The Effects of Dupilumab on Allergic Contact Dermatitis
Phase: PHASE4
Conditions: Allergic Contact Dermatitis
Sponsor: Brigham and Women's Hospital

The Effects of Dupilumab on Allergic Contact Dermatitis 
Protocol Version 13 | 5 October 2023 
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The Effects of Dupilumab on Allergic Contact Dermatitis 
Ari M. Goldminz, MD 
Rachael Clark, MD PhD 
Elizabeth Buzney, MD 
Department of Dermatology 
Brigham and Women’s Hospital 
221 Longwood Ave 
Boston, MA 02115 
617-732-4918 
Protocol Version 13 
5 October 2023 

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TABLE OF CONTENTS 
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TABLE OF CONTENTS .................................................................... 2
PROTOCOL SYNOPSIS ................................................................... 5
1
INTRODUCTION ........................................................................ 10
1.1
Background on Allergic Contact Dermatitis ........................ 10
1.2
Role of T cells in Allergic Contact Dermatitis and 
Dupiluma .......................................................................... 10
1.3
Summary of Results of Investigational Program ................. 11
1.3.1
Pharmacology of Dupilumab ............................................................... 11
1.3.2
Human Pharmacokinetics of Dupilumab ............................................ 11
1.3.3
Clinical Safety with Dupilumab SC Formulation ................................ 12
1.3.3.1
Drug-Related Adverse Events ........................................................... 13
1.4
Research Hypothesis ............................................................ 13
1.5
Study Rationale ...................................................................... 13
2
STUDY OBJECTIVES ................................................................ 14
2.1
Primary Objective .................................................................. 14
2.2
Secondary Objectives ........................................................... 14
3
ETHICAL CONSIDERATIONS ................................................... 15
3.1
Good Clinical Practice ........................................................... 15
3.2
Institutional Review Board/Independent Ethics 
Committee ....................................................................... 15
3.3
Informed Consent .................................................................. 15
4
INVESTIGATIONAL PLAN ........................................................ 16
4.1
Study Design and Duration ................................................... 16
4.2
Study Population ................................................................... 18
4.2.1
Inclusion Criteria ................................................................................... 18

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4.2.2
Discontinuation of Subjects from Treatment ..................................... 19
5
TREATMENTS ........................................................................... 20
5.1
Study Treatment: Dupilumab ................................................ 20
5.1.1
Identification .......................................................................................... 20
5.1.2
Packaging and Labeling ....................................................................... 20
5.1.3
Handling and Dispensing ..................................................................... 20
5.2
Drug Ordering and Accountability........................................ 21
5.2.1
Initial Orders .......................................................................................... 21
5.2.2
Re-Supply .............................................................................................. 21
5.3
Timing of Dose for Each Subject .......................................... 21
5.3.1
Dose Modifications ............................................................................... 21
5.4
Blinding/Unblinding ............................................................... 21
5.5
Concomitant Treatments ....................................................... 21
5.6
Treatment Compliance .......................................................... 21
6
STUDY ASSESSMENTS AND PROCEDURES ......................... 21
6.1
Time and Events Schedule ................................................... 21
*In addition to the allergen patch site and normal skin, an 
additional biopsy will be done on an area of persistent 
dermatitis if present ........................................................... 22
6.2 Study Materials ...................................................................... 22
6.3 Safety Assessments .............................................................. 22 
6.3.1 Physical Examinations ..........................................................................22 
6.4 Efficacy Assessments ........................................................... 23 
6.4.1 Primary Efficacy Assessment .............................................................. 23
6.4.2 Secondary Efficacy Assessments ....................................................... 23 
7 ADVERSE EVENT REPORTING ............................................... 25 
7.1
Adverse Events ...................................................................... 25
7.1.1
Serious Adverse Events ....................................................................... 25
7.1.2
Non-serious Adverse Events ............................................................... 25

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7.1.3
Assignment of Adverse Event Intensity and Relationship to 
Dupilumab ........................................................................................ 25
7.2
Collection and Reporting ...................................................... 26
7.2.1
Serious Adverse Event Collecting and Reporting.............................. 26
7.2.2
Non-Serious Adverse Events (NSAEs) Collecting and 
Reporting ......................................................................................... 26
7.3
Pregnancy .............................................................................. 26
8
DATA MONITORING COMMITTEE ........................................... 26
9
STATISTICAL CONSIDERATIONS ........................................... 26
9.1
Sample Size Determination ................................................... 26
9.2
Populations for Analyses ...................................................... 27
9.3
Endpoint Definitions .............................................................. 27
9.4
Analyses ................................................................................. 28
9.4.1
Demographics and Baseline Characteristics ..................................... 28
9.4.2
Safety Analyses .................................................................................... 28
9.4.3
Efficacy Analyses ................................................................................. 28
10
STUDY MANAGEMENT ........................................................... 29
10.1
Compliance with the Protocol ............................................. 29
10.1.1
Compliance with the Protocol and Protocol Revisions ................... 29
10.2
Records Retention ............................................................... 30
10.2.1
Records Retention .............................................................................. 29
10.2.2
Study Drug Records ........................................................................... 29
11
LIST OF ABBREVIATIONS ..................................................... 30
12
REFERENCES ......................................................................... 31

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PROTOCOL SYNOPSIS 
Protocol Title: 
The Effects of Dupilumab on Allergic Contact Dermatitis 
Site Numbers & Names: 
001 Brigham and Women’s Hospital, Department of 
Dermatology 
Research Hypothesis: 
Dupilumab will most likely benefit patients who have persistent 
allergic contact dermatitis to allergens that primarily elicit a Th2 
immune response (ie rubber and fragrance) but may also benefit 
patients who have sensitivities to allergens that primarily elicit 
Th1, Th17 and Th22 immune responses (ie nickel).
Study Schema: 
Drugs / Doses / 
Length of Treatment)
Dupilumab 300 mg/2mL; 7 doses; 10 weeks of treatment 
Study Objectives: 

Primary: 

Secondary: 
 
Primary endpoint 1: Number of patients who achieve a 
reduction in patch test site reactions from 2+-3+ at 
baseline to "?" or no reaction at week 12. 
 
