Clinical trial NCT03667014
Conditions: Atopic Dermatitis Atopic Dermatitis Eczema
Keywords: atopic dermatitis eczema dupilumab
Sponsor: University of California, San Francisco
Start date: 2018-11-01; Completion date: 2022-12-15
Enrollment: 34 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a single-arm, open-label study, which will examine the effect of dupilumab on quality of life in atopic dermatitis patients.

Detailed description:
This is a single center, open-label study, which will examine the effect of dupilumab on quality of life in atopic dermatitis (AD). Thirty patients with moderate to severe AD will receive dupilumab for a treatment period of 52 weeks (i.e. last injection on week 48). Improvement in patient quality of life after 52 weeks of treatment with dupilumab will be evaluated using validated dermatologic and non-dermatologic psychometric instruments. The primary endpoint is the improvement in quality of life measured by change in Psychological General Well-Being scale (PGWB) at Week 16 from baseline. Additionally, patients will be given a video recording device to document their experience with the study drug at home. Video footage of patient experiences will be compiled at the end of the study. The compiled video footage will subsequently be watched and analyzed to further understand the experiences of atopic dermatitis patients, and how undergoing dupilumab treatment alters these patients' experiences and attitudes with their skin disease.

Arms: arm 1: 30 subjects will receive dupilumab for a treatment period of 52 weeks. All patients quality of life measures will be assessed with Psychological General Well-Being scale (PGWB), Work Productivity and Activity Impairment scale (WPAI), and Dermatology Life Quality Index (DLQI). Symptom and satisfaction will be assessed with Treatment Satisfaction Questionnaire for Medication (TSQM), Itch Numerical Rating Scale, Pain Numerical Rating Scale, and Pittsburgh Sleep Quality Assessment (PSQI).
Interventions: intervention 1: Dupilumab
Intervention descriptions: intervention 1: Dupilumab treatment

Protocol documents:
Prot_SAP_000.pdf: 
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Clinical Research Protocol
The impact of dupilumab on quality of life in moderate to severe atopic dermatitis patients
Protocol Number:
R668-AD-1833
Version Date:
February 14, 2019
Investigational Product:
Dupilumab 
Sponsor:
Tina Bhutani, MD
Principal Investigator:
Tina Bhutani, MD
515 Spruce Street
San Francisco, CA 94118
Telephone: (415) 476-4701
Fax: (415) 502-4126
E-mail: tina.bhutani@ucsf.edu
Funding Organization:
Regeneron Pharmaceuticals and Sanofi
Approval:
PI or Sponsor Signature (Name and Title) 
Date
This confidential information about an investigational product is provided for the exclusive use of 
investigators of this product and is subject to recall at any time.  The information in this document 
may not be disclosed unless federal or state law or regulations require such disclosure.  Subject to the 
foregoing, this information may be disclosed only to those persons involved in the study who have a 
need to know, with the obligation not to further disseminate this information.  
NCT 03667014


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PROTOCOL AGREEMENT
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include ensuring the safety of the study subjects enrolled under my supervision and providing 
Regeneron with complete and timely information, as outlined in the protocol.  It is understood 
that all information pertaining to the study will be held strictly confidential and that this 
confidentiality requirement applies to all study staff at this site. Furthermore, on behalf of the 
study staff and myself, I agree to maintain the procedures required to carry out the study in 
accordance with accepted GCP principles and to abide by the terms of this protocol.
Protocol Number:  R668-AD-1833
Protocol Title: The impact of dupilumab on quality of life in moderate to severe atopic dermatitis 
patients
Protocol Date:  February 14, 2019
Investigator Signature 
Date
Print Name and Title
Site Name
Address
Phone Number


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Contents
1
BACKGROUND.........................................................................................................................................9
2
STUDY RATIONALE ................................................................................................................................9
3
STUDY OBJECTIVES .............................................................................................................................10
3.1
PRIMARY OBJECTIVE ..................................................................................................................................10
3.2
SECONDARY OBJECTIVES ...........................................................................................................................10
4
STUDY DESIGN.......................................................................................................................................11
4.1
STUDY OVERVIEW......................................................................................................................................11
5
CRITERIA FOR EVALUATION.............................................................................................................11
5.1
PRIMARY ANALYSIS ENDPOINT ..................................................................................................................11
5.2
SECONDARY ANALYSIS ENDPOINTS............................................................................................................11
5.3
SAFETY EVALUATIONS ...............................................................................................................................11
6
SUBJECT SELECTION...........................................................................................................................12
6.1
STUDY POPULATION ...................................................................................................................................12
6.2
INCLUSION CRITERIA..................................................................................................................................12
6.3
EXCLUSION CRITERIA.................................................................................................................................12
7
CONCURRENT MEDICATIONS ...........................................................................................................13
7.1
ALLOWED MEDICATIONS AND TREATMENTS..............................................................................................13
7.2
PROHIBITED MEDICATIONS AND TREATMENTS...........................................................................................13
8
STUDY TREATMENTS...........................................................................................................................13
8.1
SUPPLY OF STUDY DRUG AT THE SITE ........................................................................................................13
8.2
STORAGE ....................................................................................................................................................13
8.3
DOSAGE/DOSAGE REGIMEN........................................................................................................................13
8.4
ADMINISTRATION INSTRUCTIONS ...............................................................................................................13
8.5
STUDY DRUG ACCOUNTABILITY.................................................................................................................14
8.6
MEASURES OF TREATMENT COMPLIANCE ..................................................................................................14
9
STUDY PROCEDURES AND GUIDELINES..........................................................................................14
9.1
CLINICAL ASSESSMENTS.............................................................................................................................14
9.1.01
Medical History.................................................................................................................................14
9.1.02
Concomitant Medications..................................................................................................................14
9.1.03
Demographics ...................................................................................................................................15
9.1.04
Physical Examination........................................................................................................................15
9.1.05
Vital Signs .........................................................................................................................................15
9.1.08
Quality of life measures.....................................................................................................................15
9.1.09
Symptom and satisfaction measures..................................................................................................15
9.1.10
Photography......................................................................................................................................16
9.1.11
Video recording.................................................................................................................................16
9.1
CLINICAL LABORATORY MEASUREMENTS..................................................................................................16
9.2.01
Hematology .......................................................................................................................................16


