 1 8 1 5. 
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 1 2  of 7 5  
I nv esti g at ors a n d p artici p a nts will c o nti n u e t o b e bli n d e d t o t h e p artici p a nt’s tr e at m e nt assi g n m e nt 
i n t h e E D P 1 8 1 5-2 0 7 p ar e nt st u dy t o mi ni miz e bi as.  
5. 3  
D eri v e d v ari a bl es  
5. 3. 1  
G e n er al  
5. 3. 1. 1  R el at i v e D a y  
T h e r el ativ e d a y of a n ass ess m e nt si nc e t h e st art of 2 0 8 st u dy will b e c alc ul at e d as:  
•  
F or m e as ur e m e nt p erf or m e d o n or aft er t h e d at e of first d os e  i n t his st u dy:  
D at e of ass ess m e nt –  d at e of st art of tr e at m e nt +  1  
 
•  
F or m e as ur e m e nts p erf or m e d b ef or e t h e d at e of first d os e  i n t his st u dy: 
D at e of ass ess m e nt –  d at e of st art of tr e at m e nt 
 
T h e r el ativ e d a y of a n ass ess m e nt si nc e t h e first d os e of acti v e I M P (i n t his or p ar e nt st u dy) will b e 
c alc ul at e d as: 
•  
F or m e as ur e m e nt p erf or m e d o n or aft er t h e first d os e of activ e I M P:  
D at e of ass ess m e nt –  d at e of t h e first d os e of activ e I M P +  1  
 
•  
F or m e as ur e m e nts p erf or m e d b ef or e t h e first d os e of acti v e I M P: 
D at e of ass ess m e nt –  d at e of t h e first d os e of activ e I M P 
 
5. 3. 1. 2  B as eli n e  
T h e l ast n o n -missi n g v al u e c oll ect e d b ef or e first st u dy d os e  i n t h e p ar e nt st u dy will b e t a k e n as t h e 
b as eli n e m e as ur e m e nt f or all p ar a m et ers. If d at a is c oll ect e d o n D a y 1 of t h e p ar e nt st u dy it will b e 
ass u m e d t o b e pr e -d os e  r e g ar dl ess of a n associ at e d ti m e .  
 
5. 3. 1. 3  C h a n g e a n d P erc e nt a g e C h a n g e fr o m B as eli n e  
C h a n g e fr o m b as eli n e will b e c alc ul at e d as:  
C h a n g e  fr o m b as eli n e = v al u e at ti m e p oi nt –  b as eli n e v al u e  
C h a n g e fr o m b as eli n e will b e pr es e nt e d t o t h e s a m e l e v el of pr ecisi o n as t h e ori gi n al v al u e i n t h e 
listi n gs. 
 
P erc e nt a g e c h a n g e fr o m b as eli n e will b e c alc ul at e d as:  
  
P erc e nt a g e  c h a n g e fr o m b as eli n e = 1 0 0 *(c h a n g e fr o m b as eli n e / b as eli n e v al u e)  
P erc e nt a g e c h a n g e fr o m b as eli n e will b e pr es e nt e d t o 1 d eci m al pl ac e ( d p) i n t h e listi n gs.  
 
5. 3. 2  
D e m o gr a p hic a n d B ac k gr o u n d D at a  
H ei g ht m ay b e r ec or d e d i n c m or i nc h es. H ei g ht i n i nc h es will b e c o nv ert e d t o h ei g ht i n c m as 
f oll o ws: 
  
H ei g ht (c m) = H ei g ht (i nc h es) * 0. 3 9 3 7  
H ei g ht (c m) will b e pr es e nt e d t o 1 d p i n t h e listi n gs.  
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 1 3  of 7 5  
W ei g ht m a y b e r ec or d e d i n k g or p o u n ds.  W ei g ht i n p o u n ds will b e c o nv ert e d t o w ei g ht i n k g as 
f oll o ws: 
  
W ei g ht (k g) = W ei g ht ( p o u n ds) * 0. 4 5 3 6  
W ei g ht (k g) will b e pr es e nt e d t o 1 d p i n t h e listi n gs.  
 
B o dy m ass i n d ex ( B MI) will b e c alc ul at e d as:  
B MI ( k g/ m 2) = W ei g ht (k g) / [ h ei g ht (c m)/ 1 0 0]2  
B MI ( k g/ m 2) will b e pr es e nt e d t o 1 d p i n t h e listi n gs. 
 
5. 3. 2. 1  St u d y Dr u g  C o m pli a nc e  
P artici p a nts i n gr o u ps  1  a n d 2  will b e ex p ect e d t o d os e o nc e d aily wit h 2 c a ps ul es p er d os e  (2 
c a ps ul es p er d ay) ; i n gr o u p  3 –  o nc e d aily wit h 1 c a ps ul e . 
 
C o m pli a nc e will b e c alc ul at e d acr oss t h e w h ol e tr e at m e nt p eri o d  i n t his st u dy. 
 
Ex p ect e d c a ps ul es f or t h e tr e at m e nt p eri o d f or gr o u ps 1 a n d 2 will b e c alc ul at e d as:  
Ex p ect e d c a ps ul es = 2 *( E n d d at e of tr e at m e nt p eri o d  –  St art d at e of tr e at m e nt p eri o d  + 1 ). 
 
Ex p ect e d c a ps ul es f or t h e tr e at m e nt p eri o d f or gr o u p 3 will b e c alc ul at e d as:  
Ex p ect e d c a ps ul es = E n d d at e of tr e at m e nt p eri o d  –  St art d at e of tr e at m e nt p eri o d  + 1 . 
 
E n d d at e of tr e at m e nt p eri o d = D at e of t h e l ast d os e of st u dy dr u g . 
St art d at e of tr e at m e nt p eri o d = D ay 1.  
 
Act u al c a ps ul es t a k e n will b e c alc ul at e d fr o m t h e d osi n g l o g usi n g e ntri es b et w e e n t h e st art a n d e n d 
d a ys i ncl usiv el y.  
 
St u dy dr u g c o m pli a nc e will b e c alc ul at e d as: 
  
St u dy dr u g c o m pli a nc e ( %) = 1 0 0 * Act u al c a ps ul es t a k e n/ Ex p ect e d c a ps ul es t ak e n.  
 
St u dy dr u g co m pli a nc e will als o b e c at e g oriz e d as:  
•  
< 8 0 %  
•  
≥8 0 %  
 
5. 3. 2. 2  E m olli e nt C o m pli a nc e  
All p artici p a nts m ust us e a n e m olli e nt t wic e d aily  u ntil t h e W e ek 4 0 F oll o w -u p Visit.  
 
C o m pli a nc e will b e c alc ul at e d acr oss t h e w h ol e tr e at m e nt p eri o d  a n d f oll o w -u p p eri o d  i n t his st u dy. 
 
Ex p ect e d n u m b er of a p plic ati o ns  f or t h e tr e at m e nt + f oll o w -u p  p eri o d will b e c alc ul at e d as:  
Ex p ect e d n u m b er of a p plic ati o ns  = 2 *( E n d d at e of p eri o d  –  St art d at e of p eri o d + 1).  
E n d d at e of p eri o d = E n d of st u dy d ay . St art d at e of p eri o d  = D ay 1.  




St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 1 5  of 7 5  
5. 3. 3  
Effic ac y  
5. 3. 3. 1  Ecz e m a Ar e a a n d S e v erit y I n d e x  ( E A SI) 
T h e Ecz e m a Ar e a a n d S e v erit y I n d ex ( E A SI)  will b e c alc ul at e d wit hi n t h e  
 s yst e m a n d t a k e n 
dir ectl y fr o m t h e s u p pli e d d at a.   E A SI sc or e r a n g es fr o m 0 t o 7 2  a n d c o m bi n es t h e i n di vi d u al sc or es 
fr o m th e f o ur i n divi d u al b o dy r e gi o ns of h e a d a n d n eck, u p p er li m bs, tr u n k, l o w er li m bs . H e a d a n d 
n ec k b o dy r e gi o n sc or e r a n g es fr o m 0 t o 7. 2, u p p er li m bs –  fr o m 0 t o 1 4. 4, tr u nk –  fr o m 0 t o 2 1. 6, 
l o w er li m bs –  fr o m 0 t o 2 8. 8. F urt h er i nf or m ati o n o n t h e sc ori n g of t h e E A SI is pr o vi d e d i n S ecti o n 
1 7 . 
E A SI -5 0, E A SI -7 5  a n d  E A SI -9 0 r es p o ns es ar e d efi n e d r es p ectiv ely b y  at l e ast  a 5 0 %, 7 5 %  a n d  9 0 % 
d ecr e as e  fr o m B as eli n e i n t h e E A SI  sc or e. 
 
S ust ai n e d E A SI -5 0 r es p o ns e is d efi n e d as o n e w hic h is pr es e nt at c o ns ec uti v e visits s p a n ni n g at l e ast 
8 w e e ks i n t h e a bs e nc e of r esc u e m e dic ati o n . T h e s ust ai n e d r es p o ns e is c o nsi d er e d t o h a v e b e e n 
first ac hi ev e d at t h e first of t h e c o ns ec uti v e visits.  
 
5. 3. 3. 2  T h e P erc e nt of B o d y S urf ac e A r e a I n v ol v e m e nt ( B S A) 
T h e B o dy S urf ac e Ar e a (B S A ) will b e c alc ul at e d as p art of E A SI sc or e i n t h e  
 s yst e m a n d 
t a k e n dir ectl y fr o m t h e s u p pli e d d at a.  T h e p erc e nt of B S A i nv olv e m e nt will b e esti m at e d f or e ac h 
p artici p a nt, w h er e 1 % is  a p pr oxi m at e ly t h e ar e a of t h e p artici p a nt’s h a n d pri nt. 
 
B S A -5 0 a n d B S A -7 5  r es p o ns es ar e  d efi n e d r es p ecti v ely b y  at l e ast  a 5 0 % a n d 7 5 %  r e d ucti o n fr o m 
B as eli n e i n t h e B S A .  
 
5. 3. 3. 3  V ali d at e d I n v esti g at or’s Gl o b al Ass ess m e nt  ( vI G A) 
T h e V ali d at e d I nv esti g at or Gl o b al Ass ess m e nt sc al e f or At o pic D er m atitis ( vI G A)  will b e c alc ul at e d 
wit hi n t h e  
 syst e m a n d t ak e n dir ectl y fr o m t h e s u p pli e d d at a.  T h er e is a  st a n d ar dize d 
gr a di n g s yst e m b as e d o n a n o v er all ass ess m e nt of t h e d e gr e e of er yt h e m a,  p a p ul ati o n/i n d ur ati o n, 
lic h e nific ati o n, a n d o ozi n g/cr usti n g. I n i n d et er mi n at e c as es, ext e nt will b e us e d t o diff er e nti at e 
b et w e e n sc or es –  b ut ot h er wis e ext e nt is n ot us e d i n t h e sc ori n g s yst e m. T h e  vI G A sc or e r a n g es fr o m 
0  ( Cl e ar s ki n) t o 4 ( S ev er e dis e as e).  
 
5. 3. 3. 4  S C O Ri n g At o pi c D er m atitis ( S C O R A D) 
T h e S C O Ri n g At o pic D er m atitis ( S C O R A D)  will b e c alc ul at e d wit hi n t h e  
 s yst e m a n d t a k e n 
dir ectl y fr o m t h e s u p pli e d d at a.  T h er e is a n i n v esti g at or -r at e d ar e a sc or e w hic h us es t h e r ul e of 
ni n es t o ass ess dis e as e ext e nt, a n d a dis e as e i nt e nsity sc or e c o m prisi n g  eryt h e m a, s w elli n g, 
o ozi n g/cr usti n g, exc ori ati o n, lic h e nific ati o n, a n d dr y n ess. A d diti o n ally, t h er e  is a s u bj ecti v e 
s y m pt o ms c o m p o n e nt w hic h c o nsi d ers itc h a n d sl e e pl ess n ess sc or e d usi n g a vis u al  a n al o g u e sc al e. 
T h es e sc or es c o m bi n e t o giv e a S C O R A D sc or e b et w e e n 0 a n d  1 0 3 .  
 