Secondary endpoint 1: Number of patients who achieve 
a reduction in investigator global assessment (IGA; IGA 
= vIGA-AD) from 3 or greater at screen and baseline to 
0 or 1 at Week 6 and at Week 12.  
 
Secondary endpoint 2a: To quantify the inflammatory 
markers (Th1, Th2, Th17, Th22 immune pathways) in 
the blood and skin of patients before and after 
dupilumab. Secondary endpoint 2b: Changes in IGA 
from baseline to week 12. Other secondary endpoints: 
Change in baseline eczema-area-and-severity-index 
(EASI), body surface area (BSA), numerical rating scale 
(NRS) itch, dermatology life quality index (DLQI), and 
SLEEPYQ from baseline to Week 6 and Week 12.  
 
Secondary endpoint 3: Changes in IGA from baseline to 
Week 6 and to Week 12. 
 
Secondary endpoint 4: To identify and quantify the top T 
cell clones by T-cell receptor high-throughput 
sequencing in the skin and blood before therapy and 
quantify their abundance after therapy. 
 
Other secondary endpoints: Change in baseline 
eczema-area-and-severity- index (EASI), body surface 
area (BSA), numerical rating scale (NRS) itch, 
dermatology life quality index (DLQI), and SLEEPYQ 
from baseline to Week 6 and to 12.  

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Study Design: 
We will recruit 30 patients with allergic contact dermatitis 18 years 
of age and older up to 18 months after patch testing with a 
documented IGA of at least 3 at baseline and screening visits, and 
at least one 2+ (strong) or 3+ (extreme) reaction on patch testing 
to participate in this open-label pilot study.  If more than one 2+ 
(strong) or 3+ (extreme) reactions are present, up to two may be 
selected for evaluation in the study. Priority will be given to nickel, 
fragrance mix I or II, and rubber as these allergens have been 
studied previously with respect to their preferential T helper cell 
skewing. At the initial screening visit, demographic information will 
be obtained, inclusion and exclusion criteria as detailed in Section 
4.2 will be reviewed, and informed consent obtained for those 
deemed eligible for enrollment. A single subcutaneous dose of 
600 mg will be self-administered at week 0 +72-120 hours and 
300 mg every 2 weeks thereafter for a total 10 weeks of therapy.  
Subjects will be evaluated for improvement in primary and 
secondary 
endpoints 
using 
clinical 
examination 
and 
questionnaires during initial and follow-up visits at Week 0, Week 
6, and Week 12 as per Time and Events Schedule below.  Patch 
test site reactions will also be evaluated 72 hours after the Week 
0 and Week 12 visits. Skin biopsies will be taken at these two time 
points from both the patch test site reaction and from normal skin 
taken from a non-dermatitic area on the contralateral side of the 
body. For the Week 12 patch placement, a site contralateral to the 
Week 0 patch placement site will be chosen. If an area of 
persistent dermatitis other than the patch test site(s) is also 
present at week 12+72-120 hours an additional biopsy will be 
taken unless in an anatomic location not amenable to biopsy 
(face, hands, elbows, knees, genitals, feet). Serum samples will 
be obtained at four time-points including Week 0 (prior to patch 
placement), Week 0 +72-120 hours, Week 12 (prior to patch 
placement), and Week 12 +72-120 hours. If subjects do not mount 
a 2+ (strong) or 3+ extreme reaction to the tested allergens at the 
Week 0 +72 hour visit they will be discontinued from the study and 
will not receive dupilumab. These patients will be considered 
screen fails. Week 10 +72-120 hours will conclude the end of the 
treatment portion of the study. Week 12 +72-120 hours will 
conclude the subjects’ participation in the study.  
Accrual Goal: 
(Total number of subjects)
30 subjects 
Accrual Rate: 
(Number of subjects 
expected per month)
1 subject/month
FPFV: 
LPFV: 
Follow Up: 
(dd-mm-yy) 
FPFV: 09-01-18; LPFV: 05-01-20; Follow Up: 3 months after FV 

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Correlative Studies: 
(PK/PD, etc.)
Inclusion Criteria: 
1.  At least 18 years of age 
2. At least one contact allergen with a 2+ (strong) or 3+ (extreme 
reaction) confirmed by patch testing within 18 months of 
the baseline visit that can be duplicated at the initiation 
of the study (placement at Week 0 and patch test 
reaction read at Week 0 +72-120 hours). 
3.  Allergic contact dermatitis diagnosed clinically by the principle 
investigators who have expertise in allergic contact 
dermatitis  
4.  Investigator’s global assessment score of at least 3 (range 0-
4) at the screening and baseline visits  
5.  Documented recent history (within 18 months of patch 
testing) of inadequate response to treatment with topical 
medications and allergen avoidance 
6.   Able and willing to provide informed consent, participate in 
study visits, and undergo visit procedures. 

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Exclusion Criteria: 
1. Prior dupilumab use 
2. Treatment with a systemic immune-regulating medication 
within 3 months of the baseline visit or the patient’s prior patch 
testing, whichever is longer. Examples of these medications 
include azathioprine, methotrexate, mycophenolate mofetil, 
Janus kinase inhibitors, and phototherapy (including tanning 
booths). Cyclosporine or prednisone may not have been used 
within 1 month of the baseline visit. 
3. Treatment with other biologic agents, such as TNF inhibitors, 
anti-IL 17 agents, anti-IL 12/23 agents, or anti-IL 23 agents, 
within 4 months of baseline visit or the patient’s prior patch 
testing, whichever is longer.  
4. Use of rituximab within at 6 months (or until lymphocyte 
counts have normalized if longer than 6 months) of the baseline 
visit or the patient’s prior patch testing, whichever is longer. 
5. Treatment with topical corticosteroids, topical 
phosphodiesterase inhibitors or topical calcineurin inhibitors 
within 1 week before the baseline visit 
6.  Other active conditions, such as psoriasis, that may confound 
clinical evaluations of dermatitis and patient-reported symptoms. 