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9.2.02
Blood Chemistry Profile....................................................................................................................16
9.2.03
Pregnancy Test..................................................................................................................................16
10
EVALUATIONS BY VISIT......................................................................................................................17
10.01
VISIT 1 (SCREENING)..............................................................................................................................17
10.02
VISIT 2 (WEEK 0) ...................................................................................................................................17
10.03
VISIT 3 (WEEK 4) ...................................................................................................................................18
10.04
VISIT 4 (WEEK 8) ...................................................................................................................................19
10.05
VISIT 5 (WEEK 12) .................................................................................................................................19
10.06
VISIT 6 (WEEK 16) .................................................................................................................................20
10.07
VISIT 7 (WEEK 20) .................................................................................................................................21
10.08
VISIT 8 (WEEK 24) .................................................................................................................................21
10.09
VISIT 9 (WEEK 28) .................................................................................................................................22
10.10
VISIT 10 (WEEK 32) ...............................................................................................................................23
10.11
VISIT 11 (WEEK 36) ...............................................................................................................................24
10.12
VISIT 12 (WEEK 40) ...............................................................................................................................24
10.13
VISIT 13 (WEEK 44) ...............................................................................................................................25
10.14
VISIT 14 (WEEK 48) ...............................................................................................................................26
10.15
VISIT 15 (WEEK 52) ...............................................................................................................................26
10.16
EARLY TERMINATION.............................................................................................................................27
11
ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION...................................................28
11.1
ADVERSE EVENTS.......................................................................................................................................28
11.2
SERIOUS ADVERSE EXPERIENCES (SAE) ....................................................................................................29
11.3.
SERIOUS ADVERSE EXPERIENCE REPORTING..............................................................................................30
12
DISCONTINUATION AND REPLACEMENT OF SUBJECTS .............................................................31
12.1
EARLY DISCONTINUATION OF STUDY DRUG...............................................................................................31
12.2
WITHDRAWAL OF SUBJECTS FROM THE STUDY...........................................................................................31
13
PROTOCOL VIOLATIONS ....................................................................................................................32
14
STATISTICAL METHODS AND CONSIDERATIONS .........................................................................32
14.1
ANALYSIS OF PRIMARY ENDPOINT .............................................................................................................32
14.2
ANALYSIS OF SECONDARY ENDPOINTS.......................................................................................................33
14.3
SAMPLE SIZE ..............................................................................................................................................33
15
DATA COLLECTION, RETENTION AND MONITORING .................................................................33
15.1
DATA COLLECTION INSTRUMENTS .............................................................................................................33
15.2
 DATA MANAGEMENT PROCEDURES...........................................................................................................34
15.4
ARCHIVAL OF DATA ...................................................................................................................................34
16
ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS..............................................35
16.1
PROTOCOL AMENDMENTS ..........................................................................................................................35
16.2
INSTITUTIONAL REVIEW BOARDS AND INDEPENDENT ETHICS COMMITTEES..............................................35
16.3
INFORMED CONSENT FORM ........................................................................................................................36
16.4
PUBLICATIONS............................................................................................................................................36
16.5
INVESTIGATOR RESPONSIBILITIES...............................................................................................................37


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17
REFERENCES .........................................................................................................................................37
APPENDIX 1.  EVALUATION SCHEDULE...................................................................................................39


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LIST OF ABBREVIATIONS
AD
Atopic dermatitis
AE
Adverse event
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
BSA
Body surface area
BUN
Blood urea nitrogen
CBC
CFR
Complete blood count
Code of Federal Regulations
CRF
Case Report Form
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Committee
DSMB
Data Safety Monitoring Board
EASI
Eczema area severity score
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GGT
Gamma-glutamyl transferase
HIPAA
Health Insurance Portability and Accountability Act of 1996
ICF
Informed consent form
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IGA
Investigator Global Assessment
IRB
IUD
Institutional Review Board
Intrauterine device
PGWB
Psychological General Well-Being scale
PI
Principal Investigator
PK
QoL
Pharmacokinetic
Quality of life
SAE
Serious adverse experience
WPAI 
Work Productivity and Activity Impairment scale


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PROTOCOL SYNOPSIS
TITLE
The impact of dupilumab on quality of life in moderate to severe atopic 
dermatitis patients
SPONSOR
Tina Bhutani, MD
FUNDING
Regeneron Pharmaceuticals and Sanofi
STUDY DESIGN 
& OVERVIEW
This is an open-label study which will examine the effect of dupilumab on 
quality of life in a real-world setting
PRIMARY 
OBJECTIVE
To evaluate the improvement in patient quality of life after 52 weeks of 
treatment with dupilumab using validated dermatologic and non-
dermatologic psychometric instruments. The primary endpoint is the 
improvement in quality of life measured by change in Psychological 
General Well-Being scale (PGWB) at Week 16 from baseline.
SECONDARY 
OBJECTIVES
To evaluate physical parameters and patient reported symptoms and 
satisfaction with treatment after 52 weeks of dupilumab using validated 
dermatologic and non-dermatologic instruments.
NUMBER OF 
SUBJECTS
Up to 30 patients will be enrolled
SUBJECT 
SELECTION 
CRITERIA
Inclusion Criteria:
1.
Ability to provide written informed consent and comply with the 
protocol
2.
At least 18 years of age
3.
Diagnosis of atopic dermatitis at least 6 months prior to enrollment, 
having stable (unchanged) disease for at least 2 months
4.
Non-immune-compromised status
5.
Subjects have moderate-to-severe atopic dermatitis, classified as 
Eczema Area and Severity Index (EASI) score greater than or equal 
to 6
6.
Subject is considered a candidate for phototherapy or systemic 
therapy
7.
Subjects of child-bearing potential must have a negative urine 
pregnancy test within 7 days prior to first dose of dupilumab
8.
Sexually active subjects of childbearing potential must agree to use 
medically acceptable form of contraception during screening and 
throughout the study
9.
Subject meets concomitant medication requirements (see below)
Exclusion Criteria:


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1.
Younger than 18 years of age
2.
Has mild atopic dermatitis, classified as EASI score less than 6
3.
History of known or suspected intolerance to any of the ingredients 
of the investigational study product
4.
Evidence of skin conditions other than atopic dermatitis that would 
interfere with study-related evaluations of atopic dermatitis.
5.
History of immune-compromised status [e.g. human 
immunodeficiency virus (HIV) positive status or other immune 
suppressing drug] or a congenital or acquired immunodeficiency
6.
Has a poorly controlled medical condition including, but not 
limited to, unstable cardiovascular disease, poorly controlled 
diabetes, recent stroke, history of recurrent infections, or any other 
condition for which, in the opinion of the investigator, participation 
in the study would place the subject at risk
7.
Has a history of or ongoing drug or alcohol abuse
8.
Is not willing to comply with concomitant medication requirements
9.
Is known, or suspected of being unable to comply with the study 
protocol
10.
Subjects who are well controlled on current treatment for atopic 
dermatitis and participation in the study may worsen disease 
control significantly
11.
Subjects who have been previously treated and/or are currently on 
dupilumab will not be eligible to participate. 
STUDY 
TREATMENT
Dupilumab (Dupixent ®) 600 mg SC at week 0, then 300 mg SC every 
other week.
STUDY 
DURATION
The total duration of the study is expected to be 104 weeks: 52 weeks for 
recruitment and 52 weeks for site visits.
PRIMARY 
ENDPOINT
Improvement in quality of life measured by change in Psychological 
General Well-Being scale (PGWB) at Week 16 from baseline. 
SECONDARY 
ENDPOINT
1.
Improvement in work productivity measured by change in Work 
Productivity and Activity Impairment scale (WPAI) at Week 16 
from baseline
2.
Improvement in quality of life measured by change in 
Dermatology Life Quality Index (DLQI) at Week 16 from baseline
3.
Efficacy of drug as measured by EASI and IGA at week 16 from 
baseline
4.
Safety of drug
5.
Improvement in itch and pain scores using numerical rating scales 
at Week 16 from baseline
6.
Improvement in sleep quality measured by the Pittsburgh Sleep 
Quality Assessment (PSQI) at Week 16 from baseline