S C O R A D -3 5, S C O R A D -5 0 a n d S C O R A D -7 5  r es p o ns es ar e  d efi n e d r es p ecti v ely by  at l e ast  a 3 5 %, 5 0 % 
a n d 7 5 %  r e d ucti o n fr o m B as eli n e i n t h e S C O R A D  sc or e.  
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 1 6  of 7 5  
5. 3. 3. 5  P ati e nt Ori e nt e d Ecz e m a M e as ur e  ( P O E M) 
T h e P ati e nt Ori e nt e d Ecz e m a M e as ur e ( P O E M)  will b e c alc ul at e d wit hi n t h e 
 a n d 
t a k e n dir ectl y fr o m t h e s u p pli e d d at a.  It i ncl u d es a s eri es of 7 q u esti o ns, m e as uri n g itc h, sl e e p, 
bl e e di n g,  w e e pi n g/ o ozi n g, cr ac ki n g, fl a ki n g, a n d dr y n ess/r o u g h n ess o v er t h e l ast w e ek, a n d is sc or e d 
by t h e  p artici p a nt. E ac h of t h e 7 q u esti o ns is sc or e d fr o m 0 ( n o d ays) t o 4 ( ev ery d a y), givi n g a P O E M  
sc or e r a n g e fr o m 0 t o 2 8, wit h hi g h er sc or es r e pr es e nti n g hi g h er dis e as e s ev erity . 
 
P O E M r es p o ns e is d e fi n e d as a r e d ucti o n of ≥4  i n t h e P O E M sc or e if a p artici p a nt h as  a sc or e of ≥4  at 
b as eli n e . 
 
5. 3. 3. 6  D er m at ol o g y Lif e Q u alit y I n d e x  ( DL QI) 
T h e DL QI is a 1 0 -it e m q u esti o n n air e wit h e ac h it e m sc or e d fr o m 0 t o 3.   
 
T h e DL QI sc or e is t h e s u m of t h e 1 0 i n di vi d u al it e ms  a n d r a n g es fr o m 0 t o 3 0, wit h hi g h er sc or es 
i n dic ati n g gr e at er i m p air m e nt of q u alit y of lif e.  F urt h er i nf or m ati o n o n t h e sc ori n g of t h e DL QI is 
pr o vi d e d i n S ecti o n 2 1 . 
 
DL QI r es p o ns e is d efi n e d as a r e d ucti o n of ≥4 i n t h e DL QI  sc or e if a p artici p a nt h as a sc or e of ≥4 at 
b as eli n e  (a 4 -p oi nt c h a n g e fr o m b as eli n e is c o nsi d er e d t h e mi ni m al cli nic all y i m p ort a nt diff er e nc e 
t hr es h ol d). 
 
5. 3. 3. 7  P e a k Pr urit us N u m eric al R ati n g Sc al e  ( P P-N R S)  
T h e P e a k Pr urit us N u m eric al R ati n g Sc al e ( P P -N R S)  is a sc al e fr o m 0 t o 1 0 f or p artici p a nts t o r at e 
t h eir w orst itc h t h at t h e y h a v e ex p eri e nc e d o v er t h e pr e vi o us 2 4 h o urs. T h e P P -N R S will  b e 
c o m pl et e d d aily vi a a d ail y q u esti o n n air e fr o m t h e D ay -1 visit t o t h e w e e k 4 0 visit.  
 
P P -N R S sc or e at e ac h visit is c alc ul at e d as t h e m e a n itc h d aily sc or e f or t h e 7 d ays pri or t o a n d 
i ncl u di n g t h e visit d at e. At l e ast 4 d ail y sc or es m ust b e a v ail a bl e f or t h e sc or e at t h e r el ev a nt visit t o 
b e c o nsi d er e d ev al u a bl e.  
 
P P -N R S r es p o ns es ar e d efi n e d as a r e d ucti o n of ≥2 a n d ≥4  i n t h e P P -N R S sc or e if a p artici p a nt h as  a 
sc or e of ≥2 a n d ≥4, r es p ecti v el y,  at b as eli n e  (a ≥2 -4 -p oi nt c h a n g e fr o m b as eli n e is c o nsi d er e d t h e 
mi ni m al cli nic all y i m p ort a nt diff er e nc e t hr es h ol d ). 
 
5. 3. 3. 8  Sl e e p Dist ur b a nc e N u m eric al R ati n g Sc al e  ( S D-N R S)  
T h e Sl e e p Dist ur b a nc e N u m eric al R ati n g Sc al e ( S D -N R S) is a sc al e fr o m 0 t o 1 0 f or p artici p a nts t o r at e 
t h eir w orst sl e e p t h at t h e y h a v e exp eri e nc e d  o v er t h e pr e vi o us 2 4 h o urs . T h e S D -N R S will b e 
c o m pl et e d d aily vi a a d ail y q u esti o n n air e fr o m t h e D ay -1 visit t o t h e w e e k 4 0 visit . 
 
S D -N R S sc or e at e ac h visit is c alc ul at e d as t h e m e a n  sl e e p d aily sc or e f or t h e 7 d ays pri or t o a n d 
i ncl u di n g t h e visit d at e. At l e ast 4 d ail y sc or es m ust b e a v ail a bl e f or t h e sc or e at t h e r el ev a nt visit t o 
b e c o nsi d er e d ev al u a bl e.  


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 1 7  of 7 5  
 
S D -N R S r es p o ns e is d efi n e d as a r e d ucti o n of ≥2  i n t h e S D -N R S sc or e if a p artici p a nt h as  a sc or e of ≥2  
at b as eli n e  (a 2 -p oi nt c h a n g e fr o m b as eli n e is c o nsi d er e d t h e mi ni m al cli nic ally i m p ort a nt diff er e nc e 
t hr es h ol d). 
 
5. 3. 3. 9  At o pic D er m atitis C o ntr ol T o ol  ( A D C T) 
T h e At o pic D er m atitis C o ntr ol T o ol ( A D C T) is a 6 -q u esti o n P R O i nstr u m e nt us e d t o d et ect c h a n g e  of 
dis e as e activit y i n a p ers o n o v er ti m e. T h er e ar e six m ai n ar e as t h at ass ess t h e m ulti -di m e nsi o n al  
as p ects of dis e as e c o ntr ol o v er t h e c o urs e of a w e e k, sc or e d b et w e e n 0 -4 . A D C T sc or es r a n g e fr o m a 
mi ni m u m sc or e  of 0 a n d a m axi m u m sc or e of  2 4. A hi g h er sc or e i n dic at es l o w er A D c o ntr ol.  
 
5. 3. 3. 1 0  R esc u e T h er a p y  
R esc u e t h er a py us e is all o w e d t hr o u g h o ut t h e e ntir e st u dy : s el ect e d t o pic al c ortic ost er oi ds a n d 
calci n e uri n in hi bit ors , s yst e mic a nti micr o bi als a n d t o pic al a nti b act eri al m a y b e pr escri b e d. A n 
u nsc h e d ul e d visit will b e p erf or m e d t o c oll ect t h e ass ess m e nts pri or t o a d mi nist eri n g a n y r esc u e 
t h er a py, if n e e d e d.  
R esc u e t h er a py us e  will b e d oc u m e nt e d  as c o nc o mit a nt m e dic ati o n o nc e pr escri b e d a n d i n a  d aily  
s y m pt o m di ary d uri n g t h e w h ol e c o urs e. E ac h  r esc u e t h er a py c o urs e will b e r ec or d e d i n c o nc o mit a nt 
m e dic ati o n C R F s e p ar at ely, r es ulti n g i n a o n e r ec or d i n a c o nc o mit a nt m e dic ati o n d at as et f or e ac h 
c o urs e.  
A ny m e dic ati o ns t ak e n d uri n g t h e st u dy a n d cl assifi e d as T S C/ T CI r esc u e t h er a py m e dic ati o ns i n  t h e 
s p o ns or pr ovi d e d s pr e a ds h e et will b e c o nsi d er e d as r esc u e t h er a py wit h exc e pti o n f or m e dic ati o ns 
w hic h st o p p e d at l e ast 1 4 d a ys b ef or e D ay 1.  
T h e n u m b er of c o urs es of T C S/ T CI r esc u e t h er a py  will b e e v al u at e d  f or t w o p eri o ds: t h e p eri o d 
b e gi n ni n g  wit h t h e first d os e of activ e I M P i n t his st u dy a n d  t h e p eri o d b e gi n ni n g wit h t h e first d os e 
of activ e  I M P acr oss t his st u dy a n d t h e p ar e nt st u dy u p t o t h e e n d of tr e at m e nt . R esc u e t h er a py 
c o urs e will o nl y b e c o u nt e d at t h e st art d a y of c o urs e. If t h e r esc u e t h er a py c o urs e st arts i n o n e 
p eri o d a n d c o nti n u es t o t h e n ext p eri o d it will b e c o u nt e d o nly i n t h e first p eri o d w h er e t h e st art of 
t h e c o urs e b el o n gs.  
 
5. 3. 4  
S af et y  
5. 3. 4. 1  D ur ati o n of E x p os ur e  
T h e d ur ati o n of ex p os ur e i n t his st u dy will b e c alc ul at e d as  
  
D ur ati o n of ex p os ur e ( d a ys) = Tr e at m e nt st o p d at e  i n 2 0 8 –  T r e at m e nt st art d at e i n 2 0 8 + 1  
 
T h e d ur ati o n of activ e ex p os ur e i n t his a n d p ar e nt st u dy will b e c alc ul at e d as  
  
D ur ati o n of ex p os ur e ( d a ys) = T r e at m e nt st o p d at e i n 20 8  –  Activ e t r e at m e nt st art d at e*  + 1  
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 1 8  of 7 5  
*If p ati e nt r ec ei v e d activ e tr e at m e nt i n p ar e nt st u dy, t h e n c o nsi d er t h e st art d at e of activ e 
tr e at m e nt fr o m p ar e nt st u dy, ot h er wis e, st art of tr e at m e nt i n 2 0 8. 
 
5. 3. 4. 2  Tr e at m e nt -E m er g e nt A d v ers e E v e nts  
A n a dv ers e ev e nt ( A E) will b e cl assifi e d as ‘tr e at m e nt-e m er g e nt’ if t h e o ns et d at e/ti m e w as aft er t h e 
st art d at e/ti m e of st u dy tr e at m e nt a n d o n or b ef or e 3 0  d a ys aft er l ast d os e of st u dy tr e at m e nt . 
W h er e d at es or ti m es ar e missi n g or p arti ally missi n g, A Es will b e ass u m e d t o b e tr e at m e nt-
e m er g e nt, u nl ess t h er e is cl e ar evi d e nc e (t hr o u g h c o m p aris o n of p arti al d at es/ti m es, s e e S ecti o n 
7. 3. 1 ) t o s u g g est t h at t h e A E st art e d pri or t o d osi n g. 
 
A Es will b e cl assifi e d i nt o t h e f oll o wi n g st u dy p h as es b as e d o n t h e o ns et d at e/ti m e of t h e A E aft er 
a ny i m p ut ati o ns:  
•  
Pr e -Tr e at m e nt P h as e: All A Es wit h o ns et d at e/ti m e pri or t o t h e first d os e of st u dy tr e at m e nt  
•  
Tr e at m e nt P h as e: All  A Es wit h o ns et d at e/ti m e at t h e ti m e of or aft er t h e first d os e of st u dy 
tr e at m e nt ( D a y 1) u p t o a n d i ncl u di n g t h e d at e of t h e l ast d os e of tr e at m e nt r ec ei v e d 
•  
F oll o w -u p P h as e: All A Es wit h o ns et d at e aft er t h e d at e of t h e l ast d os e of tr e at m e nt 
r ec eiv e d 
  
F or p artici p a nts w h o c o m pl et e 3 6 w e e ks  of d osi n g p er pr ot oc ol , t h e Tr e at m e nt P h as e will b e fr o m 
D a y 1 t o t h e W e e k 36 visit,  a n d t h e F oll o w -u p P h as e will st art aft er t h e Tr e at m e nt P h as e a n d l ast 
u ntil t h eir l ast d a y i n t h e st u dy . I n all c as es t h e d a y will b e ass u m e d t o st art at 0 0: 0 0 h o urs a n d e n d 
at 2 3: 5 9 h o urs. A dv ers e ev e nts occ urri n g i n b ot h t h e Tr e at m e nt P h as e a n d F oll o w -u p P h as e ar e 
cl assifi e d as tr e at m e nt e m er g e nt. 
 