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Exclusion Criteria 
(continued) 
7. Increased risk of infection or reactivated infection, including 
history of human immunodeficiency virus, hepatitis B, hepatitis 
C, endoparasitic infections, receipt of a live attenuated vaccine 
within 3 months of the baseline visit, chronic or acute infection 
requiring treatment within 4 weeks of the baseline visit, 
immunosuppressed status (ie recurrent or resistant opportunistic 
infections) 
8. Malignancy within 5 years of the screening visit excluding 
local cutaneous squamous cell carcinoma, basal cell carcinoma 
or cervical carcinoma in situ that has been fully treated.  
9. Women who are or plan to become pregnant or breastfeed 
during study participation or are unable or not willing to use birth 
control during the study and for 4 months after the last dose of 
dupilumab. Options for birth control include abstinence, double 
barrier (ie male condom and female diaphragm), vasectomy, 
intrauterine device, and hormonal contraception. Females who 
have not had menses within 1 year of the baseline, bilateral 
tubal ligation, hysterectomy, and/or bilateral oophorectomy visit 
do not require additional methods contraception during study 
participation. 
10. Unstable condition or status, as per study investigator’s 
judgment, that may lead to more likely discontinuation from the 
study including but not limited to major, recurrent medical 
illnesses that may require hospital admission and/or 
discontinuation of dupilumab, surgery that would require 
discontinuation of dupilumab and/or major rehabilitation, inability 
to participate in all study visits and administer dupilumab. 
11. Resident outside of Massachusetts, Connecticut, Rhode 
Island, New Hampshire, Maine or Vermont state. 
12. Unable to use Zoom videoconferencing.
Criteria for Evaluation: 
(Efficacy, safety, 
stopping rules, etc.)
Statistics: 

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1 
INTRODUCTION 
1.1 
Background on Allergic Contact Dermatitis 
Allergic contact dermatitis (ACD) is a chronic, inflammatory dermatitis affecting 
millions of Americans yearly and has significant negative impacts on patient 
quality of life and the economy. Contact dermatitis has an estimated prevalence 
rate of 13.6 cases per 1000 population, with 8.4 million office visits, 4 million 
workdays, and $400 million lost yearly in the United States.1,2,3 Identification of 
allergens through patch testing and subsequent avoidance is the first-line 
treatment along with topical corticosteroids. However, in certain patients, such as 
those with implantable devices or occupational exposures, allergen avoidance is 
difficult or impossible and represents a major unmet clinical need. Dupilumab is a 
promising treatment for allergic contact dermatitis through its blockade of the 
cytokines IL-4 and IL-13 that are central in the differentiation and maintenance of 
Th2 cells and its ability to also normalize Th1, Th17, and Th22-mediated immune 
pathways.4 Blockade of this pathway in ACD patients and the study of their skin 
and blood before and after treatment offers a unique opportunity to improve our 
understanding of disease mechanisms in human ACD and the potential role for 
dupilumab in addressing this unmet need.  
1.2 
Role of T cells in Allergic Contact Dermatitis and 
Dupilumab 
Current treatment strategies for ACD include allergen avoidance and the use of 
topical or systemic immunosuppressive agents. However, for many patients 
allergen avoidance can negatively affect quality of life or be inadequate, 
particularly in cases of unavoidable occupational exposures or implanted 
devices. While allergic contact dermatitis was originally posited to be a Th1-
predominant disease, the important roles played by Th2, Th17 and Th22 cells is 
increasingly recognized. Activation of inflammatory pathways in ACD can be 
allergen specific, with differential upregulation of innate immune, Th1, Th2, Th17, 
and/or Th22 signaling. Specifically, nickel induces a strong Th1, Th17 and Th22 
response, while fragrance and rubber have preferential TH2 stimulation. This is 
in contrast to atopic dermatitis, a predominantly Th2-mediated inflammatory 
reaction driven by the cytokines IL-4, IL-5 and IL-13. In atopic dermatitis, the 
cytokines IL-4 and IL-13 are the main pathogenic cytokines. These instructive 
cytokines both induce activated naïve T cells to become Th2 cells and maintain 
the survival of Th2-derived memory T cells. These cytokines can also alter 
chemokine expression and trafficking to inflamed tissue. The IL-4 and IL-13 
receptors share the common subunit IL-4Rα. Dupilumab, an inhibitor of IL-4Rα, 
is FDA-approved for the treatment of atopic dermatitis. Despite its specific 
targeting of Th2-mediated pathology, it has also been shown to normalize Th1-,  

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and Th17-related gene expression in the skin of patients with atopic dermatitis. 
Therefore, we hypothesize that dupilumab will most likely benefit patients who 
have persistent allergic contact dermatitis to allergens that primarily elicit a Th2 
immune response (ie rubber and fragrance), but may also benefit patients who 
have sensitivities to allergens that primarily elicit Th1, Th17, and Th22 immune 
responses (ie nickel). We propose to test this hypothesis by treating patients who 
have failed allergen avoidance and skin directed therapy with dupilumab and 
monitoring their responses in the following ways before and after therapy: using 
well-established clinical parameters addressing skin inflammation and quality of 
life issues, assessing whether the most abundant T cell clones (defined as the 
top 5 most abundant clones present in the skin at patch test site before therapy) 
can still traffic to the skin after therapy, and quantifying the changes in the 
inflammatory Th1, Th2, Th17 and Th22-specific immune gene signatures before 
and after treatment. 
1.3 
Summary of Results of Investigational Program 
1.3.1 
Pharmacology of Dupilumab 
Dupilumab is a human monoclonal IgG4 antibody that inhibits interleukin-4 (IL-4) 
and interleukin-13 (IL-13) signaling by specifically binding to the IL-4Rα subunit 
shared by the IL-4 and IL-13 receptor complexes. Dupilumab inhibits IL-4 
signaling via the Type I receptor and both IL-4 and IL-13 signaling through the 
Type II receptor.  
Blocking IL-4Rα with dupilumab inhibits IL-4 and IL-13 cytokine-induced 
responses, including the release of proinflammatory cytokines, chemokines and 
IgE.  
1.3.2 
Human Pharmacokinetics of Dupilumab 
Absorption  
Following an initial subcutaneous (SC) dose of 600 mg, dupilumab reached peak 
mean ±SD concentrations (Cmax) of 70.1±24.1 mcg/mL by approximately 1 
week post dose.  
Steady-state concentrations were achieved by Week 16 following the 
administration of 600 mg starting dose and 300 mg dose either weekly (twice the 
recommended dosing frequency) or every other week. Across clinical trials, the 
mean ±SD steady-state trough concentrations ranged from 73.3±40.0 mcg/mL to 
79.9±41.4 mcg/mL for 300 mg administered every 2 weeks and from 173±75.9 
mcg/mL to 193±77.0 mcg/mL for 300 mg administered weekly. The bioavailability 
of dupilumab following a SC dose is estimated to be 64%. Distribution The 
estimated total volume of distribution was approximately 4.8±1.3 L.  