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7.
Evaluation of subjective video documentation
SAFETY 
EVALUATIONS
Safety will be evaluated by tabulation of adverse events (AEs), including 
any Serious Adverse Events (SAEs) within treatment groups.  All AEs 
occurring during the study will be recorded.  Descriptions of adverse 
events will include the date of onset, the date the adverse event ended, the 
severity of the adverse event, and the outcome.  All reported adverse 
events will be summarized by the number of subjects reporting adverse 
events, body system, severity, seriousness, and relationship to study 
treatment.
STATISTICS
Primary Analysis 
Plan
The primary endpoint is improvement of PGWB at week 16 compared to 
baseline. Statistical significance will be based on resulting p-values of 0.05 
or less.  Last observation carried forward (LOCF) will be used to impute 
missing data.  Analyses will be conducted on an intent-to-treat (ITT) 
population (all subjects enrolled and receiving the treatments).  Analyses 
on the per-protocol (PP) population will be considered supportive of the 
ITT analyses.  Subjects will be eligible for the PP analyses if they complete 
the 52 week evaluation without any noteworthy study protocol violations 
(i.e. failure to use the study medications or investigator activity that could 
have possibly interfered with the therapeutic administration of the 
treatment or the precise evaluation of treatment efficacy).
ETHICAL 
CONSIDER-
ATIONS
This study will be conducted in accordance with applicable laws and 
regulations and according to the recommendations of International 
Conference on Harmonization Good Clinical Practice (ICH GCP) 
guidelines and those of the Declaration of Helsinki (Edinburgh, 2000); 
only after approval for the study has been obtained from the relevant 
regulatory authority and relevant independent ethics committee (IEC). The 
institutional review board (IRB)/IEC must review and approve the protocol 
and informed consent form (ICF) before any subjects are enrolled. The 
subject must be consented using the approved ICF before any procedures 
specified in the protocol are performed.


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1
BACKGROUND
Atopic dermatitis (AD) is a common, complex, immune-mediated condition affecting 5-15% of 
children and adults worldwide. Adults with AD suffer from severe pruritus and inflammatory 
skin rash with a chronic disease course.
Patients with moderate-to-severe AD report a multidimensional burden including itch, pain, 
sleep disturbance, anxiety and depression, and impaired health-related quality-of-life (HRQoL). 
Patients suffering from AD are more likely to be depressed when compared to the general 
population, which can lead to increased suicidal ideation. Furthermore, AD can create a negative 
impact in the workplace, as patients with the disease are more likely to miss work due to their 
skin symptoms. With the significant negative psychosocial impact of AD, patients not only want 
to improve their skin lesions, but also their personal experience with this chronic disease.
2
STUDY RATIONALE
The overall aim of this study is to demonstrate, beyond the Dermatology Life Quality Index 
(DLQI), improvement in the quality of life of adults with moderate-to-severe AD who are being 
treated with dupilumab for 1 year. 
The University of California, San Francisco (UCSF) Skin Treatment Center is a high-volume 
atopic dermatitis referral center whose activities include outpatient care, a phototherapy unit, a 
Goeckerman tar treatment program, and over 20 clinical trials conducted over the past three 
years. 
The Skin Treatment Center has conducted several similar studies in the treatment of moderate to 
severe plaque psoriasis, a disease which has taken more than 10 years to be seen as a respectable 
condition on par with other serious medical diagnoses.  In the process of making psoriasis 
worthy of reimbursement from payers, the government, and even in the eyes of the general 
public, some key data attesting quantitatively the negative impact of the disease, played a very 
important role. Having been involved in this process, and learning from the psoriasis experience, 
our aim is to make atopic dermatitis as respectable as psoriasis, without spending upwards of 10 
years to get to that point. The most critical data that can help AD attain this respected status is 
the quantitative documentation regarding the negative impact of the disease on patients that is 
comparable to other serious disorders. This cannot be done with the DLQI or any other skin 
specific instruments. 
We have specifically chosen the Psychological General Well Being Index (PGWB) and Work 
Productivity and Activity Index (WPAI) as quality of life assessment tools because they are not 
specific to skin diseases; they have been used extensively for non-dermatologic serious medical 
conditions. By deliberately using validated QOL instruments applicable broadly to serious 
medical conditions, we hope to show that patients being considered for treatment have baseline 
deficiencies in psychological well-being and work productivity comparable to patients with 


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serious non-dermatological disorders (such has heart disease, cancer, and untreated diabetes). 
Moreover, we aim to go beyond this by involving a therapeutic intervention to hopefully show 
that treatment with dupilumab not only significantly improves these parameters, but also brings 
them to a level comparable to a disease-free non-patient population. 
Beyond administering these questionnaires, we will also take a novel approach to assessing 
patient experience with a medication. Each patient will be given a video recording device to 
document their experience from a pre-dupilumab state to a post-dupilumab state in the privacy of 
their own home. Human-interest stories excite payers and the general public who are not 
healthcare providers. It is best to have both human-interest stories in a narrative form before and 
after treatment as well as quantitative documentation with the PGWB and WPAI. 
It is hoped that the information gained from this study will not only provide more insight into the 
psychosocial and occupational impact of AD, but also confirm the value of dermatological care 
by demonstrating and documenting how an effective treatment modality like dupilumab can 
reverse these negative impacts. 
Thus, in this real-world study of atopic dermatitis, we aim to examine the value and efficacy of 
medical intervention, extending beyond physical improvement, and into the realm of 
psychosocial and occupational functions. 
3
STUDY OBJECTIVES
3.1
Primary Objective
To evaluate the improvement in patient quality of life after 52 weeks of treatment with 
dupilumab using validated dermatologic and non-dermatologic psychometric instruments. The 
primary endpoint is the improvement in quality of life measured by change in Psychological 
General Well-Being scale (PGWB) at Week 16 from baseline.
3.2
Secondary Objectives
To evaluate physical parameters and patient reported symptoms and satisfaction with treatment 
after 52 weeks of dupilumab using validated dermatologic and non-dermatologic instruments.
4
STUDY DESIGN
4.1
Study Overview
This is a single-center study. Up to thirty subjects with moderate to severe atopic dermatitis will 
receive dupilumab for a treatment period of 52 weeks. Patients will be evaluated using validated 
dermatologic and non-dermatologic psychometric instruments throughout the study period to 
measure quality of life, as well as satisfaction and symptom measures. Additionally, patients will 


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record their experience with the study drug at home during the study period. See Appendix 1 for 
a timeline of study activities.
5
CRITERIA FOR EVALUATION
5.1
Primary Analysis Endpoint
Improvement in quality of life measured by change in Psychological General Well-Being scale 
(PGWB) at Week 16 from baseline.
5.2
Secondary Analysis Endpoints
1. Improvement in work productivity measured by change in Work Productivity and 
Activity Impairment scale (WPAI) at Week 16 from baseline
2. Improvement in quality of life measured by change in Dermatology Life Quality Index 
(DLQI) at Week 16 from baseline
3. Efficacy of drug as measured by EASI and IGA at week 16 from baseline
4. Safety of drug
5. Improvement in itch and pain scores using numerical rating scales at Week 16 from 
baseline
6. Improvement in sleep quality measured by the Pittsburgh Sleep Quality Assessment 
(PSQI) at Week 16 from baseline
7. Evaluation of subjective video documentation
5.3
Safety Evaluations
Safety and tolerability to dupilumab will be assessed by adverse events, vital signs, physical 
examinations (including skin examinations and injection-site evaluations), and concomitant 
medication review. Laboratory assessments will be performed at screening.
6
SUBJECT SELECTION
6.1
Study Population
Subjects will be selected from qualified volunteers at least 18 years of age, with stable 
(unchanged for 2 months), moderate to severe atopic dermatitis who are candidates for 
phototherapy or systemic therapy.
6.2
Inclusion Criteria
1. Ability to provide written informed consent and comply with the protocol
2. At least 18 years of age
3. Diagnosis of atopic dermatitis at least 6 months prior to enrollment, having stable 
(unchanged) disease for at least 2 months