F or p artici p a nts w h o w er e a d mi nist er e d activ e tr e at m e nt i n t h e p ar e nt st u dy, t h e P ar e nt Tr e at m e nt 
P h as e will b e d efi n e d fr o m t h e first d os e of I M P i n t h e p ar e nt st u dy u p t o t h e D ay 1 i n t his st u dy.  
 
T h e o ns et p h as e of all A Es will b e i ncl u d e d i n t h e r el ev a nt d at a listi n gs.  
6  
S a m pl e Siz e  
T h e s a m pl e siz e of t h e st u dy will b e d et er mi n e d b y t h e n u m b er of p artici p a nts w h o e nr ol  fr o m 
q u alif yi n g at o pic d er m atitis p ar e nt st u di es wit h E D P 1 8 1 5.  
 
7  
G e n er al C o nsi d er ati o ns  
7. 1  
A n al ysis P o p ul ati o ns  
7. 1. 1  
P artici p a nt A n al ysis P o p ul ati o ns  
7. 1. 1. 1  E nr oll e d P o p ul ati o n  
T h e e nr oll e d s et will c o nsist of all p arti cip a nts w h o si g n t h e I C F.  
 
7. 1. 1. 2  F ull A n al ysis  P o p ul ati o n  
T h e f ull a n alysis p o p ul ati o n will c o nsist of all p artici p a nts w h o r ec ei v e a ny I M P.  


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 1 9  of 7 5  
 
7. 1. 1. 3  Ot h er  P o p ul ati o n s 
Ot h er p ar e nt st u dy s p ecific a n alysis s ets m ay als o b e us e d i n i nt eri m a n alys es w hic h will b e d efi n e d 
by t h e s u bs et of p artici p a nts fr o m t h e F A S w h o w er e pr e vi o usly e nr oll e d fr o m t h e s p ecific p ar e nt 
st u di es or st u dy c o h orts. S uc h p o p ul ati o ns will b e n a m e d xxxxxx F ull A n alysis S et, w h er e xxxxxx 
st a n ds f or t h e st u dy s p ecific s u bs et i d e ntifi er. 
 
7. 1. 2  
D efi n e d D at a P oi nt S ets  
7. 1. 2. 1  D at a P oi nt S et 1 ( D P S 1)  
D P S 1 c o nsists of all o bs erv e d d at a c oll ect e d f oll o wi n g t h e first d os e of I M P i n t his st u dy u ntil 3 0 d a ys 
aft er t h e l ast d os e of I M P.  
N ot e, b as eli n e d at a will b e t a k e n fr o m t h e p ar e nt st u dy.  
 
7. 1. 2. 2  D at a P oi nt S et 2 ( D P S 2)  
D P S 2 c o nsists  of all o bs erv e d d at a c oll ect e d f oll o wi n g t h e first d os e of acti v e I M P, eit h er i n t h e 
p ar e nt st u dy or i n t his st u dy u ntil 3 0 d ays aft er t h e l ast d os e of I M P i n t his st u dy.  
 
7. 1. 2. 3  D at a P oi nt S et 3 ( D P S 3)  
D P S 3 c o nsists of all o bs erv e d d at a c oll ect e d at a sc h e d ul e d  visit i n t his st u dy.   
N ot e, c h a n g es fr o m b as eli n e will b e d eriv e d usi n g b as eli n e d at a fr o m t h e p ar e nt st u dy.  
 
7. 1. 2. 4  D at a P oi nt S et 4  ( D P S4 ) 
D P S 4 c o nsists of all o bs erv e d d at a c oll ect e d at a sc h e d ul e d visits i n t his st u dy or t h e p ar e nt st u dy f or 
p artici p a nts w h o e nt er t his st u dy.  
 
7. 1. 2. 5  D at a P oi nt S et 4 a  (D P S 4 a ) 
D P S 4 a is a s u bs et of D P S 4, excl u di n g a n y d at a c oll ect e d wit hi n 4 w e e ks aft er t h e us e of p er mitt e d 
r esc u e m e dic ati o ns f or at o pic d er m atitis or at a ny ti m e aft er t h e us e of pr o hi bit e d m e dic ati o ns f or 
at o pic d er m atitis.  
 
7. 1. 2. 6  D at a P oi nt S et 4 b  ( D P S4 b ) 
D P S 4 b is a s u bs et of D P S 4 f or r es p o n d er e n d p oi nts o nly, w h er e d at a c oll ect e d wit hi n 4 w e e ks aft er 
t h e us e of p er mitt e d r esc u e m e dic ati o ns f or at o pic d er m atitis, at a n y ti m e aft er t h e us e of 
pr o hi bit e d m e dic ati o ns f or at o pic d er m atitis, or at sc h e d ul e d e n d p oi nts aft er wit h dr a w al fr o m 
tr e at m e nt d u e t o tr e at m e nt-f ail ur e r el at e d r e as o ns (r el at e d A Es, l ac k of effic acy, r e q uir e m e nt f or 
alt er n at e ps ori asis t h er a py) will b e r e pl ac e d by ‘ n o n -r es p o n d er’. 
 
7. 1. 2. 7  D at a P o i nt S et 5 ( D P S 5) 
D P S 5 c o nsists of all o bs erv e d d at a c oll ect e d f oll o wi n g t h e first d os e of I M P i n t his st u dy.  
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 2 0  of 7 5  
7. 2  
C o v ari at es a n d S u b gr o u ps  
N o i nf er e nti al st atistic al t esti n g will b e p erf or m e d s o n o c o v ari at es will b e d efi n e d.  
 
7. 3  
Missi n g D at a  
U nl ess ot h er wis e s p e cifi e d as p art of t h e i nt erc urr e nt e v e nt str at e gy, missi n g d at a will n ot b e 
i m p ut e d. Im p ut ati o n of missi n g effic acy d at a d u e t o i nt erc urr e nt ev e nts will b e p erf or m e d  i n D P S 4 a 
a n d  D P S 4 b  as d escri b e d i n S ecti o n 7. 1. 2 . 
 
7. 3. 1  
P arti al D at es/ Ti m es  
P arti al d at es a n d ti m es f or A Es, m e dic al c o n diti o ns a n d c o nc o mit a nt m e dic ati o ns will b e i m p ut e d f or 
t h e p ur p os e of assi g ni n g st u dy p h as es a n d c alc ul ati n g d ur ati o n. Listi n gs will al w ays i ncl u d e t h e 
r e p ort e d d at e/ti m e i nf or m ati o n r at h er t h a n a ny i m p ut ati o ns. 
 
P arti al A E o ns et a n d c o nc o mit a nt m e dic ati o n st art d at es will b e i m p ut e d as f oll o ws:  
•  
If o nl y t h e m o nt h a n d y e ar ar e s p ecifi e d, a n d t h e m o nt h a n d y e ar of t h e st art of tr e at m e nt in 
2 0 8 ar e n ot t h e s a m e as t h e m o nt h a n d y e ar of t h e st art d at e, t h e n us e t h e 1 st of t h e m o nt h.  
•  
If o nl y t h e m o nt h a n d y e ar ar e s p ecifi e d, a n d t h e m o nt h a n d y e ar of t h e st art of tr e at m e nt i n 
2 0 8  ar e t h e s a m e as t h e m o nt h a n d y e ar of t h e st art d at e, t h e n us e t h e d at e of st art of 
tr e at m e nt. If t his r es ults i n a st art d at e aft er a k n o w n or p arti al e n d d at e, t h e n us e t h e 1 st of 
t h e m o nt h. 
•  
If o nl y t h e y e ar is s p ecifi e d, a n d t h e y e ar of t h e st art of tr e at m e nt i n 2 0 8 is n ot t h e s a m e as 
t h e y e ar of t h e st art d at e, t he n us e J a n u ar y 1 of t h e y e ar of t h e st art d at e.  
•  
If o nl y t h e y e ar is s p ecifi e d, a n d t h e y e ar of t h e st art of tr e at m e nt i n 2 0 8 is t h e s a m e as t h e 
y e ar of t h e st art d at e, t h e n us e t h e d at e of t h e st art of tr e at m e nt. If t his r es ults i n a st art 
d at e aft er a k n o w n or p arti al e n d d at e, t h e n us e J a n u ar y 1 of t h e y e ar of t h e st art d at e.  
•  
If t h e st art d at e is c o m pl et el y u nk n o w n, t h e n us e t h e d at e of t h e st art of tr e at m e nt i n 2 0 8. If 
t his r es ults i n a st art d at e aft er a k n o w n or p arti al e n d d at e, d o n ot i m p ut e t h e st art d at e. 
 
P arti al A E o ns et st art ti m es will b e i m p ut e d as f oll o ws:  
•  
If t h e act u al or i m p ut e d st art d at e is t h e s a m e as t h e 2 0 8 tr e at m e nt st art d at e, a n d t h e st art 
ti m e is c o m pl et el y missi n g, t h e n us e t h e ti m e of st art of tr e at m e nt. 
•  
If t h e act u al or i m p ut e d st art d at e is n ot t h e s a m e as t h e 2 0 8 tr e at m e nt st art d at e, a n d t h e 
st art ti m e is c o m pl et el y missi n g, t h e n us e 0 0: 0 0. 
•  
If t h e act u al or i m p ut e d st art d at e is t h e s a m e as t h e 2 0 8 tr e at m e nt st art d at e, a n d t h e st art 
ti m e is p arti ally missi n g  ( h h: X X) t h e n us e t h e f oll o wi n g: 
o  If t h e h o ur is t h e s a m e as t h e h o ur of t h e st art of tr e at m e nt ti m e t h e n us e t h e 
c o m pl et e ti m e of t h e st art of tr e at m e nt (i. e., b ot h h o urs a n d mi n ut es)  
o  If t h e h o ur is n ot t h e s a m e as t h e h o ur of t h e st art ti m e t h a n use h h : 0 0. 
•  
If t h e act u al or i m p ut e d st art d at e is n ot t h e s a m e as t h e 2 0 8 tr e at m e nt st art d at e, a n d t h e 
st art ti m e is p arti ally missi n g ( h h: X X) t h e n us e h h: 0 0. 
 
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 2 1  of 7 5  
P arti al m e dic al c o n diti o ns st art d at es will b e i m p ut e d as f oll o ws:  
•  
If o nl y t h e m o nt h a n d y e ar are s p ecifi e d, t h e n us e t h e 1st d ay of t h e m o nt h.  
•  
If o nl y t h e y e ar is s p ecifi e d, t he n us e J a n u ar y 1st of t h at y e ar.  
•  
If t h e st art d at e is c o m pl et el y u nk n o w n, d o n ot i m p ut e t h e start  d at e.  
 
P arti al A E r es ol uti o n, m e dic al c o n diti o n st o p d at es a n d c o nc o mit a nt m e dic ati o n st o p d at es a n d d at e 
l ast s m ok e d will b e i m p ut e d as f oll o ws: 
•  
If t h e ev e nt, c o n diti o n or m e dic ati o n is fl a g g e d as o n g oi n g, d o n ot i m p ut e t h e st o p d at e. 
•  
If o nl y t h e m o nt h a n d y e ar ar e s p ecifi e d, t h en us e t h e l ast d a y of t h e m o nt h.  
•  
If o nl y t h e y e ar is s p ecifi e d, t he n us e D ec e m b er 3 1 of t h at y e ar.  
•  
If t h e st o p d at e is c o m pl et el y u n k n ow n, d o n ot i m p ut e t h e st o p d at e.  
 
P arti al A E r es ol uti o n a n d c o nc o mit a nt m e dic ati o n st o p ti m es will b e i m p ut e d as f oll o ws:  
•  
If t h e act u al or i m p ut e d st o p d at e is n o n-missi n g, a n d t h e st o p ti m e is c o m pl et ely missi n g, 
t h e n us e 2 3: 5 9 o n t h at d at e. 
•  
If t h e act u al or i m p ut e d st o p d at e is n o n-missi n g, a n d t h e st o p ti m e is p arti ally missi n g, t h e n 
h h: 5 9 f or missi n g  mi n ut es.  
•  
If t h e act u al or i m p ut e d st o p d at e is missin g, d o n ot i m p ut e t h e st o p ti m e.  
 
7. 3. 2  
A d v ers e E v e nt I nf or m ati o n  
A Es wit h missi n g r el ati o ns hi p will b e c o nsi d er e d ‘ R el at e d’ f or s u m m ary p ur p os es b ut r ec or d e d as 
missi n g i n t h e listi n gs.  
 