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Elimination The metabolic pathway of dupilumab has not been characterized. As 
a human monoclonal IgG4 antibody, dupilumab is expected to be degraded into 
small peptides and amino acids via catabolic pathways in the same manner as 
endogenous IgG. After the last steady-state dose of 300 mg Q2W or 300 mg QW 
dupilumab, the median times to non-detectable concentration (<78 ng/mL) are 10 
and 13 weeks, respectively.  
Dose Linearity Dupilumab exhibited nonlinear target-mediated pharmacokinetics 
with exposures increasing in a greater than dose-proportional manner. The 
systemic exposure increased by 30-fold when the dose increased 8-fold following 
a single dose of dupilumab from 75 mg to 600 mg (i.e., 0.25times to 2-times the 
recommended dose). Weight Dupilumab trough concentrations were lower in 
subjects with higher body weight. Immunogenicity Development of antibodies to 
dupilumab was associated with lower serum dupilumab concentrations. A few 
subjects who had high antibody titers also had no detectable serum dupilumab 
concentrations.  
Specific Populations 
Geriatric Patients  
In subjects who are 65 years and older, the mean ±SD steady-state trough 
concentrations of dupilumab were 69.4±31.4 mcg/mL and 166±62.3 mcg/mL, 
respectively, for 300 mg administered every 2 weeks and weekly. No dose 
adjustment in this population is recommended.  
Renal or Hepatic Impairment  
No formal trial of the effect of hepatic or renal impairment on the pharmacokinetics 
of dupilumab was conducted. 
Drug Interaction Studies  
Drug interaction studies have not been conducted with DUPIXENT. 
1.3.3 
Clinical Safety with Dupilumab SC Formulation 
1.3.3.1 
Drug-Related Adverse Events 
Conjunctivitis  
During the 52-week treatment period of concomitant therapy trial (Trial 3), 
conjunctivitis was reported in 16% of the DUPIXENT 300 mg Q2W + TCS group 
(20 per 100 subject-years) and in 9% of the placebo + TCS group (10 per 100 
subject-years) [see Warnings and Precautions (5.2)].  
Eczema Herpeticum and Herpes Zoster  

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The rate of eczema herpeticum was similar in the placebo and DUPIXENT 
groups.  
Herpes zoster was reported in <0.1% of the DUPIXENT groups (<1 per 100 
subject-years) and in <1% of the placebo group (1 per 100 subject-years) in the 
16-week monotherapy trials. In the 52-week DUPIXENT + TCS trial, herpes 
zoster was reported in 1% of the DUPIXENT + TCS group (1 per 100 subject-
years) and 2% of the placebo + TCS group (2 per 100 subject-years).  
Hypersensitivity Reactions  
Hypersensitivity reactions were reported in <1% of DUPIXENT-treated subjects. 
These included serum sickness reaction, serum sickness-like reaction, and 
generalized urticaria [see Contraindications (4), Warnings and Precautions (5.1), 
and Adverse Reactions (6.2)].  
Eosinophils  
DUPIXENT-treated subjects had a greater mean initial increase from baseline in 
eosinophil count compared to subjects treated with placebo in the monotherapy 
trials. Eosinophil counts declined to near baseline levels by Week 16. The initial 
increase in eosinophils was not observed in the 52-week DUPIXENT + TCS trial.  
In Trials 1, 2, and 3, the incidence of treatment-emergent eosinophilia (≥500 
cells/mcL) was similar in DUPIXENT and placebo groups. In Trials 1, 2, and 3, 
treatment-emergent eosinophilia (≥5,000 cells/mcL) was reported in <1% of 
DUPIXENT-treated patients and none in placebo-treated patients. In most cases, 
eosinophil counts declined to near baseline during study treatment. 
1.4 
Research Hypothesis 
Dupilumab will most likely benefit patients who have persistent allergic contact 
dermatitis to allergens that primarily elicit a Th2 immune response (ie rubber and 
fragrance) but may also benefit patients who have sensitivities to allergens that 
primarily elicit Th1, Th17 and Th22 immune responses (ie nickel). 
1.5 
Study Rationale 
One of the most innovative aspects of this proposal is the proposed combination 
of clinical and translational science to address a potential new cohort of patients 
that may benefit from the use of dupilumab. By ascertaining the efficacy of 
dupilumab in a cohort of patients using a combination of robust, well-
characterized, clinical scoring and state-of-the-art technologies to identify and 
quantify changes in T cell trafficking and inflammatory gene and protein 
signatures, we will determine the extent to which dupilumab dampens the T-cell 

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response to allergens. Not only are these studies novel in this disease, blockade 
of IL-4 and IL-13 will lead to a better understanding of allergen-specific disease 
pathogenesis. 
2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
To measure the degree to which 2+(strong)-3+(extreme) patch test site reactions 
are reduced by dupilumab. Based on the International Contact Dermatitis 
Research Group scoring system (? as a doubtful reaction, + as a mild reaction, 
possible erythema, infiltration, and papules, ++ as a strong reaction, erythema, 
infiltration, papules and vesicles, +++ as a very strong reaction, intense erythema, 
infiltration, and coalescing vesicles, IR as an irritant reaction), we will measure 
patch test site reactions at two time points, both prior to starting dupilumab (Week 
0 +72-120 hours) and 12 weeks after starting dupilumab. 
2.2 
Secondary Objectives 
Secondary endpoint 1: Number of patients who achieve a reduction in investigator 
global assessment (IGA) from 3 or greater at screen and baseline to 0 or 1 at Week 
6 and Week 12.  
Secondary endpoint 2a: To quantify the inflammatory markers (Th1, Th2, Th17, 
Th22 immune pathways) in the blood and skin of patients before and after 
dupilumab. Using novel nanostring-based gene expression assays and 
multispectral immunofluorescence we will quantify changes in key genes that are 
specific for the Th1, Th2, Th17, Th22 immune pathways in the skin and blood of 
patients before and after treatment with dupilumab. Secondary endpoint 2b: 
Changes in IGA from baseline to week 12. Other secondary endpoints: Change in 
baseline eczema-area-and-severity-index (EASI), body surface area (BSA), 
numerical rating scale (NRS) itch, dermatology life quality index (DLQI), and 
SLEEPYQ from baseline to Week 6 and Week 12.  
Secondary endpoint 3: To measure the reductions in the severity of clinical skin 
disease and quality of life scores with dupilumab treatment. We will measure 
changes in investigator global assessment (IGA; scored on a scale of 0-5 with 0 
being no disease and 5 being the most severe disease) from baseline to Week 6 
and Week 12.  
Secondary endpoint 4: To address whether dupilumab affects T cell trafficking, use 
high-throughput sequencing of the T-cell receptor (TCR HTS) to identify the unique 