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4. Non-immune-compromised status
5. Subjects have moderate-to-severe atopic dermatitis, classified as Eczema Area and 
Severity Index (EASI) score greater than or equal to 6
6. Subject is considered a candidate for phototherapy or systemic therapy
7. Subjects of child-bearing potential must have a negative urine pregnancy test within 7 
days prior to first dose of dupilumab
8. Sexually active subjects of childbearing potential must agree to use medically acceptable 
form of contraception during screening and throughout the study
9. Subject meets concomitant medication requirements as documented below
6.3
Exclusion Criteria
1. Younger than 18 years of age
2. Has mild atopic dermatitis, classified as EASI score less than 6
3. History of known or suspected intolerance to any of the ingredients of the investigational 
study product
4. Evidence of skin conditions other than atopic dermatitis that would interfere with study-
related evaluations of atopic dermatitis
5. History of immune-compromised status [e.g. human immunodeficiency virus (HIV) 
positive status or other immune suppressing drug] or a congenital or acquired 
immunodeficiency 
6. Has a poorly controlled medical condition including, but not limited to, unstable 
cardiovascular disease, poorly controlled diabetes, recent stroke, history of recurrent 
infections, or any other condition for which, in the opinion of the investigator, 
participation in the study would place the subject at risk
7. Has a history of or ongoing drug or alcohol abuse
8. Is not willing to comply with concomitant medication requirements
9. Is known, or suspected of being unable to comply with the study protocol
10. Subjects who are well controlled on current treatment for atopic dermatitis and 
participation in the study may worsen disease control significantly
11. Subjects who have been previously treated and/or are currently on dupilumab will not be 
eligible to participate. 
7
CONCURRENT MEDICATIONS
7.1
Allowed Medications and Treatments
As this is a real-world trial, during the course of the study, subjects may continue treatment with 
topical steroids, phototherapy, or other systemic agents as deemed appropriate by the study 
investigators. 
Any medications that the subject receives during the study must be recorded. Vaccines 
administered to the subject should be listed as a concomitant medication. 


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7.2
Prohibited Medications and Treatments
During the study period, concurrent use of other biologic medications apart from the study 
medication is prohibited. No new treatments should be added during the study period that the 
patient was not using consistently prior to study onset.
8
STUDY TREATMENTS  
8.1
Supply of Study Drug at the Site
Regeneron will ship the study drug to the investigational sites. The study drug is supplied in 
cartons containing either two 300 mg/2 mL solution pre-filled syringes with needle shield or 2 
pre-filled syringes. Each kit of study drug will be labeled with the required FDA warning 
statement, the protocol number, and directions for use and storage.
8.2
Storage
Dupilumab must be refrigerated at 36°F to 46°F (2°C to 8°C) in the original carton to protect 
from light. The medication will be kept in a temperature-monitored refrigerator at the study site. 
If necessary, pre-filled syringes may be kept at room temperature up to 77°F (25°C) for a 
maximum of 14 days. The product will be kept in the original carton until the time of use.
8.3
Dosage/Dosage Regimen
Dupilumab will be administered at an initial dose of 600 mg subcutaneously followed by 300 mg 
subcutaneously through the study, which is the FDA-approved and recommended dose for 
dupilumab. There is no weight-based dosing. The dosing schedule will be as follows: dupilumab 
600mg subcutaneously once at week 0, followed by dupilumab 300 mg subcutaneously every 
other week until week 50. 
8.4
Administration Instructions 
Doses of study treatment will be administered at the study site after the study assessments for the 
visit have been completed, at visits occurring between weeks 0 and 48. Subjects will administer 
the medication independently every other week only after they have demonstrated the 
competency to self-administer the treatment outside of the study site. Patients not demonstrating 
competency to self-administer the treatment will be administered the medication at the study site 
as needed. There will be no study medication given after week 50 of the study. 
The subject should be instructed to contact the investigator if he/she is unable for any reason to 
attend a study visit as scheduled. All dates and times of injections done to the subject during the 
study must be recorded on the Dosage Administration Record CRF. The investigator will 
promote compliance by instructing the subject to attend the study visits as scheduled and by 
stating that compliance is necessary for the subject’s safety and the validity of the study.


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8.5
Study Drug Accountability
The qualified site personnel will maintain an accurate record of the shipment and dispensing of 
study treatment in a treatment accountability log. All study treatment kits assigned to the subject 
during the study will be recorded. 
8.6
Measures of Treatment Compliance
Subjects will be given scheduled doses of dupilumab at each visit from visit 2 (week 0) until visit 
14 (week 48). Subjects will be given a dosing diary at every visit between weeks 0 and 48 to 
record their scheduled injections administered at home every other week.
9
STUDY PROCEDURES AND GUIDELINES
A Schedule of Events representing the required testing procedures to be performed for the 
duration of the study is diagrammed in Appendix 1.
Prior to conducting any study-related activities, written informed consent and the Health 
Insurance Portability and Accountability Act (HIPAA) authorization must be signed and dated 
by the subject.
All clinical assessments will take place at the study site at 515 Spruce St., San Francisco, CA 
94118.
All blood draws will take place at UCSF Blood Draw Lab at Mount Zion at 2330 Post St., First 
Floor, San Francisco, CA 94115.
9.1
Clinical Assessments
9.1.01
Medical History 
Relevant medical history, including history of current disease and previous atopic dermatitis 
treatment, and information regarding underlying diseases will be recorded at Screening.
9.1.02
Concomitant Medications
All concomitant medication and concurrent therapies will be documented at Screening, at every 
site visit, and at early termination when applicable.  Dose, route, unit frequency of 
administration, indication for administration, and dates of medication will be captured.
9.1.03
Demographics 
Demographic information (date of birth, age, gender, ethnicity) will be recorded at Screening.
9.1.04
Physical Examination
A complete physical examination will be performed by either the investigator or a sub-
investigator who is a physician at Screening. New abnormal physical exam findings must be 
documented and will be followed by a physician or other qualified staff at the next scheduled 
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9.1.05
Vital Signs
Body temperature, blood pressure, pulse, and respirations will be performed after resting for 
5 minutes at all site visits. Height and weight will additionally be measured at each study visit.
9.1.06 Adverse Events
Information regarding occurrence of adverse events will be captured at weeks 4, 8, 12, 16, 20, 
24, 28, 32, 36, 40, 44, 48, 52, and at early termination when applicable. Duration (start and stop 
dates and times), severity/grade, outcome, treatment and relation to study drug will be recorded 
on the case report form (CRF).
9.1.07 EASI and IGA
Eczema Area and Severity Index (EASI) and Investigator Global Assessment (IGA) will be 
completed at Screening and weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early 
termination when applicable.
9.1.08
Quality of life measures
Quality of life measures will be assessed at weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 
52, and at early termination when applicable. 
Quality of life measures will be assessed using the following validated instruments: 
1) Psychological General Well-Being scale (PGWB)
2) Work Productivity and Activity Impairment scale (WPAI)
3) Dermatology Life Quality Index (DLQI)
9.1.09
Symptom and satisfaction measures
Symptom and satisfaction measures will be assessed at weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 
40, 44, 48, 52, and at early termination when applicable. 
Symptom and satisfaction measures will be assessed using the following validated instruments:
1) Itch Numerical Rating Scale
2) Pain Numerical Rating Scale
3) Pittsburgh Sleep Quality Assessment (PSQI)
9.1.10
Photography
Photographs (full front and back, excluding the face) will be taken at weeks 0, 16, 24, 52, and at 
early termination when applicable.
9.1.11
Video recording
Patients will be given a video recording device at week 0, and will be instructed on how to use it 
to record video. Patients will be instructed to record videos of themselves at home discussing 
their experience with the study drug and its impact on their skin and quality of life for roughly 5-
10 minutes/week. The patient will be the only person in the video (i.e. there will be no family 
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record in a private setting (i.e. alone in their bedroom or office) and similarly, will be instructed 
to keep the recording device and its stored footage in a private location. Patients will be given a 
list of topics at the week 0 visit to be used as guidelines for discussion:
1) Please discuss any changes you have observed in your skin while using the study drug.
2) What is the most important change that you have experienced while using the study drug?
3) What are your goals with undergoing this medication for the future?
4) Please discuss how these changes in your skin have impacted both your life (day-to-day 
behaviors such as clothing choice or activities) and the lives of your loved ones.
5) Please discuss any changes in how you feel since starting the study medication (mood, 
sleep, work, home life, personal relationships).
6) Please discuss your overall experience using the study drug.
7) Please discuss any interesting or notable experiences or events that have occurred to you 
while using the study drug.
8) Please feel free to discuss anything else pertaining to your experience with eczema
Patients will be instructed to bring in their video recording devices to their study visits at weeks 
4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early termination when applicable. At these 
visits, study staff will download the patient videos to a secure local storage site.
9.1 Clinical Laboratory Measurements
9.2.01
Hematology
Blood will be obtained and sent to the clinical hematology lab for a complete blood count 
(hemoglobin, hematocrit, red blood cell count, white blood cell count, white blood cell 
differential, and platelet count) for determination of systemic evidence for infection and/or 
inflammation at Screening.
9.2.02
Blood Chemistry Profile
Blood will be obtained and sent to the clinical chemistry lab for determination of electrolyte 
levels, serum BUN, creatinine, AST, ALT, and alkaline phosphatase at Screening.
9.2.03
Pregnancy Test
A urine pregnancy test will be obtained at the study site for female subjects of childbearing 
potential at Screening and weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early 
termination when applicable.
10
EVALUATIONS BY VISIT
See Appendix 1 for Evaluation Schedule.
10.01 Visit 1 (Screening)
1. Verify that patient meets all inclusion criteria and exclusion criteria
2. Informed Consent/HIPAA Authorization/UCSF Experimental Subject’s Bill of Rights - 
Prior to any testing under this protocol, including screening and evaluations, written 