7. 4  
St u d y D eli v eri es  
7. 4. 1  
E arl y St o p pi n g  
I n t h e ev e nt t h at s o m e or all of t h e c o h orts st o p t h e st u dy e arly, it m ay b e d eci d e d t o m ak e a si n gl e 
d eliv ery f or all st u dy c o h orts  wit h r e d uc e d n u m b er of T FLs . 
 
7. 4. 2  
P ur p os e of St u d y D eli v eri es  
I nt eri m s af ety a n d effic acy a n al ys es m ay b e p erf or m e d t hr o u g h o ut t h e lif e cycl e of t h e st u dy as 
r e q uir e d f or o n g oi n g e val u ati o n of t h e ris k b e n efit pr ofil e of E D P 1 8 1 5. T h es e m a y i ncl u d e eit h er all 
p artici p a nts e nr oll e d i n t h e st u dy or us e a s u bs et of p artici p a nts w h o tr a nsiti o n e d t o t his st u dy fr o m 
a s p ecific p ar e nt st u dy  or a s p ecific p ar e nt st u dy c o h ort . A n al ys es p erf or m e d o nc e p artici p a nts fr o m 
a s p ecific p ar e nt st u dy or a s p ecific p ar e nt st u dy c o h ort c o m pl et e 2 0 8 st u dy will b e c o nsi d er e d as 
fi n al d eliv eri es.  
 
All a n al ys es will als o i nc or p or at e d at a c oll ect e d o n t h e p ar e nt at o pic d er m atitis E D P 1 8 1 5 st u di es 
w hic h f e e d i n t o t his st u dy.  
 
7. 4. 3  
Pl a n n e d Sc h e d ul e of D eli v eri es  
T h e  i nt eri m a n d fi n al  a n al ys e s will  b e p erf o rm e d  t hr o u g h o ut t h e lif e cycl e of t h e st u dy as r e q uir e d.  


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 2 2  of 7 5  
 
At a mi ni m u m, t h er e will b e E D P 1 8 1 5 -2 0 7 p ar e nt -st u dy s p ecific a n alysis p erf or m e d aft er all 
p artici p a nts f r o m  
•  
2 0 7 c o h orts 1-3  (D eliv ery 1)  
•  
2 0 7 c o h ort 4  (D eliv ery 2)  
h av e c o m pl et e d t his st u dy.  
 
A n al ysis will b e r estrict e d t o p artici p a nts fr o m t h e c orr es p o n di n g c o h orts  i n t h e p ar e nt st u dy w h o 
tr a nsiti o n e d t o t his st u dy.  
 
7. 4. 4  
E n d p oi nts t o b e I ncl u d e d i n t h e St u d y D eli v eri es  
All e n d p oi nts will b e i ncl u d e d i nt o t h e p ar e nt -st u dy s p ecific a n alyse s.  
 
7. 4. 5  
A dj ust m e nt of C o nfi d e nc e I nt er v als a n d p -v al u es  
N o i nf er e nti al c o m p aris o ns of effic acy will b e p erf or m e d s o  n o a dj ust m e nts f or al p h a -s p e n di n g ar e 
r e q uir e d. 
 
7. 4. 6  
Pr actic al M e as ur es t o Mi ni mis e Bi as  
T his is a n OL E  st u dy wit h all p artici p a nts t a ki n g E D P 1 8 1 5 c a ps ul es s o n o bli n di n g is r e q uir e d f or t h e 
st u dy m e dic ati o n i n t his st u dy. H o w e v er, i nv esti g at ors a n d p artici p a nts will c o nti n u e t o b e bl i n d e d t o 
t h e p artici p a nt’s  tr e at m e nt assi g n m e nt i n t h e p ar e nt st u dy i n or d er t o mi ni miz e bi as. 
 
U n bli n d e d r es ults will n ot b e s h ar e d wit h a ny st u dy sit e st aff or p artici p a nts.    
 
7. 4. 7  
D oc u m e nt ati o n of St u d y D eli v eri es  
T h e st u dy is o p e n l a b el b ut  t h e   
 t e am will b e u n bli n d e d t o t h e tr e at m e nt assi g n m e nt o nl y 
fr o m t h e ti m e of p ar e nt st u dy D BL.  
As t h e p ati e nts’ assi g n m e nts d at a will b e o nl y a v ail a bl e f or  
 aft er  t h e p ar e nt st u dy D BL, 
t h er e is n o ris k of u n bli n di n g a n d t h er e will b e n o s e p ar at e u n bli n d e d t e a m. A ny i nt eri m a n alysis  
d at a will b e h el d i n t h e n o n -r estrict e d fil e str uct ur e a v ail a bl e t o t h e w h ol e   
 t e a m  w orki n g o n 
2 0 8 st u dy . 
7. 5  
M ulti -c e ntr e St u di es 
R es ults will b e pr es e nt e d f or all c e ntr es c o m bi n e d.  
 
7. 6  
M ulti pl e T esti n g  
T h e f oc us of this st u dy is o n s af ety, s p ecific ally t h e i nci d e nc e a n d r at e of T E A Es p er 1 0 0-p ati e nt 
y e ars, a n d as s uc h n o a dj ust m e nts  w ill b e m a d e f or m ulti pl e t esti n g i n t his st u dy . 
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 2 3  of 7 5  
7. 7  
Visit Wi n d o ws  
All d at a will b e r e p ort e d acc or di n g t o n o mi n al visits . F or ex a m pl e, if a W e e k 4 visit occ urr e d o n D a y 
3 0  i nst e a d of t h e n o mi n ally ex p ect e d D a y 2 8  it will b e r e p ort e d a n d i ncl u d e d i n t h e s u m m ary 
st atistics/st atistic al a n al ys es f or W e e k 4.  
 
Sc h e d ul e d visits w hic h occ ur o utsi d e t h e pr ot oc ol -s p ecifi e d visit wi n d o w ( e. g., if t h e W ee k 4 visit 
occ urr e d o n D a y 3 2, o utsi d e of t h e D ay 2 5 -3 1  wi n d o w), t his will b e n ot e d as a pr ot oc ol d evi ati o n b ut 
d at a c oll ect e d will still b e i ncl u d e d i n all s u m m ary a n d a n alysis t a bl es.  
 
U nsc h e d ul e d visits a n d E arl y T er mi n ati o n visit will n ot b e i ncl u d e d i n s u m m ary or a n al ysis t a bl es, 
u nl ess t h ey ar e b as eli n e m e as ur e m e nts  or  pr ovi d e d at a t o w ar ds a  s af et y e n d p oi nt w hic h l o oks at 
w orst -c as e p ost-b as eli n e .  
 
All listi n gs will i ncl u d e all c oll ect e d d at a ev e n if t h e y ar e fr o m a n u nsc h e d ul e d visit.  
 
8  
S u m m ar y of St u d y D at a  
All c o nti n u o us v ari a bl es will b e s u m m ariz e d usi n g t h e f oll o wi n g d escri ptiv e st atistics: n ( n o n -missi n g 
s a m pl e siz e), m e a n, S D, m e di a n, m axi m u m, a n d mi ni m u m. T h e fr e q u e ncy a n d p erc e nt a g es ( b as e d o n 
t h e n o n-missi n g s a m pl e siz e) of o bs er v e d l ev els will b e r e p ort e d f or all c at e g oric al m e as ur es.  
 
I n g e n er al, all d at a will b e list e d, s ort e d b y gr o u p  ( 1, 2, a n d 3 ), c o u ntry, sit e n u m b er a n d p artici p a nt 
n u m b er.  R el ev a nt listi n gs will i ncl u d e w h et h er t h e ass ess m e nt w as p erf or m e d a n d t h e d at e, st u dy 
d a y/visit a n d ti m e of t h e ass ess m e nt as a p plic a bl e.   
 
A ny st u dy p o p ul ati o n or s af et y t a bl es, listi n gs or fi g ur es  t h at dis pl a y tr e at m e nt will al w ays pr es e nt 
t h e act u al tr e at m e nt r ec eiv e d r at h er t h a n t h e pl a n n e d tr e at m e nt as t h e pri m ar y o bj ectiv e is t o 
ev al u at e t h e s af et y of E D P 1 8 1 5. F or effic acy s u m m ari es pl a n n e d tr e at m e nt will b e us e d.  
 
U nl ess ot h er wis e s p ecifi e d b el o w, all s u m m ar y t a bl es will b e str uct ur e d wit h a c ol u m n f or e ac h 
gr o u p  ( gr o u ps 1 a n d 2 will b e pres e nt e d i n 2 0 7 c o h orts 1 -3 d eli v er y  a n d gr o u p 3 will b e pr es e nt e d i n 
2 0 7 c o h ort 4 d eli v er y ) a n d a n a d diti o n al ‘ T ot al’ c ol u m n w hic h c o nt ai ns all p ati e nts i ncl u d e d i n t h e 
r el ev a nt i nt eri m or fi n al a n al ysis. 
 
T h e l a b els pr es e nt e d f or e ac h gr o u p will b e as  f oll o ws: 
•  
Gr o u p 1 = 1. 6x 1 0 1 1  T C P D  
•  
Gr o u p 2 = 6 . 4x 1 0 1 1 T C P D  
•  
Gr o u p 3 = 8. 0 x 1 0 1 0 T C P D  
 
F or s u m m ari es of s af ety e n d p oi nts t h at l o o k at t h e p eri o d d efi n e d si nc e first d os e of acti v e I M P 
eit h er i n t his st u dy or t h e r el e v a nt p ar e nt st u dy, t h e d at a  will b e or d er e d  a n d l a b ell e d as f oll o ws:  
•  
1. 6x 1 0 1 1 T C P D  ( F or 2 0 7 c o h orts 1 -3 d eli v er y  o nly)  
•  
6 . 4x 1 0 1 1 T C P D  ( F or 2 0 7 c o h orts 1 -3 d eli v er y  o nly)  




St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 2 5  of 7 5  
T h e list of o ut p uts pr o d uc e d i n t h e c as e t h e st u dy is st o p p e d e arly ar e pr ovi d e d i n   1 6 A p p e n dix 1: List 
of T a bl es, Fi g ur es a n d Listi n gs. 
 
 
8. 2  
S t u d y Dis p ositi o n  
C o m pl eti o n/ wit h dr a w al fr o m t h e st u dy a n d c o m pl eti o n/ disc o nti n u ati o n fr o m tr e at m e nt, t o g et h er 
wit h r e as o ns f or wit h dr a w al fr o m t h e st u dy or disc o nti n u ati o n fr o m tr e at m e nt will b e list e d a n d t h e 
f oll o wi n g will als o b e t a b ul at e d: 
•  
N u m b er a n d p erc e nt a g e of p artici p a nts w h o c o m pl et e d t h e st u dy  
•  
N u m b er a n d p erc e nt a g e of p artici p a nts wit h dr a w n fr o m t h e st u dy a n d t h e r e p ort e d r e as o n 
f or wit h dr a w al  
•  
N u m b er a n d p erc e nt a g e of p artici p a nts w h o c o m pl et e d t h e 3 6 -w e e k tr e at m e nt p eri o d   
•  
N u m b er a n d p erc e nt a g e of p artici p a nts w h o disc o nti n u e d tr e at m e nt e arl y a n d r e as o n f or 
disc o nti n u ati o n   
 
F or p artici p a nts  w h o f ail t o m e et t h e eli gi bility crit eri a t h e r e as o ns f or f ail ur e, i ncl u di n g t h e 
i ncl usi o n/ excl usi o n crit eri a t h at w er e n ot m et will b e s u m m ari ze d a n d list e d.  
 
T h e n u m b er a n d p e rc e nt a g e of p artici p a nts e nr oll e d wit hi n e ac h r e gi o n, c o u ntry a n d sit e will b e 
s u m m arize d.  
 
F or t h e e nr oll e d p o p ul ati o n, t h e n u m b er a n d p erc e nt a g e of p artici p a nts i n e ac h a n al ysis p o p ul ati o n 
will b e pr es e nt e d.  I ncl usi o n/ excl usi o n i n e ac h st u dy p o p ul ati o n will als o b e list e d, t o g et h er wit h 
r e as o ns f or excl usi o n. 
 