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CDR3 sequence of the likely pathogenic T cell clones before therapy and quantify 
their relative frequency in the skin after dupilumab therapy. 
3 
ETHICAL CONSIDERATIONS 
3.1 
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as 
defined by the International Conference on Harmonization (ICH) and in 
accordance with the ethical principles underlying the United States Code of 
Federal Regulations, Title 21, Part 50 (21CFR50). Study procedures and 
guidelines are outlined in this protocol and any changes to the protocol or informed 
consent forms will be submitted for IRB approval prior to their use. Any serious 
breaches in GCP, such as those leading to risks to patients or study validity, will 
be reported to Regeneron. All team members involved in the study will have 
appropriate qualifications to complete their responsibilities. Anyone with a history 
of scientific misconduct or fraud or anyone against whom sanctions have been 
invoked will not participate in the study.  
3.2 
Institutional Review Board/Independent Ethics 
Committee 
The IRB will review and approve all study materials including the protocol, informed 
consent form, and any other written information provided to subjects. A copy of the 
Investigator Brochure or product labeling information provided to subjects should 
be given to the IRB. Other information required by institutional procedures or 
regulatory agencies should also be given to the IRB.  
3.3 
Informed Consent 
Informed consent requires that patients are clearly and fully informed about the 
purpose, risks, and any other important information related to the study in which 
they are agreeing to participate. The rights, safety, and well-being of individual 
patients take prescience over other considerations including those of scientific 
investigation and society. 
Investigators must provide a copy of the informed consent form, signed and dated 
by the subject and the investigator who conducted the discussion of informed 
consent. The informed consent form should be written in lay language that is easy 
to understand and must be approved by the IRB prior to its use. All revisions to the 
informed consent form, which should be done when new, pertinent information 

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related to subject consent arises, also require IRB approval. All subjects 
participating in the study should be notified of the changes to the informed consent 
form and discuss with the investigator whether they plan to continue in the study. 
During the informed consent process, adequate time must be given to subjects so 
that they may review and ask questions about the study. The investigator should 
document all discussions regarding informed consent.  
4 
INVESTIGATIONAL PLAN 
4.1 
Study Design and Duration 
Patients previously seen at the Contact Dermatitis and Occupational 
Dermatology Program at Brigham and Women’s Hospital that meet the inclusion 
criteria will be recruited. In addition, patients will be invited to participate in the 
study directly during their clinical visit. Patients may be identified and provided 
information about the study at the time of their patch testing visits and/or follow-
up appointments. Additionally, patients who have been patch tested that inform 
us they are not improving following the allergen avoidance recommendations 
may also be provided information about the study.
A cover letter describing the study, signed by PI will be sent to the subjects at 
least a week in advance of their scheduled study visit with the PI or Co-
Investigator. In addition, an informed consent document will be sent with the 
letter to them to read over and discuss with family and others (including their 
healthcare providers). If interested in participating in the study, the subject will be 
asked to bring the informed consent document to the visit with the PI or Co-
Investigator.   
Patients identified directly during the office visit will be approached by a study 
staff other than PI. They will be provided with a cover letter and the informed 
consent document to take home and read and discuss with family members. 
Subsequent follow-up may include contact via mail, post or phone calls to 
patients to provide additional information about the study.  
Patients who read the consent form at the clinic and feel comfortable enough to 
consent to participate in the study, may be enrolled right away. 
It will be emphasized that participation is purely voluntary and will not influence 
the care or ability to get care within our institution any provider. 
In person study visits will take place at the clinical rooms of the Center for Clinical 
Investigations (CCI), the Ambulatory Clinical Center at 221 Longwood Avenue. In 

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addition, virtual study visits will take place using Healthcare Secure Zoom. Prior 
to their scheduled study visits, a research assistant will prepare the 
administrative paperwork informed consent, information materials, prospective 
visit schedule and the physician questionnaires.  
We will recruit 30 patients with allergic contact dermatitis 18 years of age and older 
up to 6 months after patch testing with a documented IGA of at least 3 at baseline 
and screening visits, and at least one 2+ (strong) or 3+ (extreme) reaction on patch 
testing to participate in this open-label pilot study.  If more than one 2+ (strong) or 
3+ (extreme) reactions are present, up to two may be selected for evaluation in the 
study. Priority will be given to nickel, fragrance mix I or II, and rubber as these 
allergens have been studied previously with respect to their preferential T helper 
cell skewing. At the initial screening visit, demographic information will be obtained, 
inclusion and exclusion criteria as detailed in Section 4.2 will be reviewed, and 
informed consent obtained for those deemed eligible for enrollment. A single 
subcutaneous dose of 600 mg will be self-administered at week 0 +72-120 hours 
and 300 mg every 2 weeks thereafter for a total 10 weeks of therapy.  Subjects will 
be evaluated for improvement in primary and secondary endpoints using clinical 
examination and questionnaires during initial and follow-up visits at Week 0, Week 
6, and Week 12 as per Time and Events Schedule.  Patch test site reactions will 
also be evaluated 72 hours after the Week 0 and Week 12 visits. Skin biopsies will 
be taken at these two time points from both the patch test site reaction and from 
normal skin taken from a non-dermatitic area on the contralateral side of the body. 
For the Week 12 patch placement, a site contralateral to the Week 0 patch 
placement site will be chosen. If an area of persistent dermatitis other than the 
patch test site(s) is also present at week 12+72-120 hours an additional biopsy will 
be taken unless in an anatomic location not amenable to biopsy (face, hands, 
elbows, knees, genitals, feet). Serum samples will be obtained at four time-points 
including Week 0 (prior to patch placement), Week 0 +72-120 hours, Week 12 
(prior to patch placement), and Week 12 +72-120 hours. If subjects do not mount 
a 2+ (strong) or 3+ extreme reaction to the tested allergens at the Week 0 +72-120 
hour visit they will be discontinued from the study and will not receive dupilumab. 
These patients will be considered screen fails. Week 10 +72-120 hours will 
conclude the end of the treatment portion of the study. Week 12 +72-120 hours 
will conclude the subjects’ participation in the study. 
We developed a contingency plan in case there is a resurge of COVID, a 
pandemic, closure of facilities or other act of God that prevents the study visit 
schedule to be completed in person.  In such case, we will add a virtual visit 
component to our in-person visits to complete some of the research activities 
related to that visit. 
Please see the Time and Events Schedule for full details.  