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informed consent will be obtained from the subject by the investigators.  The background 
of the proposed study, benefits, and risks of procedures will be explained to the subject.  
Informed consent will be obtained after the subject has a chance to ask questions.  A copy 
of the signed and dated informed consent, HIPAA Authorization, and UCSF 
Experimental Subject’s Bill of Rights will be given to the subject.  At the time of written 
informed consent, subjects will be given the name and phone number of personnel at the 
study site that can be called in the event of an emergency or to report any medical 
symptoms or untoward medical occurrence that is of concern to the subject.  
3. Obtain patient demographic information
4. Medical history – a full medical history including all medications
5. Atopic dermatitis treatment history – past treatments with special focus on any treatment 
during the last 30 days
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Comprehensive physical exam
d. Eczema Area and Severity Index (EASI) 
e.
Investigator’s Global Assessment (IGA)
7. Clinical Laboratories:
a.
Hematology
b. Chemistry
8. Urine Pregnancy Test (if applicable)
10.02 Visit 2 (Week 0)
1. Review inclusion and exclusion criteria
2. Brief interim medical history
3. Review concomitant medications
4. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
5. Urine pregnancy test (if applicable)
6. Full-body photography (excluding face)
7. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI


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8. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
9. Study drug injection
10. Dispense study medication and dosing diaries for home use
11. Sign out video recording device and instruct patients on proper use
10.03 Visit 3 (Week 4)
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications
4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI
9. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
10. Study drug injection
11. Dispense study drug and dosing diary for home use
10.04
Visit 4 (Week 8)
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications


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4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI
9. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
10. Study drug injection
11. Dispense study drug and dosing diary for home use
10.05 Visit 5 (Week 12) 
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications
4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI


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9. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
10. Study drug injection
11. Dispense study drug and dosing diary for home use
10.06 Visit 6 (Week 16) 
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications
4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Full-body photography (excluding face) 
9. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI
10. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
11. Study drug injection
12. Dispense study drug and dosing diary for home use
10.07 Visit 7 (Week 20) 
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications


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4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI
9. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
10. Study drug injection
11. Dispense study drug and dosing diary for home use
10.08 Visit 8 (Week 24) 
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications
4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Full-body photography (excluding face)
9. Quality of Life Measures: 
a.
WPAI
b. PGWB


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c.
DLQI
10. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
11. Study drug injection
12. Dispense study drug and dosing diary for home use
10.09 Visit 9 (Week 28) 
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications
4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI
9. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
10. Study drug injection
11. Dispense study drug and dosing diary for home use
10.10 Visit 10 (Week 32) 
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications


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4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI
9. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
10. Study drug injection
11. Dispense study drug and dosing diary for home use
10.11 Visit 11 (Week 36) 
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications
4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI


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9. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
10. Study drug injection
11. Dispense study drug and dosing diary for home use
10.12
Visit 12 (Week 40) 
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications
4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI
9. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
10. Study drug injection
11. Dispense study drug and dosing diary for home use
10.13 Visit 13 (Week 44) 
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications
4. Study staff download patient videos


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5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI
9. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
10. Study drug injection
11. Dispense study drug and dosing diary for home use
10.14 Visit 14 (Week 48) 
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications
4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI
9. Other patient questionnaires: 


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a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
10. Study drug injection
11. Dispense study drug and dosing diary for home use
10.15 Visit 15 (Week 52) 
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications
4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration
6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Full-body photography (excluding face) 
9. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI
10. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
10.16 Early termination
1. Brief interim medical history
2. Review adverse events
3. Reconcile concomitant medications
4. Study staff download patient videos
5. Study staff collect, review, and record home study drugs administration


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6. Physical examination
a.
Height and weight
b. Vital signs: temperature, blood pressure, pulse, and respiratory rate
c.
Eczema Area and Severity Index (EASI) 
d. Investigator’s Global Assessment (IGA)
7. Urine pregnancy test (if applicable)
8. Full-body photography (excluding face) 
9. Quality of Life Measures: 
a.
WPAI
b. PGWB
c.
DLQI
10. Other patient questionnaires: 
a.
Itch Numerical Rating Scale 
b. Pain Numerical Rating Scale 
c.
Pittsburgh Sleep Quality Assessment (PSQI)
11 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION
11.1 Adverse Events
Definition of an AE: Any untoward medical occurrence in a subject administered a 
pharmaceutical product that does not necessarily have a causal relationship with the treatment. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal (investigational) 
product, whether or not considered related to the investigational medicinal product.
Investigational Medicinal Product (IMP) includes the drug under evaluation and the comparator 
drug(s) if specified as part of the research objective, given at any time during the study. Medical 
conditions/diseases present before starting the drug of interest are only considered adverse events 
if they worsen after starting the drug of interest.
The occurrence of adverse events will be sought by non-directive questioning of the patient at 
each visit during the study. Adverse events also may be detected when they are volunteered by 
the patient during or between visits or through physical examination, laboratory test, or other 
assessments. All adverse events will be recorded in the study database including the following 
information:
1. the severity grade (mild, moderate, severe)
2. its relationship to the drug(s) of interest (suspected/not suspected)
3. its duration (start and end dates or if continuing at final exam)
4. whether it constitutes a serious adverse event (SAE)