T h e n u m b er a n d p erc e nt a g e of p artici p a nts wit h d at a a v ail a bl e f or e ac h sc h e d ul e d visit (i ncl u di n g 
t h e e arly t er mi n ati o n visit) will b e s u m m ari ze d.  
 
Miss e d visits d u e t o C O VI D -1 9 will als o b e s u m m ari ze d a n d list e d.  
 
8. 3  
Pr ot oc ol D e vi ati o ns  
T h e n u m b er a n d p erc e nt a g e of p artici p a nts i n t h e f ull a n al ysis p o p ul ati o n wit h at l e ast o n e  
si g nific a nt pr ot oc ol d evi ati o n will b e s u m m ari ze d  by d e vi ati o n c at e g or y .  
 
All pr ot oc ol d evi ati o ns will als o b e list e d. 
 
8. 4  
D e m o gr a p hic a n d B as eli n e V ari a bl es  
D e m o gr a p hy d at a of a g e, s ex, r ac e, a n d et h nicity  will b e s u m m ari ze d a n d list e d t o g et h er wit h h ei g ht, 
w ei g ht , a n d B MI a t t h e p ar e nt st u dy b as eli n e. 
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 2 6  of 7 5  
8. 5  
M e dic al Hist or y  
M e dic al hist ory a n d c o nc urr e nt ill n ess es will b e  c a pt ur e d a n d c o d e d usi n g t h e M e dic al Dicti o n ary f or 
R e g ul at ory Acti viti es ( M e d D R A ®).  T h e  dicti o n ary will b e u p d at e d t hr o u g h t h e lif e of t h e st u dy wit h 
v ersi o n  2 4. 0 us e d i niti ally.  
 
P ar e nt st u dy m e dic al hist ory will b e us e d i n t h e s u m m ari es t o g et h er wit h 2 0 8 d at a t o pr es e nt all 
p ast a n d c o nc urr e nt m e dic al hist ory. P ar e nt st u dy m e dic al hist ory w o n’t b e r ec o d e d if t h e M e d D R A  
will b e u p d at e d t hr o u g h t h e lif e of 2 0 8 st u dy, t h e dicti o n ar y fr o m t h e ti m e of t h e p ar e nt st u dy d at a 
b as e l oc k will b e us e d.  
 
C o nc urr e nt  ill n ess es a n d m e dic al c o n diti o ns will b e cl assifi e d as ‘c urr e nt’ if t h e e n d d at e is o n or 
aft er t h e d at e of first d os e of st u dy dr u g, or t h e c o n diti o n h as b e e n m ar k e d as o n g oi n g.  Ot h er wis e,  
t h e y will b e cl assifi e d as ‘ p ast’. 
 
P ast a n d c urr e nt m e dic al his t ory will b e s u m m arize d s e p ar at ely b y Syst e m Or g a n Cl ass ( S O C) a n d 
Pr ef err e d T er m ( P T) .  S u m m ar y t a bl es will c o nt ai n t h e n u m b er a n d p erc e nt a g e of p ati e nts. A p ati e nt 
w h o h as m ulti pl e c o n diti o ns i n t h e s a m e S O C or wit h t h e s a m e P T will b e c o u nt e d o nl y o nc e i n t h e 
p ati e nt c o u nts. M e dic al hist or y s u m m ari es will b e s ort e d b y t h e i nt er n ati o n ally a gr e e d S O C or d er 
(T a bl e 1 0 ) a n d d ecr e asi n g fr e q u e nc y of P T wit hi n S O C i n t h e T ot al c ol u m n. 
 
All m e dic al hist or y d at a will b e list e d.  
 
8. 6  
Pri or a n d C o nc o mit a nt  M e dic ati o ns  
M e dic ati o ns c oll ect e d d uri n g t h e 2 0 8 st u dy will b e  c o d e d acc or di n g t o t h e W orl d H e alt h 
Or g a niz ati o n Dr u g Dicti o n ar y ( W H O D D) . T h e dicti o n ary will b e u p d at e d t hr o u g h t h e lif e of t h e st u dy 
wit h t h e v ersi o n d at e d 0 1 M ar 2 0 2 1 us e d i niti all y . M e dic al pr oc e d ur es will n ot b e c o d e d.  
 
P ar e nt st u dy m e dic ati o ns d at a will b e us e d i n t h e s u m m ari es t o g et h er wit h 2 0 8 d at a t o pr es e nt all 
pri or a n d c o nc o mit a nt m e dic ati o ns fr o m t h e w h ol e p eri o d b ef or e a n d d uri n g 2 0 8 st u dy. P ar e nt 
st u dy m e dic ati o ns w o n’t b e r ec o d e d if t h e dicti o n ary will b e u p d at e d t hr o u g h t h e lif e of 2 0 8 st u dy, 
t h e dicti o n ar y fr o m t h e ti m e of t h e p ar e nt st u dy d at a b as e l oc k will b e us e d.  
 
C o nc o mit a nt m e dic ati o ns ar e d efi n e d as a n y m e dic ati o ns t ak e n d uri n g t h e 2 0 8 tr e at m e nt p eri o d or 
f oll o w-u p p eri o d aft er tr e at m e nt.  T his i ncl u d es a ny m e dic ati o ns st art e d b ef or e t h e 2 0 8 first d os e 
a n d o n g oi n g aft er t h e first d os e. Pri or m e dic ati o ns ar e d efi n e d as a ny m e dic ati o n t a k e n b ef or e or 
d uri n g t h e p ar e nt st u dy w hic h w er e st o p p e d b ef or e t h e first d os e of  2 0 8  st u dy m e dic ati o n.  
 
Missi n g a n d p arti al st art a n d st o p d at es will b e i m p ut e d usi n g t h e r ul es s p ecifi e d i n S ecti o n 7. 3. 1  
b ef or e cl assifyi n g t h er a pi es as pri or or c o nc o mit a nt. If t h e cl assific ati o n is still a m bi g u o us aft er 
missi n g a n d p arti al d at es h a v e b e e n i m p ut e d, t h e n t h e m e dic ati o n will b e c o nsi d er e d c o nc o mit a nt.  
 
M e dic ati o ns will b e s u m m ari ze d by  W H O D D A n at o mic al M ai n Gr o u p (L ev el 1), T h er a p e utic S u b gr o u p 
(L ev el 2) a n d pr ef err e d t er m.  T h e s u m m ari es will r e p ort i nci d e nc e wit hi n e ac h r el e v a nt l ev el s o t h at 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 2 7  of 7 5  
a p artici p a nt t aki n g m ulti pl e m e dic ati o ns c o d e d t o t h e s a m e r el e v a nt L e v el 1, L ev el 2 or pr ef err e d 
t er m w o ul d o nly be c o u nt e d o nc e wit hi n t h e i nci d e nc e c o u nt f or t h at l ev el or t er m.  
 
S e p ar at e s u m m ari es will b e pr o d uc e d f or e ac h of t h e f oll o wi n g:  
•  
All co nc o mit a nt m e dic ati o ns  
•  
C o nc o mit a nt m e dic ati o ns st art e d b ef or e or d uri n g  t h e p ar e nt st u dy  
•  
C o nc o mit a nt m e dic ati o ns st art ed d uri n g t h e 2 0 8 tr e at m e nt p eri o d  
•  
C o nc o mit a nt m e dic ati o ns st art e d d uri n g t h e 2 0 8 f oll o w-u p p eri o d  
 
All pri or a n d c o nc o mit a nt m e dic ati o ns will b e list e d.  
 
C at e g oriz ati o n of all c o nc o mit a nt m e dic ati o ns pr escri b e d d uri n g t h e st u dy will b e d o n e b y E v el o 
cli nici a n i n or d er t o i d e ntify T C S/ T CI r esc u e t h er a py, a nti micr o bi al r esc u e t h er a py a n d pr o hi bit e d 
m e dic ati o ns . 
 
8. 7  
Tr e at m e nt C o m pli a nc e  
Tr e at m e nt c o m pli a nc e will b e s u m m arize d f or t h e w h ol e 3 6 -w e e k tr e at m e nt p eri o d.   
 
S u m m ary st atistics ( n, m e a n, S D, m e di a n a n d r a n g e) will b e pr o d uc e d t o g et h er wit h t h e n u m b er a n d 
p erc e nt a g e of p artici p a nts wit hi n e ac h of t h e c at e g ori es d efi n e d i n S ecti o n 5. 3. 2. 1 .  P erc e nt a g es will 
us e t h e n u m b er of p artici p a nts w h o st art e d t h e tr e at m e nt p eri o d as t h e d e n o mi n at or.  
 
D at a fr o m t h e d osi n g l o g a n d t h e c alc ul at e d tr e at m e nt c o m pli a nc e will als o b e list e d.  
 
8. 8  
E m olli e nt  C o m pli a nc e  
E m olli e nt  c o m pli a nc e will b e s u m m arize d f or t h e w h ol e tr e at m e nt a n d  f oll o w-u p p eri o d s. 
 
S u m m ary st atistics ( n, m e a n, S D, m e di a n a n d r a n g e) will b e pr o d uc e d t o g et h er wit h t h e n u m b er a n d 
p erc e nt a g e of p artici p a nts wit hi n e ac h of t h e c at e g ori es d efi n e d i n S ecti o n  5. 3. 2. 2 .  P erc e nt a g es will 
us e t h e n u m b er of p artici p a nts w h o st art e d t h e p eri o d as t h e d e n o mi n at or.  
 
D at a fr o m t h e d aily di ar y  a n d t h e c alc ul at e d e m olli e nt  c o m pli a nc e will als o b e list e d. 
 
9  
Pri m ar y  S af et y A n al ysis  
9. 1  
E arl y St o p pi n g  
I n t h e ev e nt t h at t h e st u dy is st o p p e d e arly a n d o nl y a r e d uc e d a m o u nt of o ut p uts ar e n e e d e d, 
s af et y d at a will o nl y b e r e p ort e d f or t h e p eri o d b e gi n ni n g wit h t h e first d os e of acti v e I M P i n t his 
st u dy. O nly i nci d e nc e a n d n u m b er of ev e nts will b e pr es e nt e d f or t h e f oll o wi n g c at e g ori es:  
•  
T E A Es  
•  
S eri o us T E A Es  
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 2 8  of 7 5  
D at a will b e pr es e nt e d as c oll ect e d, n o i m p ut ati o ns or d at a excl usi o n will b e m a d e.  
 
T h e list of o ut p uts pr o d u c e d i n t h e c as e t h e st u dy is st o p p e d e arly ar e pr ovi d e d i n  1 6 A p p e n dix 1: List 
of T a bl es, Fi g ur es a n d Listi n gs. 
 