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4.2 
Study Population 
For entry into the study, the following criteria MUST be met. 
4.2.1 
Inclusion Criteria 
The following inclusion criteria are required for patient participation in the study:  
1. At least 18 years of age 
2. At least one contact allergen with a 2+ (strong) or 3+ (extreme reaction) 
confirmed by patch testing within 18 months of the baseline visit that can be 
duplicated at the initiation of the study (placement at Week 0 and patch test 
reaction read at Week 0 +72-120 hours). 
3. Allergic contact dermatitis diagnosed clinically by the principle investigators 
who have expertise in allergic contact dermatitis  
4. Investigator’s global assessment score of at least 3 (range 0-4) at the 
screening and baseline visits  
5. Documented recent history (within 18 months of patch testing) of inadequate 
response to treatment with topical medications and allergen avoidance 
6. Able and willing to provide informed consent, participate in study visits, and 
undergo visit procedures.   
4.2.2  
Exclusion Criteria 
Any of the following exclusion criteria would prohibit patient participation in the 
study:  
1. Prior dupilumab use 
2. Treatment with a systemic immune-regulating medication within 3 months of 
the baseline visit or the patient’s prior patch testing, whichever is longer. 
Examples of these medications include azathioprine, methotrexate, 
mycophenolate mofetil, Janus kinase inhibitors, and phototherapy (including 
tanning booths). Cyclosporine or prednisone may not have been used within 1 
month of the baseline visit. 
3. Treatment with other biologic agents, such as TNF inhibitors, anti-IL 17 
agents, anti-IL 12/23 agents, or anti-IL 23 agents, within 4 months of baseline 
visit or the patient’s prior patch testing, whichever is longer.  

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4. Use of rituximab within at 6 months (or until lymphocyte counts have 
normalized if longer than 6 months) of the baseline visit or the patient’s prior 
patch testing, whichever is longer. 
5. Treatment with topical corticosteroids, topical phosphodiesterase inhibitors or 
topical calcineurin inhibitors within 1 week before the baseline visit 
6. Other active conditions, such as psoriasis, that may confound clinical 
evaluations of dermatitis and patient-reported symptoms. 
7. Increased risk of infection or reactivated infection, including history of human 
immunodeficiency virus, hepatitis B, hepatitis C, endoparasitic infections, receipt 
of a live attenuated vaccine within 3 months of the baseline visit, chronic or acute 
infection requiring treatment within 4 weeks of the baseline visit, 
immunosuppressed status (ie recurrent or resistant opportunistic infections) 
8. Malignancy within 5 years of the screening visit excluding local cutaneous 
squamous cell carcinoma, basal cell carcinoma or cervical carcinoma in situ that 
has been fully treated.  
9. Women who are or plan to become pregnant or breastfeed during study 
participation or are unable or not willing to use birth control during the study and 
for 4 months after the last dose of dupilumab. Options for birth control include 
abstinence, double barrier (ie male condom and female diaphragm), vasectomy, 
intrauterine device, and hormonal contraception. Females who have not had 
menses within 1 year of the baseline, bilateral tubal ligation, hysterectomy, 
and/or bilateral oophorectomy visit do not require additional methods 
contraception during study participation. 
10. Unstable condition or status, as per study investigator’s judgment, that may 
lead to more likely discontinuation from the study including but not limited to 
major, recurrent medical illnesses that may require hospital admission and/or 
discontinuation of dupilumab, surgery that would require discontinuation of 
dupilumab and/or major rehabilitation, inability to participate in all study visits and 
administer dupilumab. 
11. Resident outside of Massachusetts, Connecticut, Rhode Island, New 
Hampshire, Maine or Vermont state. 
12. Unable to use Zoom videoconferencing.   
4.2.2 
Discontinuation of Subjects from Treatment 
Patients may withdraw from the study for any reason and at any time and will not 

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be subject to consequences because of their withdrawal. The investigators may 
also withdraw a patient from the study for any reason such as to protect patient 
safety, administrative changes, or protocol deviation. Patients who withdraw or 
are withdrawn from the study will undergo early termination study assessments. 
5 
TREATMENTS 
5.1 
Study Treatment: Dupilumab 
Patients will receive dupilumab subcutaneously 300 mg every 2 weeks during the 
10-week treatment period following a loading dose of 600 mg at Week 0 +72-120 
hours. The study staff will demonstrate to the patient administration of study drug 
at Week 0 +72-120 hours through Zoom video conference and will administer the 
first loading dose injection at the in-person portion of the visit on the same day. 
The study staff will observe the patient self-administer the second loading dose 
injection. After the initial dose dupilumab will be self-administered by patients off-
site. Injection sites may include the four quadrants of the abdomen (avoiding the 
umbilicus and waist), upper thigh, and upper arms. The same site should not be 
injected for two consecutive doses of dupilumab. A dupilumab administration log 
will also be provided to patients.  
5.1.1 
Identification 
Dupilumab injection is dispensed as a 300 mg/syringe (300 mg/2 mL) for 
subcutaneous administration, which contains L-arginine hydrochloride(10.5 
mg), L-histidine (6.2 mg), polysorbate 80 (4 mg), sodium acetate (2 
mg), sucrose (100 mg), and water for injection, pH 5.9.  
5.1.2 
Packaging and Labeling 
Dupilumab SC is supplied in a box of 2 syringes with an open-label.  
5.1.3 
Handling and Dispensing 
Dupilumab will be stored by the study pharmacy under refrigeration (approximately 
2°C to 8°C). 