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AE Severity
The National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) 
Version 3.0 should be used to assess and grade AE severity, including laboratory abnormalities 
judged to be clinically significant. The modified criteria can be found in the study manual.  If the 
experience is not covered in the modified criteria, the guidelines shown in Error! Reference 
source not found. below should be used to grade severity.  It should be pointed out that the term 
“severe” is a measure of intensity and that a severe AE is not necessarily serious.
Table 1.  AE Severity Grading
Severity (Toxicity Grade)
Description
Mild (1)
Transient or mild discomfort; no limitation in activity; no medical 
intervention or therapy required. The subject may be aware of the sign 
or symptom but tolerates it reasonably well.
Moderate (2)
Mild to moderate limitation in activity, no or minimal medical 
intervention/therapy required.
Severe (3)
Marked limitation in activity, medical intervention/therapy required, 
hospitalizations possible.
Life-threatening (4)
The subject is at risk of death due to the adverse experience as it 
occurred. This does not refer to an experience that hypothetically 
might have caused death if it were more severe.
Table 2.  AE Relationship to Study Drug
Relationship
to Drug
Comment
Definitely
Previously known toxicity of agent; or an event that follows a reasonable temporal 
sequence from administration of the drug; that follows a known or expected response 
pattern to the suspected drug; that is confirmed by stopping or reducing the dosage of 
the drug; and that is not explained by any other reasonable hypothesis.
Probably
An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to the suspected drug; that is 
confirmed by stopping or reducing the dosage of the drug; and that is unlikely to be 
explained by the known characteristics of the subject’s clinical state or by other 
interventions.
Possibly
An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to that suspected drug; but 
that could readily have been produced by a number of other factors.


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Unrelated
An event that can be determined with certainty to have no relationship to the study 
drug.
11.2
Serious Adverse Experiences (SAE)
A SAE is any untoward medical occurrence that at any dose:
 
results in death,

is life-threatening,

requires inpatient hospitalization or prolongation of existing hospitalization,

results in persistent or significant disability/incapacity,

is a congenital anomaly/birth defect, 

is otherwise a significant medical event.
This includes any SAEs likely to arise from the trial indication or progression of 
underlying/concomitant illness(es) (e.g. progression of cancer in oncology trials), unless 
specified in the protocol as study specific exemptions.
Any SAE, irrespective of causality, occurring after the subject has provided informed consent 
and until four weeks after the subject has stopped study participation must be reported unless 
otherwise stated in the protocol. SAEs occurring after four weeks from ending study 
participation should only be reported if considered by the Investigator attributable to the 
exposure to the investigational drug(s) during the trial period. This includes the period in which 
the study protocol interferes with the standard medical treatment given to a subject, even if study 
treatment has not yet started (e.g. withdrawal of previous treatment during washout period, 
change in treatment to a fixed dose of concomitant medication).
11.3.
Serious Adverse Experience Reporting
Study sites will document all SAEs that occur (whether or not related to study drug) per UCSF 
CHR Guidelines.  The collection period for all SAEs will begin after informed consent is 
obtained and end after procedures for the final study visit have been completed.
SAEs occurring after four weeks from ending study participation should only be reported if 
considered by the Investigator attributable to the exposure to the investigational drug(s) during 
the trial period. This includes the period in which the study protocol interferes with the standard 
medical treatment given to a subject, even if study treatment has not yet started (e.g. withdrawal 
of previous treatment during washout period, change in treatment to a fixed dose of concomitant 
medication).
In accordance with the standard operating procedures and policies of the local Institutional 
Review Board (IRB)/Independent Ethics Committee (IEC), the site investigator will report SAEs 
to the IRB/IEC.  


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Timelines: All serious adverse events (SAEs) must be reported by the sites to Sponsor within 24 
hours of occurrence of the SAE. The timelines for investigator initiated trials reporting to 
Regeneron Pharmaceuticals will be done as per Third Party Study/Investigator Initiated Trial 
Agreement.  All reports must be sent to Regeneron as below:

Fax SAE/CIOMS or MedWatch Reports to 914-345-7476

Email forms to medical.safety@regeneron.com
Follow-up reports: SAEs will be followed until resolution or until it is judged to be permanent, 
and an assessment will be made at each visit (or more frequently, if necessary) of any changes in 
severity, the suspected relationship to the drug of interest, the interventions required to treat it, 
and the outcome. 
The Sponsor shall support Regeneron in the following-up of all SAEs so that complete 
information is available to maintain patient safety and also as part of any commitments by 
Regeneron to any Health authority OR specific Health authority follow-up requests for the 
product under investigation.
Pregnancies: Any occurrences of a pregnancy in a patient (or a patients partner) during study 
participation will be collected. All pregnancies will be followed up to determine outcome, 
including spontaneous or voluntary termination, details of the birth, and the presence or absence 
of any birth defects, congenital abnormalities, or maternal and/or newborn complications.
12 DISCONTINUATION AND REPLACEMENT OF SUBJECTS
12.1 Early Discontinuation of Study Drug 
A subject may be discontinued from study treatment at any time if the subject, the investigator, 
or the Sponsor feels that it is not in the subject’s best interest to continue.  The following is a list 
of possible reasons for study treatment discontinuation: 

Subject withdrawal of consent (or assent)

Subject is not compliant with study procedures

Adverse event that in the opinion of the investigator would be in the best interest of the 
subject to discontinue study treatment

Protocol violation requiring discontinuation of study treatment

Lost to follow-up

Sponsor request for early termination of study

Positive pregnancy test (females)
If a subject is withdrawn from treatment due to an adverse event, the subject will be followed 
and treated by the Investigator until the abnormal parameter or symptom has resolved or 
stabilized.  
All subjects who discontinue study treatment should come in for an early discontinuation visit as 


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soon as possible and then should be encouraged to complete all remaining scheduled visits and 
procedures.
All subjects are free to withdraw from participation at any time, for any reason, specified or 
unspecified, and without prejudice.
Reasonable attempts will be made by the investigator to provide a reason for subject 
withdrawals.  The reason for the subject’s withdrawal from the study will be specified in the 
subject’s source documents Refer to Section 10.13 for early termination procedures.
12.2
Withdrawal of Subjects from the Study
A subject may be withdrawn from the study at any time if the subject, the investigator, or the 
Sponsor feels that it is not in the subject’s best interest to continue.  
All subjects are free to withdraw from participation at any time, for any reason, specified or 
unspecified, and without prejudice.
Reasonable attempts will be made by the investigator to provide a reason for subject 
withdrawals.  The reason for the subject’s withdrawal from the study will be specified in the 
subject’s source documents. As noted above, subjects who discontinue study treatment early (i.e., 
they withdraw prior to Visit 11) should have an early discontinuation visit. Refer to Section 
10.13 for early termination procedures. Subjects who withdraw after Visit 1 but prior to Visit 10 
should be encouraged to come in for a final visit (and the procedures to be followed would 
include those for their next scheduled visit). Subjects who sign the informed consent form (ICF) 
and who are discontinued or withdraw from the study before study product administration will be 
defined as screen failures. No data will be collected in the CRFs for screen failure subjects.
13 PROTOCOL VIOLATIONS
A protocol violation occurs when the subject, investigator, or Sponsor fails to adhere to 
significant protocol requirements affecting the inclusion, exclusion, subject safety and primary 
endpoint criteria.  Protocol violations for this study include, but are not limited to, the following:

Failure to meet inclusion/exclusion criteria.