9. 2  
Pri m ar y Esti m a n d of t h e Pri m ar y O bj ecti v e  
 
S af et y d at a will b e r e p ort e d f or t w o p eri o ds:  
•  
T h e p eri o d b e gi n ni n g wit h t h e first d os e of activ e I M P i n t his st u dy  
•  
T h e p eri o d b e gi n ni n g wit h t h e first d os e of activ e I M P acr oss t his st u dy a n d t h e p ar e nt st u dy 
 
T h e pri m ar y s af ety e n d p oi nts will b e t h e i nci d e nc e a n d r at e p er 1 0 0 p ati e nt -y e ars f or:  
•  
T E A Es  
•  
T E A Es of Gr a d e 2 or a b ov e  
•  
T E A Es of Gr a d e 3 or a b ov e  
•  
S eri o us T E A Es  
•  
F at al T E A Es  
•  
T E A Es c a usi n g disc o nti n u ati o n of st u dy dr u g  
•  
St u dy dr u g r el at e d T E A Es ( d efi n e d b y a n i nv esti g at or ass ess m e nt of p ossi bl e, pr o b a bl e, or 
d efi nit e r el ati o ns hi p t o I M P)  
•  
St u dy dr u g r el at e d T E A Es of Gr a d e 2 or a b ov e  
•  
St u dy dr u g r el at e d T E A Es of Gr a d e 3 or  a b ov e  
•  
St u dy dr u g r el at e d s eri o us T E A Es  
•  
St u dy dr u g r el at e d f at al T E A Es  
•  
St u dy dr u g r el at e d T E A Es c a usi n g disc o nti n u ati o n of st u dy dr u g  
 
9. 2. 1  
Esti m a n ds  
T h e pri m ar y s af ety esti m a n ds will us e t h e F A S  or t h e p ar e nt st u dy s p ecific F A S f or t h e st u dy/c o h ort 
s p ecific a nalysis . 
Tr e at m e nt c o n diti o n: act u al tr e at m e nt r ec ei v e d will b e c o nsi d er e d.  
P o p ul ati o n s u m m ar y m e as ur e of i nt er est:  
•  
F or t h e e n d p oi nts l o o ki n g at t h e p eri o d d efi n e d b y t his st u dy o nl y - t h e i nci d e nc e a n d r at e 
p er 1 0 0 p ati e nt -y e ars of e ac h c at e g or y of T E A Es  ( D P S 1) 
•  
F or t h e e n d p oi nts l o o ki n g at t h e p eri o d d efi n e d si nc e first d os e of t h e activ e I M P i n t his 
st u dy a n d t h e r el ev a nt p ar e nt st u dy - t h e r at e p er 1 0 0 p ati e nt-y e ars of e ac h c at e g or y of 
T E A Es by tr e at m e nt gr o u p  ( D P S 2) 
 
I nt erc urr e nt e v e nts will b e acc o u nt e d f or i n t h e f oll o wi n g m a n n er: 




St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 3 0  of 7 5  
1 0. 2  S ec o n d ar y  Effic ac y A n al ysis  
1 0. 2. 1  R es p o n d er A n al ysis  
1 0. 2. 1. 1  Esti m a n ds  
T h e k e y s ec o n d ar y r es p o ns e e n d p oi nts will b e ev al u at e d at all sc h e d ul e d visits  a n d ar e as f oll o ws:  
•   
E A SI -5 0, E A SI -7 5, E A SI -9 0  
•   
I G A of 0 or 1 wit h a ≥2-p oi nt i m pr o v e m e nt fr o m b as eli n e  
•   
I G A of 0 or 1 
•   
B S A -5 0, B S A -7 5  
•   
S C O R A D -3 5, S C O R A D -5 0, S C O R A D -7 5  
•   
I m pr ov e m e nt of ≥4 p oi nts i n P O E M sc or e fr o m b as eli n e * 
 
T h e ot h er s ec o n d ar y e n d p oi nts ar e:  
•   
I G A of 0  
•   
B S A ≤3 %  
•   
I m pr ov e m e nt of ≥4 p oi nts i n DL QI fr o m b as eli n e * 
•   
I m pr ov e m e nt of ≥2 p oi nts i n P P-N R S sc or e fr o m b as eli n e * 
•   
I m pr ov e m e nt of ≥4 p oi nts i n P P-N R S sc or e fr o m b as eli n e *  
•   
I m pr ov e m e nt of ≥2 p oi nts i n S D-N R S sc or e fr o m b as eli n e *  
 
*  Of t h os e wit h a  r el e v a nt sc or e of ≥2/ 4 at b as eli n e  
 
T h e p o p ul ati o n s u m m ar y m e as ur e of i nt er est  f or all r es p o ns e estim a n ds  will b e t h e p erc e nt a g e of 
p artici p a nts wit h t h e r el ev a nt r es p o ns e  at e ac h visit . 
 
I nt erc urr e nt e v e nts f or r es p o ns e e n d p oi nts will b e acc o u nt e d f or i n t h e f oll o wi n g m a n n er:  
 




St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 3 2  of 7 5  
All r es p o ns e s ec o n d ary e n d p oi nts  will b e a n alys e d wit h a r es p o ns e esti m a n d 1 ( D P S 4 b) . K e y 
s eco n d ary e n d p oi nts will b e als o a n alys e d wit h s u p pl e m e nt ary r es p o ns e esti m a n ds 1 a n d 2 ( D P S 4 
a n d D P S 4 a).   
 
 
1 0. 2. 1. 2  A n al ytic al A p pr o ac h  
S u m m ary  t a b ul ati o ns of fr e q u e nc y a n d p erc e nt a g e of p artici p a nts wit hi n e ac h c at e g ory will b e 
pr es e nt e d  at e ac h sc h e d ul e d visit t h at t h e v ari a bl e is r ec or d e d. T h e  f oll owi n g visits s h o ul d b e 
pr es e nt e d  u nl ess o t h er wis e st at e d: B as eli n e, 2 0 7 W e e k 4, 8, 1 2, 1 6 (l a b ell e d as “ 2 0 7 / W e e k X”) a n d 
2 0 8 w e e k 4, 8, 1 2, 1 6, 2 4, 3 6, 4 0 (l a b ell e d as “ 2 0 8 / W e e k X”).  
 
Fi g ur es f or t h e pr o p orti o n of p artici p a nts ac hi evi n g r es p o ns e o v er ti m e f or e ac h of t h e crit eri a will b e 
cr e at e d f or t h e s a m e sc h e d ul e d visits as s u m m ari es . 
 
1 0. 2. 2  C o nti n u o us V ari a bl es A n al ysis  
1 0. 2. 2. 1  Esti m a n ds  
T h e s ec o n d ary c o nti n u o us e n d p oi nts ar e as f oll o ws:  
•  
C h a n g e a n d p erc e nt a g e c h a n g e fr o m b as eli n e i n E A SI sc or e  
•  
C h a n g e a n d p erc e nt a g e c h a n g e fr o m b as eli n e i n I G A * B S A  
•  
C h a n g e a n d p erc e nt a g e c h a n g e fr o m b as eli n e i n B S A 
•  
C h a n g e a n d p erc e nt a g e c h a n g e fr o m b as eli n e i n S C O R A D sc or e  
•  
C h a n g e a n d p erc e nt a g e c h a n g e fr o m b as eli n e i n DL QI sc or e  
•  
C h a n g e a n d p erc e nt a g e c h a n g e fr o m b as eli n e i n P O E M sc or e  
•  
C h a n g e fr o m b as eli n e i n P P -N R S *  
•  
C h a n g e fr o m b as eli n e i n  S D -N R S *  
 
* T h e sc or e at e ac h visit is c alc ul at e d as t h e m e a n d aily sc or e f or t h e 7 d ays pri or t o a n d i ncl u di n g t h e 
visit d at e. At l e ast 4 d aily sc or es m ust b e a v ail a bl e f or t h e sc or e at t h e r el ev a nt visit t o b e c o nsi d er e d 
ev al u a bl e.   
 
T h e p o p ul ati o n s u m m a r y m e as ur e of i nt er est will b e t h e m e a n at e ac h sc h e d ul e d visit. 
 
I nt erc urr e nt e v e nts f or c o nti n u o us esti m a n d 1  will b e acc o u nt e d f or i n t h e f oll o wi n g m a n n er:  












St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 3 8  of 7 5  
1 1. 1  E arl y St o p pi n g  
I n t h e ev e nt t h at t h e st u dy is st o p p e d e arly a n d o nl y a r e d uc e d a m o u nt of o ut p uts ar e n e e d e d, 
s af et y d at a will o nl y b e r e p ort e d f or t h e p eri o d b e gi n ni n g wit h t h e first d os e of acti v e I M P i n t his 
st u dy. 
 
A d diti o n ally t o t h e pri m ar y s af ety e n d p oi nts, o nl y t h e n o n -s eri o us T E A Es will b e s u m m ariz e d b y S O C 
a n d P T, h o w e v er, P Ts will b e pr es e nt e d o nl y i n c as e of T E A Es r e p ort e d by at l e ast 5 % of p artici p a nts 
i n a n y tr e at m e nt gr o u p. 
 
D at a will b e pr es e nt e d as c oll ect e d, n o i m p ut ati o ns or d at a excl usi o n will b e m a d e.  
 
T h e list of o ut p uts pr o d uc e d i n t h e c as e t h e st u dy is st o p p e d e arly ar e pr ovi d e d i n  1 6 A p p e n dix 1: List 
of T a bl es, Fi g ur es a n d Listi n gs. 
 
 
1 1. 2  E xt e nt of E x p os ur e  
T h e d ur ati o n of ex p os ur e ( d a ys) a n d n u m b er of d os es t a k e n will b e s u m m ariz e d usi n g s u m m ar y 
st atistics f or c o nti n u o us d at a. T w o s u m m ar y t a bl es  will b e pr o d uc e d, o n e f or t h e d ur ati o n  of 
ex p os ur e fr o m first d os e i n t his st u dy a n d o n e fr o m t h e first d os e of activ e tr e at m e nt acr oss t his 
st u dy a n d t h e p ar e nt st u dy.  
 
F or t h e 2 0 8 s p ecific s u m m ar y t h e n u m b er a n d p erc e nt a g e of p artici p a nts wit h at l e ast 4, 8, 1 2,  1 6 , 
2 4  a n d 3 6 w e e ks ( 2 8, 5 6, 8 4,  1 1 2 , 1 6 8, 2 5 2  d a ys r es p ecti v ely) of ex p os ur e will als o b e pr es e nt e d.  
 
F or t h e 2 0 8 a n d p ar e nt st u dy s u m m ary t h e n u m b er a n d p erc e nt a g e of p artici p a nts wit h at l e ast 1 6 , 
2 0 , 2 4, 2 8, 3 2, 4 0 a n d 5 2 w e e ks (1 1 2 , 1 4 0, 1 6 8, 1 9 6, 2 2 4, 2 8 0, 3 6 4 d ays r es p ecti v el y) of ex p os ur e will 
als o b e pr es e nt e d . 
 
T h e t ot al ex p os ur e p er 1 0 0 p ati e nt -y e ars will als o b e s u m m aris e d f or e ac h tr e at m e nt gr o u p f or b ot h 
s u m m ari es. 
 
Tr e at m e nt st art a n d st o p d at es, ex p os ur e d ur ati o n ( d a ys), n u m b er of d os es a d mi nist er e d , n u m b er of 
c a ps ul es t ak e n a n d r e as o ns f or d os e a dj ust m e nts a n d d os e i nt err u pti o ns will b e list e d b y p artici p a nt.  
 
1 1. 3  A d v ers e E v e nts  
I n t his st u dy adv ers e e v e nts will b e r e p ort e d fr o m t h e d at e of si g n e d i nf or m e d c o ns e nt a n d t hr o u g h 
t h e W e e k 36 visit u p t o 3 0 d a ys aft er t h e l ast d os e of I M P . A dv ers e eve nts occ urri n g  aft er 3 0  d ays 
p ost -tr e at m e nt w o ul d o nly b e r e p ort e d if t h e i n v esti g at or c o nsi d ers it t o b e r el at e d t o t h e st u dy 
tr e at m e nt. 
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 3 9  of 7 5  
A Es r e p ort e d d uri n g t h e p ar e nt st u dy t h at ar e o n g oi n g at t h e e n d of tr e at m e nt visits will c o nti n u e t o 
b e f oll o w e d u p i n t his st u dy u ntil r es ol uti o n or t h e p artici p a nt c o m pl et es t h e st u dy, w hic h e v er is 
first. 
 
T w o s u m m ari es will b e pr o d uc e d f or e ac h cl assific ati o n of a dv ers e ev e nts. O n e will us e D P S 1 a n d 
r e p ort o nl y t h os e a dv ers e e v e nts t h at st art e d d uri n g t his st u dy u ntil 3 0 d a ys aft er t h e l ast d os e of 
I M P a n d o n e t h at will us e D P S 2 a n d  r e p ort t h os e a dv ers e e v e nts t h at occ ur f oll o wi n g t h e first d os e 
of activ e I M P, eit h er i n t h e p ar e nt st u dy or i n t his st u dy u ntil 3 0 d ays aft er t h e l ast d os e of I M P i n t his 
st u dy. 
 
O nly tr e at m e nt e m er g e nt A Es ( T E A Es) will b e i ncl u d e d i n t h e s u m m ari es, pr e -tr e at m e nt A Es will b e 
i ncl u d e d i n t h e listi n gs of all A Es.   
 
All A Es will b e c o d e d usi n g M e d D R A . T h e dicti o n ar y will b e u p d at e d t hr o u g h t h e lif e of t h e st u dy wit h 
v ersi o n  2 4. 0 us e d i niti ally .  S e v erit y of e v e nt will b e c o d e d usi n g t h e C o m m o n T er mi n ol o gy Cr it eri a 
f or A dv ers e E v e nts ( C T C A E) v 5. 0 .  
 