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5.2 
Drug Ordering and Accountability 
5.2.1 
Initial Orders 
Initial dupilumab orders will be placed through the Regeneron project manager. 
5.2.2 
Re-Supply 
Re-supply dupilumab orders will be placed through the Regeneron project 
manager.  
5.3 
Timing of Dose for Each Subject 
Two doses of dupilumab, 300 mg/2 mL, will be administered subcutaneously using 
the prefilled syringe at week 0 +72-120 hours and one dose dupilumab, 300 mg/2 
mL, will be administered subcutaneously every two weeks thereafter continuing 
until week 10 +72-120 hours.  
5.3.1 
Dose Modifications 
Not applicable. 
5.4 
Blinding/Unblinding 
Not applicable. 
5.5 
Concomitant Treatments 
See inclusion and exclusion criteria (4.2.1 and 4.2.2) for details on concomitant 
treatments allowed and not allowed for study participation. 
5.6 
Treatment Compliance 
Patients will be given a dupilumab dosing diary that will be collected at the 
completion of the study to monitor treatment compliance.  
6 
STUDY ASSESSMENTS AND PROCEDURES 
6.1 
Time and Events Schedule 
Time and events schedule is detailed in the table below: 
Visit Number 
1 
Screening 
2 
Week 
0 
3 
Week 0 
+72-120 
Hours 
4 
Week 
6 
5 
12 
Weeks 
6 
12 Weeks 
+72-120 
hours 
7 
Early 
Termination 
/Unscheduled 
Visit

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Day (+/- 3 days)
-34 to 0
1
4
42
84
87
N/A
Informed eConsent
X
Inclusion/Exclusion Criteria
X
Medical History
X
Prior/Concurrent Medications
X
X
Safety Assessments
Adverse Events
X
X
X
X
X
X
Clinical Efficacy Assessments
Patch Test Site Reaction
X
X
IGA
X
X
X
X
X
EASI
X
X
X
X
BSA
X
X
X
X
Patient-Reported Outcomes
DLQI
X
X
X
X
NRS Itch
X
X
X
SLEEPYQ
X
X
X
X
Distribute Diaries (Allergen 
Avoidance and Dupilumab Dosing)
X 
Collect Diaries (Allergen Avoidance 
and Dupilumab Dosing)
X 
X 
Laboratory Assessments
Pregnancy Test
X
X
X
X
X
Biomarker Skin Sample
X
X*
Biomarker Serum Sample
X
X
X
X
Medication Dosing
In-Office Dosing
X
Dispense Study Medication
X
X
Patch Testing
Patch Test Material Placement
X
X
Patch Test Material Removal
Photographs
Patch Test Site Photographs
X
X
X
X
Dermatitis Photographs 
X 
X 
X 
*In addition to the allergen patch site and normal skin, an additional biopsy will be done on an  
area of persistent dermatitis if present unless in an anatomic location not amenable to biopsy 
(face, hands, elbows, knees, genitals, feet). 
6.2 
Study Materials 
Dupilumab will be provided by Regeneron at no cost. 
6.3 
Safety Assessments 
All subjects who receive a dose of dupilumab will be evaluated for safety. Our 
clinical trials team will provide periodic audits internally for safety assessments. 
The investigator will determine the severity of each adverse event as mild, 
moderate, severe, or very severe. The relationship between the adverse event and 
study drug will also be determined. Dupilumab may be discontinued due to lack of 
effectiveness, patient is lost-to-follow-up or withdraws consent, protocol deviation, 
or adverse event that may cause severe or permanent harm according to the 
judgment of the study investigator or an adverse event of grade 2 or more related 
to dupilumab defined by the National Cancer Institute Common Terminology 
Criteria 
for 
Adverse 
Events, 
Version 
4.0 
(CTCAE: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm). 

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Notification will be provided to Regeneron if a patient discontinues dupilumab and 
the reason will be recorded in the patient’s medical and study records.  
6.4 
Efficacy Assessments 
6.4.1 
Primary Efficacy Assessment 
The following clinical assessments will provide outcome data:  
Number of patients who achieve a reduction in patch test site reactions from 2+-
3+ at baseline to "?" or no reaction at week 12 +72-120 hours. 
6.4.2 
Secondary Efficacy Assessments 
6.4.2.1      Secondary Clinical Endpoints 
Secondary endpoint 1: Number of patients who achieve a reduction in investigator 
global assessment (IGA) from 3 or greater at screen and baseline to 0 or 1 at Week 
6, and Week 12.  
Secondary endpoint 2a: To quantify the inflammatory markers (Th1, Th2, Th17, 
Th22 immune pathways) in the blood and skin of patients before and after 
dupilumab. Secondary endpoint 2b: Changes in IGA from baseline to week 12. 
Other secondary endpoints: Change in baseline eczema-area-and-severity-index 
(EASI), body surface area (BSA), numerical rating scale (NRS) itch, dermatology 
life quality index (DLQI), and SLEEPYQ from baseline to Week 6 and Week 12.  
Secondary endpoint 3: Changes in IGA from baseline to Week 6 and Week 12. 
Other secondary endpoints: Change in baseline eczema-area-and-severity-index 
(EASI), body surface area (BSA), numerical rating scale (NRS) itch, dermatology 
life quality index (DLQI), and SLEEPYQ from baseline to Week 6 and Week 12. 
Secondary endpoint 4: Identification and quantification of the most prevalent T cell 
clones in the skin before therapy and how those clones change after therapy using 
high-throughput sequencing of the TCRB gene. 
6.4.2.2      Secondary Non-Clinical Endpoints
Serum samples will be collected at baseline and week 12 prior to patch placement 
for analysis of inflammatory cells and markers. Additionally skin and serum 