Use of a prohibited concomitant medication.

Non-compliance with study drug regimen.

Non-compliance with study visit procedures.

Failure to comply with Good Clinical Practice (GCP) guidelines will also result in a 
protocol violation. The PI will determine if a protocol violation will result in withdrawal 
of a subject.
When a protocol violation occurs, it will be discussed with the investigator and a Protocol 
Violation Form detailing the violation will be generated. This form will be signed by a Sponsor 
representative and the Investigator. A copy of the form will be filed in the site’s regulatory 


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binder and in the Sponsor’s files.
14 STATISTICAL METHODS AND CONSIDERATIONS
Prior to the analysis of the final study data, a detailed Statistical Analysis Plan (SAP) will be 
written describing all analyses that will be performed.  The SAP will contain any modifications 
to the analysis plan described below.  
14.1 Analysis of Primary Endpoint
The primary endpoint is improvement of PGWB at week 16 compared to baseline. Statistical 
significance will be based on resulting p-values of 0.05 or less.  Last observation carried forward 
(LOCF) will be used to impute missing data.  Analyses will be conducted on an intent-to-treat 
(ITT) population (all subjects enrolled and receiving the treatments).  Analyses on the per-
protocol (PP) population will be considered supportive of the ITT analyses.  Subjects will be 
eligible for the PP analyses if they complete the 52 week evaluation without any noteworthy 
study protocol violations (i.e. failure to use the study medications or investigator activity that 
could have possibly interfered with the therapeutic administration of the treatment or the precise 
evaluation of treatment efficacy).
14.2
 Analysis of Secondary Endpoints
1. Efficacy Endpoints
a. EASI and IGA scores at week 16 will be compared to baseline.
2. Safety Endpoints
a. Safety will be evaluated by tabulation of adverse events (AEs), including any 
Serious Adverse Events (SAEs) within treatment groups.  All AEs occurring 
during the study will be recorded.  Descriptions of adverse events will include the 
date of onset, the date the adverse event ended, the severity of the adverse event, 
and the outcome.  All reported adverse events will be summarized by the number 
of subjects reporting adverse events, body system, severity, seriousness, and 
relationship to study treatment.
3. Analysis of Other Endpoints
a. Other variables may be analyzed and presented descriptively.  The methods to be 
used will include (but are not limited to) parametric and nonparametric analysis, 
means, standard deviations, frequency counts and graphs, as appropriate.
b. Video footage of patient experiences will be compiled at the end of the study. The 
compiled video footage will subsequently be watched and analyzed to further 
understand the experiences of atopic dermatitis patients, and how undergoing 
dupilumab treatment alters these patients’ experiences and attitudes with their 
skin disease. 


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14.3 Sample Size
Up to 30 subjects will receive dupilumab for a treatment period of 52 weeks (i.e. last injection on 
week 50). This is based on previous similar studies investigating the impact of adalimumab and 
ustekinumab on QoL in psoriasis patients which included 33 and 36 patients, respectively.
15 DATA COLLECTION, RETENTION AND MONITORING
15.1
Data Collection Instruments
The Investigator will prepare and maintain adequate and accurate source documents designed to 
record all observations and other pertinent data for each subject. Study personnel at each site will 
enter data from source documents corresponding to a subject’s visit into the protocol-specific 
electronic (eCRF) or paper Case Report Form  when the information corresponding to that visit 
is available. Patient recorded videos will be downloaded to a secure storage site. Subjects will 
not be identified by name in the study database or on any study documents, but will be identified 
by a site number, subject number and initials.
If a correction is required for an eCRF, the time and date stamps track the person entering or 
updating eCRF data and creates an electronic audit trail. If a correction is made on a paper CRF, 
the study staff member will line through the incorrect data, write in the correct data and initial 
and date the change.
The Investigator is responsible for all information collected on subjects enrolled in this study.  
All data collected during the course of this study must be reviewed and verified for completeness 
and accuracy by the Investigator. A copy of the CRF will remain at the Investigator’s site at the 
completion of the study.
15.2
Data Management Procedures
The data will be entered into a validated database.  The Data Management group will be 
responsible for data processing, in accordance with procedural documentation.  Database lock 
will occur once quality assurance procedures have been completed.
All procedures for the handling and analysis of data will be conducted using good computing 
practices meeting FDA guidelines for the handling and analysis of data for clinical trials.
15.3
Data Quality Control and Reporting
After data have been entered into the study database, a system of computerized data validation 
checks will be implemented and applied to the database on a regular basis. On eCRFs, queries 
are entered, tracked, and resolved through the EDC system directly. On paper, query reports 
(Data Clarification Requests) pertaining to data omissions and discrepancies will be forwarded to 
the Investigators and study monitors for resolution.  The study database will be updated in 
accordance with the resolved queries.  All changes to the study database will be documented.
15.4
Archival of Data
The database is safeguarded against unauthorized access by established security procedures; 


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appropriate backup copies of the database and related software files will be maintained. 
Databases are backed up by the database administrator in conjunction with any updates or 
changes to the database.  
At critical junctures of the protocol (e.g., production of interim reports and final reports), data for 
analysis is locked and cleaned per established procedures.
15.5
Availability and Retention of Investigational Records
The Investigator must make study data accessible to the monitor, other authorized 
representatives of the Sponsor (or designee), IRB/IEC, and Regulatory Agency (e.g., FDA) 
inspectors upon request. A file for each subject must be maintained that includes the signed 
Informed Consent, HIPAA Authorization and Assent Form and copies of all source 
documentation related to that subject. The Investigator must ensure the reliability and availability 
of source documents from which the information on the CRF was derived.
All study documents (patient files, signed informed consent forms, copies of CRFs, Study File 
Notebook, etc.) must be kept secured for a period of two years following marketing of the 
investigational product or for two years after centers have been notified that the IND has been 
discontinued. There may be other circumstances for which the Sponsor is required to maintain 
study records and, therefore, the Sponsor should be contacted prior to removing study records for 
any reason.
15.6
Subject Confidentiality
In order to maintain subject confidentiality, only a site number, subject number and subject 
initials will identify all study subjects on CRFs and other documentation submitted to the 
Sponsor.  Additional subject confidentiality issues (if applicable) are covered in the Clinical 
Study Agreement.
16 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS
The study will be conducted according to the Declaration of Helsinki, Protection of Human 
Volunteers (21 CFR 50), Institutional Review Boards (21 CFR 56), and Obligations of Clinical 
Investigators (21 CFR 312).
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other records 
will be identified by a coded number and initials only. All study records will be kept in a locked 
file cabinet and code sheets linking a patient’s name to a patient identification number will be 
stored separately in another locked file cabinet.  Clinical information will not be released without 
written permission of the subject, except as necessary for monitoring by the FDA.  The 
Investigator must also comply with all applicable privacy regulations (e.g., Health Insurance 
Portability and Accountability Act of 1996, EU Data Protection Directive 95/46/EC).
16.1
Protocol Amendments
Any amendment to the protocol will be written by the PI or a sub-investigator with the PI’s 