I n a d diti o n t o t h e pri m ar y A E s u m m ary s p ecifi e d i n S ecti o n 9, T E A Es will  b e s u m m ariz e d b y s yst e m 
or g a n cl ass ( S O C) a n d pr ef err e d t er m ( P T)  f or e ac h of t h e r e p orti n g p eri o ds. F or t h e p eri o d  d efi n e d 
by t his st u dy o nl y, t h e n u m b er a n d p erc e nt a g e of p artici p a nts r e p orti n g ev e nts, a n d  t h e n u m b er a n d 
r at e p er 1 0 0 p ati e nt-y e ars of ev e nts  will b e pr es e nt e d. F or t h e  s u m m ary l o oki n g at t h e p eri o d 
d efi n e d si nc e first d os e of acti v e I M P by eit h er i n t his st u dy a n d t h e r el ev a nt p ar e nt st u dy, t h e 
n u m b er a n d p erc e nt a g e of p artici p a nts r e p orti n g ev e nts, a n d t h e n u m b er a n d r at e p er 1 0 0 p ati e nt-
y e ars of ev e nts will b e pr es e nt e d.  
 
F or  t h e i nci d e nc e st atistics, a p artici p a nt w h o h as m ulti pl e e v e nts i n t h e s a m e S O C or t h e s a m e 
pr ef err e d t er m will b e c o u nt e d o nly o nc e . A ll e v e nts will b e c o u nt e d i n t h e n u m b er a n d r at e p er 1 0 0 
y e ars  st atistics. A dv ers e ev e nt s u m m ari es will b e s ort e d b y t h e i nt er n ati o n ally a gr e e d S O C or d er 
(T a bl e 1 0 ) a n d d ecr e asi n g i nci d e nc e of pr ef err e d t er m wit hi n S O C i n t h e t ot al c ol u m n. 
 
R el at e d T E A Es, T E A Es of Gr a d e 3 or a b ov e, s eri o us T E A Es a n d T E A Es l e a di n g t o disc o nti n u ati o n of 
st u dy dr u g will als o b e s u m m aris e d by S O C a n d P T i n t h e m a n n er d escri b e d a b ov e.  
 
N o n -s eri o us T E A Es will b e als o s u m m arize d b y S O C a n d P T, h o w e v er, P Ts will b e pr es e nt e d o nl y i n 
c as e of T E A Es r e p ort e d  by at l e ast 5 % of p artici p a nts i n a n y tr e at m e nt gr o u p. 
 
1 1. 4  D e at hs, S eri o us A d v ers e E v e nts a n d ot h er Si g nific a nt A d v ers e E v e nts  
S eri o us A Es, f at al A Es  a n d  A Es l e a di n g t o disc o nti n u ati o n of st u dy dr u g  will  e ac h  b e list e d s e p ar at el y 
by p artici p a nt.  
 
N o s p ecific a dv ers e ev e nts ar e c o nsi d er e d t o b e of s p eci al i nt er est f or E D P 1 8 1 5.  
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 4 0  of 7 5  
1 1. 5  Pr e g n a nci es  
Pr e g n a nc y t est d at a will b e list e d o nl y.  
 
1 1. 6  Cli nic al L a b or at or y E v al u ati o ns  
C e ntr al l a b or at or y d at a will b e us e d f or all s af e ty l a b or at ory ev al u ati o ns. T a bl e 1 1  s h o ws t h e 
p ar a m et ers w hic h will b e c oll ect e d a n d t h e u nits i n w hic h t h e y will b e s u p pli e d . L a b d at a will b e 
tr a nsf or m e d as a p pr o priat e t o t h e I nt er n ati o n al Syst e m of U nits ( SI u nits) as p art of t h e S D T M 
pr o gr a m mi n g a n d SI u nits will b e us e d f or all s u m m ari es . 
 
H a e m at ol o gy a n d c h e mistry p ar a m et ers will b e s u m m ariz e d b y visit, i ncl u di n g c h a n g e fr o m b as eli n e 
f or all p ost -b as eli n e visits , usi n g D P S3 . 
 
T h e n u m b er a n d p erc e nt a g e of p artici p a nts s h o wi n g s hifts fr o m b as eli n e t o w orst -c as e p ost-b as eli n e 
wit h r es p ect t o t h e n or m al r a n g es will als o b e s u m m ari ze d f or e ac h h a e m at ol o gy a n d c h e mistr y 
p ar a m et er , usi n g D P S1 .  C at e gori es will b e:  
•  
L o w 
•  
N or m al  
•  
Hi g h  
 
H a e m at ol o gy a n d c h e mistry v al u es will als o b e fl a g g e d f or p ot e nti ally cli nic ally i m p ort a nt ( P CI) 
v al u es if t h ey m e et a ny of t h e crit eri a f or Gr a d e 2 or hi g h er e v e nts acc or di n g t o C T C A E V 5. 0. T h e P CI 
crit eri a ar e list e d i n T a bl e 1 1 .  T h e n u m b er a n d p erc e nt a g e of p artici p a nts s h o wi n g s hifts fr o m 
b as eli n e t o w orst -c as e b as eli n e wit h r es p ect t o P CI crit eri a will b e s u m m arize d f or all p ar a m et ers 
w h er e P CI crit eri a h a v e b e e n d efi n e d , usi n g D P S1 . C at e g ori es will b e:  
•  
L o w 
•  
Wit hi n r a n g e  
•  
Hi g h  
 
F or b ot h t h e n or m al r a n g e a n d P CI s u m m ari es, t h e d et er mi n ati o n of w orst -c as e p ost-b as eli n e will 
c o nsi d er b ot h sc h e d ul e d a n d u nsc h e d ul e d ass ess m e nts w hic h occ ur  aft er t h e first d os e of st u dy 
tr e at m e nt.  P erc e nt a g es will us e t h e n u m b er of p artici p a nts wit h at l e ast o n e p ost-b as eli n e 
ass ess m e nt a v ail a bl e as t h e d e n o mi n at or. If t h e b as eli n e v al u e is missi n g it will b e ass u m e d t o b e 
n or m al / wit hi n r a n g e.  W orst-c as e ca n b e eit h er Hi g h or L o w a n d if a p artici p a nt h as p ost -b as eli n e 
v al u es b ot h a b o v e a n d b el o w t h e n or m al r a n g e / P CI crit eri a t h e n t h ey will b e c o u nt e d i n b ot h 
r el ev a nt c at e g ori es. 
 
H a e m at ol o gy a n d c h e mistry d at a will b e list e d, i ncl u di n g c h a n g es fr o m b as eli n e , n or m al r a n g es, fl a gs 
f or m e as ur e m e nts o utsi d e t h e n or m al r a n g e, a n d fl a gs f or m e eti n g P CI crit eri a.  I n a d diti o n, f or 
p artici p a nts w h o m e et at l e ast o n e P CI crit eri a, all v al u es wit hi n t h e l a b or at or y ty p e ( h a e m at ol o gy or 
c h e mistr y) will b e list e d s e p ar atel y.  
 
Uri n al ysis d at a will b e list e d o nl y.   
 




St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 4 2  of 7 5  
p artici p a nts wit h at l e ast o n e p ost -b as eli n e a ss ess m e nt a v ail a bl e. If t h e b as eli n e v al u e is missi n g it 
will b e ass u m e d t o b e wit hi n r a n g e f or t his s u m m ar y.   
 
All vit al si g ns d at a will b e list e d, i ncl u di n g fl a gs f or v al u es w hic h m e et t h e P CI crit eri a. I n a d diti o n, a 
s e p ar at e listi n g of all vit al si g ns ass ess m e nts f or a n y p artici p a nt w h o m e et h as at l e ast o n e v al u e 
m e eti n g t h e P CI crit eri a will b e pr o d uc e d.  
 
1 1. 7. 3  P h ysic al E x a mi n ati o n  
All cli nic all y si g nific a nt a b n or m aliti es i d e ntifi e d t hr o u g h p hysic al ex a mi n ati o n s h o ul d b e  r ec or d e d as 
a dv ers e ev e nts a n d  list e d wit h a d v ers e ev e nts. N o s e p ar at e listi n gs of p hysic al ex a mi n ati o ns will b e 
pr o d uc e d.  
 
1 2  R e p orti n g C o n v e nti o ns  
W h e n r e p orti n g r el ati v e fr e q u e nci es or ot h er p erc e nt a g e v al u es, t h e f oll o wi n g r ul es a p pl y:  
•  
F or v al u es w h er e all s u bj ects f ulfil c ert ai n crit eri a, t h e p erc e nt a g e v al u e will b e dis pl a y e d as 
1 0 0  
•  
F or v al u es w h er e t h e a bs ol ut e fr e q u e ncy is 0, t h er e will b e n o p erc e nt a g e pr es e nt e d at all  
•  
All ot h er p erc e nt a g e dis pl ays will us e 1 d eci m al pl ac e  
 
W h e n r e p orti n g d escri pti v e st atistics, t h e f o ll o wi n g r ul es will a p pl y i n g e n er al: 
•  
n will b e a n i nt e g er  
•  
M e a n a n d m e di a n will us e 1 d eci m al pl ac e m or e t h a n t h e ori gi n al d at a  
•  
St a n d ar d d e vi ati o n will us e 2 d eci m al pl ac es m or e t h a n t h e n ori gi n al d at a  
•  
Mi ni m u m a n d m axi m u m will b e r e p ort e d usi n g t h e s a m e n u m b er of d eci m al pl ac es as t h e 
ori gi n al v al u e  
•  
If n o s u bj ects h av e d at a at a giv e n ti m e p oi nt, f or ex a m pl e, t h e n o nl y n = 0 will b e pr es e nt e d. 
H o w ev er, if n < 3, pr es e nt t h e n, mi n a n d m axi m u m o nly. If n = 3, n, m e a n, m e di a n, mi ni m u m 
a n d m axi m u m will b e pr es e nt e d o n l y. T h e ot h er d escri pti v e st atistics will b e l eft bl a nk 
 
1 3  T ec h nic al D et ails  
St atistic al ev al u ati o n will b e p erf or m e d b y
 
 
T h e d at as ets  f or t h e i nt eri m a n d fi n al a n alys e s will f oll o w a n alysis d at as et m o d el ( A D a M) d at a 
s p ecific ati o ns a n d will us e d st a n d ar d d at a t a b ul ati o n m o d el ( S D T M) d at a s ets pr o vi d e d b y   
d at a 
m a n a g e m e nt as t h e s o urc e d at a . 
 
All a n al ys es will b e p erf or m e d usi n g S A S v ersi o n 9. 4  or hi g h er ( S A S I nstit ut e, C ar y, N C, U S A ). 
 
1 4  S u m m ar y of C h a n g es fr o m t h e Pr ot oc ol 
T h e S A P is b as e d o n t h e l at est Pr ot oc ol v 4 . 0. 










































St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 6 3  of 7 5  
1 7  A p p e n di x 2: Ecz e m a Ar e a a n d S e v erit y I n d e x   
 
I nt e nsit y 
A r e pr es e nt ativ e ar e a of ps ori asis is s el ect e d f or e ac h b o dy r e gi o n ( h e a d a n d n eck, u p p er li m bs, tr u n k, 
l o w er li m bs). 
 
T h e av er a g e s ev erity of e ac h of f o ur si g ns ( er yt h e m a/r e d n ess, e d e m a/ p a p ul ati o n, exc ori ati o n, 
lic h e nific ati o n) i n e ac h b o dy r e gi o n is sc or e d as: 
•  
0 = N o n e  
•  
1 = Mil d  
•  
2  = M o d er at e  
•  
3  = S e v er e  
H alf p oi nts ( 1. 5 a n d 2. 5) m a y b e us e d.  0 . 5 is n ot p er mitt e d –  if a si g n is pr es e nt it s h o ul d b e at l e ast mil d. 
 