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approval. Protocol amendments cannot be implemented without prior written IRB/IEC approval 
except as necessary to eliminate immediate safety hazards to patients.  A protocol amendment 
intended to eliminate an apparent immediate hazard to patients may be implemented 
immediately, provided the IRBs are notified within five working days.
16.2
Institutional Review Boards and Independent Ethics Committees
The protocol and consent form will be reviewed and approved by the IRB/IEC of each 
participating center prior to study initiation.  Serious adverse experiences regardless of causality 
will be reported to the IRB/IEC in accordance with the standard operating procedures and 
policies of the IRB/IEC, and the Investigator will keep the IRB/IEC informed as to the progress 
of the study.  The Investigator will obtain assurance of IRB/IEC compliance with regulations.
Any documents that the IRB/IEC may need to fulfill its responsibilities (such as protocol, 
protocol amendments, Investigator’s Brochure, consent forms, information concerning patient 
recruitment, payment or compensation procedures, or other pertinent information) will be 
submitted to the IRB/IEC.  The IRB/IECs written unconditional approval of the study protocol 
and the informed consent form will be in the possession of the Investigator before the study is 
initiated.  The IRB/IECs unconditional approval statement will be transmitted by the Investigator 
to the designee prior to the shipment of study supplies to the site.  This approval must refer to the 
study by exact protocol title and number and should identify the documents reviewed and the 
date of review.
Protocol and/or informed consent modifications or changes may not be initiated without prior 
written IRB/IEC approval except when necessary to eliminate immediate hazards to the patients 
or when the change(s) involves only logistical or administrative aspects of the study.  Such 
modifications will be submitted to the IRB/IEC and written verification that the modification 
was submitted and subsequently approved should be obtained.  
The IRB/IEC must be informed of revisions to other documents originally submitted for review; 
serious and/or unexpected adverse experiences occurring during the study in accordance with the 
standard operating procedures and policies of the IRB; new information that may affect 
adversely the safety of the patients of the conduct of the study; an annual update and/or request 
for re-approval; and when the study has been completed.
16.3
Informed Consent Form 
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH GCP, US 
Code of Federal Regulations for Protection of Human Subjects (21 CFR 50.25[a,b], CFR 50.27, 
and CFR Part 56, Subpart A), the Health Insurance Portability and Accountability Act (HIPAA, 
if applicable), and local regulations.
The Investigator will prepare the informed consent form, assent and HIPAA authorization and 
provide the documents to the Sponsor or designee for approval prior to submission to the 
IRB/IEC.  The consent form generated by the Investigator must be acceptable to the Sponsor and 
be approved by the IRB/IEC.  The written consent document will embody the elements of 
informed consent as described in the International Conference on Harmonization and will also 
comply with local regulations. The Investigator will send an IRB/IEC-approved copy of the 


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Informed Consent Form to the Sponsor (or designee) for the study file.
A properly executed, written, informed consent will be obtained from each subject prior to 
entering the subject into the trial.  Information should be given in both oral and written form and 
subjects (or their legal representatives) must be given ample opportunity to inquire about details 
of the study.  If appropriate and required by the local IRB/IEC, assent from the subject will also 
be obtained.  If a subject is unable to sign the informed consent form (ICF) and the HIPAA 
authorization, a legal representative may sign for the subject.   A copy of the signed consent form 
(and assent) will be given to the subject or legal representative of the subject and the original will 
be maintained with the subject’s records.
16.4
Publications 
The preparation and submittal for publication of manuscripts containing the study results shall be 
in accordance with a process determined by mutual written agreement among the study Sponsor 
and participating institutions.  The publication or presentation of any study results shall comply 
with all applicable privacy laws, including, but not limited to, the Health Insurance Portability 
and Accountability Act of 1996. 
16.5
Investigator Responsibilities
By signing the Agreement of Investigator form, the Investigator agrees to:
1.
Conduct the study in accordance with the protocol and only make changes after notifying 
the Sponsor (or designee), except when to protect the safety, rights or welfare of subjects.
2.
Personally conduct or supervise the study (or investigation).
3.
Ensure that the requirements relating to obtaining informed consent and IRB review and 
approval meet federal guidelines, as stated in § 21 CFR, parts 50 and 56.
4.
Report to the Sponsor or designee any AEs that occur in the course of the study, in 
accordance with §21 CFR 312.64.
5.
Ensure that all associates, colleagues and employees assisting in the conduct of the study are 
informed about their obligations in meeting the above commitments.
6.
Maintain adequate and accurate records in accordance with §21 CFR 312.62 and to make 
those records available for inspection with the Sponsor (or designee).
7.
Ensure that an IRB that complies with the requirements of §21 CFR part 56 will be 
responsible for initial and continuing review and approval of the clinical study.
8.
Promptly report to the IRB and the Sponsor (or designee) all changes in the research activity 
and all unanticipated problems involving risks to subjects or others (to include amendments 
and IND safety reports).
9.
Seek IRB approval before any changes are made in the research study, except when 
necessary to eliminate hazards to the patients/subjects.
10. Comply with all other requirements regarding the obligations of clinical investigators and all 
other pertinent requirements listed in § 21 CFR part 312.


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17
REFERENCES
Abrouk M, Nakamura M, Zhu TH, Farahnik B, Koo J, Bhutani T. The impact of PASI 75 and 
PASI 90 on quality of life in moderate to severe psoriasis patients. J Dermatolog Treat. 2017 Jan 
18: 1-7.
Drucker AM, Wang AR, Qureshi AA. Research gaps in quality of life and economic burden of 
atopic dermatitis: the National Eczema Association burden of disease audit. JAMA 
Dermatology. 2016;152(8):873–4.
Nicholas MN, Gooderham MJ. Atopic Dermatitis, Depression, and Suicidality. J Cutan Med 
Surg. 2017 Jan 1 (Epub Ahead of Print).
Sidbury, R. & Khorsand, K. Evolving Concepts in Atopic Dermatitis. Curr Allergy Asthma 
Rep (2017) 17: 42.
Simpson, E.L. Dupilumab Improves General Health-Related Quality-of-Life in Patients with 
Moderate-to-Severe Atopic Dermatitis: Pooled Results from Two Randomized, Controlled 
Phase 3 Clinical Trials. Dermatol Ther (Heidelb) (2017) 7: 243.


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APPENDIX 1.  EVALUATION SCHEDULE 
Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Time of Visit
Screening
Wk 
0
Wk 
4
Wk 
8
Wk 
12
Wk 
16
Wk 
20
Wk 
24
Wk 
28
Wk 
32
Wk 
36
Wk 
40
Wk 
44
Wk 
48
Wk 
52
Inclusion/Exclusion criteria
X
X
Informed consent
X
Obtain patient demographic information
X
Review full medical and treatment history
X
Review interim medical history
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Review concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examination
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory assessments*
X
Urine pregnancy test
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
EASI and IGA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Quality of life measures**
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Other patient questionnaires***
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Full-body photography (excluding face)
X
X
X
X
Instruct on proper video recording
X
Collect and download patient videos
X
X
X
X
X
X
X
X
X
X
X
X
X
Collect, review, and record home study drug admin
X
X
X
X
X
X
X
X
X
X
X
X
X
On-site study drug administration
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense study meds + dosing diaries for home use
X
X
X
X
X
X
X
X
X
X
X
X
X
* CBC with differential, CMP
** WPAI, PGWB, DLQI
*** Itch Numerical Rating Scale, Pain Numerical Rating Scale, PSQI