A s ev erity sc or e is c alc ul at e d f or e ac h b o dy r e gi o n as t h e s u m of t h e f o ur sc or es f or eryt h e m a /r e d n ess, 
e d e m a/ p a p ul ati o n, exc ori ati o n a n d lic h e nific ati o n . 
•  
A 1  =  A s ev erity sc or e f or h e a d a n d n ec k 
•  
A 2  =  A s ev erity sc or e f or u p p er extr e miti es  
•  
A 3  =  A s ev erity sc or e f or tr u n k 
•  
A 4  =  A s ev erity sc or e f or l o w er extr e miti es  
 
E ac h s u bt ot al is m ulti pli e d  by t h e b o dy s urf ac e ar e a r e pr es e nt e d by t h at r e gi o n as f oll o ws:  
•  
B 1 = 0. 1 x A 1  
•  
B 2 = 0. 2 x A 2  
•  
B 3 = 0. 3 x A 3  
•  
B 4 = 0. 4 x A 4  
 
P erc e nt a g e ar e a aff ect e d   
T h e p erc e nt a g e ar e a aff ect e d b y ps ori asis is ev al u at e d i n e ac h of t h e f o ur b o dy r e gi o ns.  I n e ac h b o dy 
r e gi o n t h e ar e a is ex pr ess e d as: 
•  
0 = n ot aff ect e d at all  
•  
1 = 1 –  9 %  
•  
2 = 1 0 -2 9 %  
•  
3 = 3 0 -4 9 %  
•  
4 = 5 0 % -6 9 %  
•  
5 = 7 0 -8 9 %  
•  
6 = 9 0 -1 0 0 %  
 
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 6 4  of 7 5  
E A SI  sc or e c alc ul ati o n 
E ac h of t h e b o dy ar e a sc or es is m ulti pli e d by t h e s ev erit y sc or e f or t h e r el ev a nt b o dy r e gi o n ( B 1-B 4) t o 
giv e f o ur ar e a i nt e nsity sc or es ( C 1 -C 4).  
 
T h e E A SI  sc or e is t h e s u m of t h e f o ur ar e a i nt e nsit y sc or es: 
  
E A SI  sc or e = C 1 + C 2 + C 3 + C 4. 
 
E A SI sc or e r a n g es fr o m 0 t o 7 2.  
 
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 6 5  of 7 5  
1 8  A p p e n di x 3 : V ali d at e d I n v esti g at or Gl o b al Ass ess m e nt  
T h e  vI G A sc or e is s el ect e d usi n g t h e d escri pt ors b el o w t h at b est d escri b e t h e ov er all a p p e ar a nc e of t h e 
l esi o ns at a giv e n ti m e p oi nt. It is n ot n ec ess ar y t h at all c h ar act eristics u n d er M or p h ol o gic al D escri pti o n 
b e pr es e nt.  
 
•  
0 = Cl e ar  
N o i nfl a m m at ory si g ns of at o pic d er m atitis ( n o er yt h e m a, n o i n d ur ati o n/ p a p ul ati o n, n o 
lic h e nific ati o n, n o o ozi n g/cr usti n g). P ost-i nfl a m m at ory h y p er pi g m e nt ati o n a n d/ or 
hy p o pi g m e nt ati o n m a y b e pr es e nt.  
•  
1 = Al m ost cl e ar  
B ar el y p erc e pti bl e eryt h e m a, b ar el y p erc e pti bl e i n d ur ati o n/ p a p ul at i o n, a n d/ or mi ni m al 
lic h e nific ati o n. N o o ozi n g or cr usti n g. 
•  
2 = Mil d  
Sli g ht b ut d efi nit e er yt h e m a ( pi nk), sli g ht b ut d efi nit e i n d ur ati o n/ p a p ul ati o n, a n d/ or sli g ht b ut 
d efi nit e lic h e nific ati o n. N o o ozi n g or cr usti n g.  
•  
3 = M o d er at e  
Cl e arly p erc e pti bl e eryt h e m a ( d ull r e d), cl e arl y p erc e pti bl e i n d ur ati o n/ p a p ul ati o n, a n d/ or cl e arly 
p erc e pti bl e lic h e nific ati o n. O ozi n g a n d cr usti n g m ay b e pr es e nt.  
•  
4 = S e v er e  
M ar k e d eryt h e m a ( d e e p or bri g ht r e d), m ar k e d i n d ur ati o n/ p a p ul ati o n, a n d/ or m ar k e d 
lic h e nific ati o n. Dis e as e is wi d es pr e a d i n ext e nt. O ozi n g or cr usti n g m a y b e pr es e nt. 
 
T h e  vI G A sc or e r a n g es fr o m 0 t o 4 .  
 
 
 




St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 6 7  of 7 5  
2 0  A p p e n di x 5 : P ati e nt Ori e nt e d Ecz e m a M e as ur e  
T h e P O E M  c o nsists of 7  q u esti o ns:  
1.  Ov er t h e l ast w e ek, o n h o w m a ny d a ys h as y o ur ski n b e e n itc hy b ec a us e of t h e ecz e m a? 
2.  Ov er t h e l ast w e ek, o n h o w m a ny ni g hts h as y o ur sl e e p b e e n dist ur b e d b ec a us e of t h e ecz e m a?  
3.  Ov er t h e l ast w e ek, o n h o w m a ny d a ys h as y o ur ski n b e e n bl e e di n g b ec a us e of t h e ecz e m a?  
4.  Ov er t h e l ast w e ek, o n h o w m a ny d a ys h as y o ur s ki n b e e n w e e pi n g or o ozi n g cl e ar fl ui d b ec a us e 
of t h e ecz e m a?  
5.  Ov er t h e l ast w e ek, o n h o w m a ny d a ys h as y o ur ski n b e e n cr ack e d b ec a us e of t h e ecz e m a ?  
6.  Ov er t h e l ast w e ek, o n h o w m a ny d a ys h as y o ur ski n b e e n fl a ki n g off b ec a us e of t h e ecz e m a?  
7.  Ov er t h e l ast w e ek, o n h o w m a ny d a ys h as y o ur ski n f elt dr y or r o u g h b ec a us e of t h e ecz e m a? 
 
E ac h q u esti o n is sc or e d as:  
•  
0 = N o d ays  
•  
1 = 1 -2 d a ys  
•  
2 = 3 -4 d a ys  
•  
3 = 5 -6 d a ys  
•  
4 = Ev er y d ay  
 
If o n e q u esti o n is l eft u n a ns w er e d t his is sc or e d 0 a n d t h e sc or es ar e s u m m e d a n d ex pr ess e d as us u al 
o ut of a m axi m u m of 2 8.  
If t w o or m or e q u esti o ns ar e l eft u n a ns w er e d t h e q u esti o n n air e is n ot sc or e d. 
 
T h e P O E M  sc or e is t h e s u m of t h e 7  it e m sc or es a n d r a n g es fr o m 0 t o 2 8 . 
 
 
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 6 8  of 7 5  
2 1  A p p e n di x 6 : D er m at ol o g y Q u alit y of Lif e I n d e x 
 
T h e DL QI  c o nsists of 1 0 q u esti o ns: 
 
1.  Ov er t h e l ast w e ek, h o w itc hy, s or e, p ai nf ul or sti n gi n g h as y o ur s ki n b e e n ?  
2.  Ov er t h e l ast w e ek, h o w e m b arr ass e d or s elf-c o nsci o us h a v e y o u b e e n b ec a us e of y o ur ski n ?  
3.  Ov er t h e l ast w e ek, h o w m uc h h as y o ur s ki n i nt erf er e d wit h y o u g oi n g s h o p pi n g or l o oki n g aft er 
y o ur h o m e or g ar d e n?  
4.  Ov er t h e l ast w e ek, h o w m uc h h as y o ur s ki n i nfl u e nc es t h e cl ot h es y o u w e ar?  
5.  Ov er t h e l ast w e ek, h o w m uc h h as y o ur s ki n aff ect e d a ny s oci al or l eis ur e acti viti es ?  
6.  Ov er t h e l ast w e ek, h o w m uc h h as y o ur s ki n m a d e it diffic ult f or y o u t o d o a n y s p ort ?  
7.  Ov er t h e l ast w e ek, h as y o ur s ki n pr ev e nt e d y o u fr o m w orki n g or st u dyi n g ?  
If “ N o”, ov er t h e l ast w e e k h o w m uc h h as y o ur s ki n b e e n a pr o bl e m at w ork or st u dyi n g ? 
8.  Ov er t h e l ast w e ek, h o w m uc h h as y o ur s ki n cr e at e d pr o bl e ms f or y o ur p art n er or a n y of y o ur 
cl os e fri e n ds or r el ati v es ? 
9.  Ov er t h e l ast w e ek, h o w m uc h h as y o ur s ki n c a us e d a ny s ex u al diffic ulti es ?  
1 0.  Ov er t h e l ast w e ek, h o w m uc h of a pr o bl e m h as t h e tr e at m e nt f or y o ur s ki n b e e n, f or ex a m pl e  
by m aki n g y o ur h o m e m essy, or t aki n g u p ti m e ?  
 
Q u esti o ns 1 a n d 2  is sc or e d o n a f o ur-p oi nt Li k ert sc al e:  
•  
3 = V er y m uc h  
•  
2 = A l ot  
•  
1 = A littl e  
•  
0 = N ot at all  
 
Q u esti o ns 3 -6 a n d 8 -1 0 als o h a v e a n o pti o n of n ot r el e v a nt a n d ar e sc or e d as:  
•  
3 = V er y m uc h  
•  
2 = A  l ot 
•  
1 = A littl e  
•  
0 = N ot at all  
•  
0 = N ot r el ev a nt  
 
Q u esti o n 7 is a 2 -p art q u esti o n a n d is sc or e d as:  
•  
3 = Y es  
•  
2 = N o; A l ot  
•  
1 = N o; A littl e  
•  
0 = N o; N ot at all  
•  
0 = N ot r el ev a nt  
A ny u n a ns w er e d q u esti o n is sc or e d as 0.  


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 6 9  of 7 5  
T h e DL QI sc or e is t h e s u m of t h e 1 0 it e m sc or es. 
 


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 7 0  of 7 5  
2 2  A p p e n di x 9 : At o pic D er m atitis C o ntr ol T o ol  
 
T h e A D C T  c o nsists of 6  q u esti o ns:  
1.  Ov er t h e l ast w e ek, h o w w o ul d y o u r at e y o ur ecz e m a -r el at e d sy m pt o ms (f or ex a m pl e, itc hi n g, 
dr y s ki n, ski n r as h)?  
2.  Ov er t h e l ast w e ek, h o w m a ny d a ys di d y o u h a v e i nt e ns e e pis o d es of itc hi n g b ec a us e of y o ur 
ecz e m a ?  
3.  Ov er t h e l ast w e ek, h o w b ot h er e d h av e y o u b e e n by y o ur ecz e m a?  
4.  Ov er t h e l ast w e ek, h o w m a ny ni g hts di d y o u h av e tr o u bl e f alli n g or st a yi n g asl e e p b ec a us e of 
y o ur ecz e m a ?  
5.  Ov er t h e l ast w e ek, h o w m uc h di d y o ur ecz e m a aff ect y o ur d ail y acti viti es ?  
6.  Ov er t h e l ast w e ek, h o w m uc h di d y o ur ecz e m a aff ect y o ur m o o d or e m oti o ns ?  
 
Q u esti o ns 1 is sc or e d as : 
•  
0 = N o n e  
•  
1  = Mil d  
•  
2  = M o d er at e  
•  
3  = S e v er e  
•  
4 = V er y s ev er e  
 
Q u esti o n  2  is sc or e d as: 
•  
3 = N ot at all  
•  
2 = 1 -2 d a ys  
•  
1 = 3 -4 d a ys  
•  
0 = 5 -6 d a ys  
•  
0 = E v er y d ay  
 
Q u esti o n 3  is sc or e d as: 
•  
0 = N ot at all  
•  
1  = A littl e  
•  
2  = M o d er at el y  
•  
3  = V er y  
•  
4 = Extr e m el y  
 
Q u esti o n  4  ar e sc or e d as:  
•  
3 = N o ni g hts  
•  
2 = 1 -2 ni g hts  
•  
1 = 3 -4 ni g hts  
•  
0 = 5 -6 ni g hts  


St atistic al A n alysis Pl a n   
V ersi o n 2. 0 , 0 7-J U N-2 0 2 3  
 
E D P 1 8 1 5 -2 0 8  
 
 
  
 
P a g e 7 1  of 7 5  
•  
0 = E v er y ni g ht  
 
Q u esti o n s 5  a n d 6 ar e  sc or e d as: 
•  
0 = N ot at all  
•  
1  = A littl e  
•  
2  = M o d er at el y  
•  
3  = A l ot  
•  
4 = Extr e m el y  
 
T h e A D C T t ot al sc or e  is t h e s u m of t h e 6  A D C T q u esti o ns a n d r a n g es fr o m 0 t o 2 4.