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samples will be collected for analysis of inflammatory cells and markers 72 hours 
after patch placement at baseline and week 12. We will also collect one additional 
biopsy from an area of persistent, chronic dermatitis if present after the 10-week 
course of dupilumab. Skin biopsies will be collected at 72 hours after patch testing 
from the sites of allergen placement and will be initially placed in saline. Blood 
samples will also be collected on the same day. DNA and RNA will be isolated 
from PBMCs and 300 um of tissue. The isolated DNA will be subjected to TCR 
HTS of the TCRB gene before and after therapy. We will determine the CDR3 
sequence of the top 5 most prevalent clones in the skin of patch tested skin before 
therapy, which likely represents at least one of the pathogenic T cell clones specific 
to the allergen. We will quantify the presence and abundance of those same clones 
in the blood and patch tested skin after therapy as a measure of T cell trafficking 
(ie ability of those same T cell clones being able to reenter skin at site of specific 
allergen placement may be inhibited after dupilumab therapy). The RNA will be 
subjected to multiplex gene expression analysis of 594 human immune genes to 
specifically characterize the Th1, Th2, Th17, and Th22 skewing of the immune 
microenvironment as well as quantify the expression of alarmins and proteases 
known to be important in the elicitation phase of allergic contact dermatitis. These 
gene signatures and immune cell subtypes analyses will be confirmed at the 
protein level with multispectral immunofluorescence on the skin and flow cytometry 
in the blood. 
Novel Technologies to be used: High throughput sequencing of the T cell receptor 
CDR3 region (TCR HTS) is a powerful technology that measures the CDR3 
sequences and the relative frequencies of all T cells in a biologic specimen, 
allowing study of individual T cell clones as well as studies of the entire T cell 
population in a patch tested skin lesion. Tyramide signaling amplification 
immunostaining/multi-spectral imaging and automated image analysis. This 
technology provides visualization of up to 6 proteins of interest for state-of-the-art 
phenotypic and functional analyses compared to standard IHC. Tyramide signaling 
amplification (TSA) allows for sequential immunostaining of the same tissue 
section for up to six different markers. We will utilize the revolutionary Perkin-Elmer 
Mantra Quantitative Pathology Imaging Microscope which scans each slide and 
extracts the data from each individual fluorescence channel so that each marker 
can be displayed in separate images. This imaging technology allows the 
equivalent of flow cytometry profiling on tissue sections and it works particularly 
well on FFPE samples, as shown below in Preliminary Studies. NanoString-based 
technologies. NanoString-based gene expression analysis using their human 
immunology panel allows robust and direct quantification of 594 mRNA sequences 
in FFPE tissues, allowing quantitative gene profiling studies utilizing our skin 
biopsy specimens. This panel allows for immune cell subset analysis of Th1, Th2, 
Th17 and Th22 cells by using a subset of genes whose expression is largely 
specific to certain immune cell populations. The underlying assumption from this 

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model is that these characteristic genes are expressed only in that cell type and 
are expressed at the same level in each cell (these are essentially reference genes 
specific to individual cell types). Under this model, a cell type’s abundance can be 
measured as the average logscale expression of its characteristic genes that are 
concordant within the sample. This allows an unbiased comparison of relative 
abundance of cell types between sample groups. It also allows for comparisons 
between cell types. 
7 
ADVERSE EVENT REPORTING 
7.1 
Adverse Events 
Adverse events include any new or worsening of a medical condition. Adverse 
events are not limited to those related to study drug.  
7.1.1 
Serious Adverse Events 
A serious adverse event may include those that result in death, life-threatening 
events, inpatient hospitalization or prolonged hospitalization, disability/incapacity, 
congenital anomaly/birth defect, important medical event, suspected transmission 
of an infectious agent through the study drug, and the case of the current study 
pregnancy.  
7.1.2 
Non-serious Adverse Events 
A non-serious adverse event includes adverse events that are not considered 
serious adverse events. 
7.1.3 
Assignment of Adverse Event Intensity and Relationship to 
Dupilumab 
Adverse events are graded as mild (grade 1) for those that are noticeable but easily 
tolerated; moderate (grade 2) for those that cause enough discomfort that there is 
some interference with usual activity; severe (grade 3) for those that lead to an 
inability to perform usual activities; very severe (grade 4) for those that are 
debilitating causing significant incapacitation even with symptomatic treatment. An 
adverse event may be related (reasonable causal relationship between dupilumab 
administration and the event) or not related (no reasonable causal relationship 
between dupilumab administration and the event). A reasonable causal 
relationship denotes that there are facts or other arguments suggesting a positive 
causal relationship.  

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7.2 
Collection and Reporting 
When documenting adverse events the diagnosis if preferable to symptoms. 
Information that should be collected for adverse events include: onset, duration, 
intensity, and seriousness of the event, relationship between the event and 
dupilumab, resulting action taken, and any required treatments (should be 
documented in the medical record).  
7.2.1 
Serious Adverse Event Collecting and Reporting  
Serious adverse event collection should begin at the time that informed consent is 
obtained. All serious adverse events must be collected and reported, including 
those that occur within 30 days after the final dupilumab dose. If a serious adverse 
event occurs after this period, but is related to dupilumab or procedures performed 
in the study these should also be reported. If there is uncertainty whether an event 
is a serious one, a serous adverse event report should be completed. All serious 
adverse events, whether related or not related  to dupilumab, must be reported to 
Regeneron within 24 hours.  
7.2.2 
Non-Serious Adverse Events (NSAEs) Collecting and Reporting 
Non-serious adverse event collection should begin at the time that dupilumab is 
first administered. These events should be monitored until they resolve or become 
stable. Non-serious adverse events may also become serious adverse events.  
7.3 
Pregnancy 
Pregnancy should be considered a serious adverse event in the case when a 
subject is found to be pregnant while taking dupilumab.  
8 
DATA MONITORING COMMITTEE 
Not applicable. 
9 
STATISTICAL CONSIDERATIONS 
9.1 
Sample Size Determination 
Open label, pilot design: Descriptive statistics to report baseline subject 
characteristics A sample size of 11 participants achieves 80% power to detect a 
mean change of -1.0 (i.e., one less reaction on average) with an estimated 
standard deviation of 1.0 using a two-sided Wilcoxon test with significance level 

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α=0.05 and assuming the actual distribution of change is normal. Upweighting of 
10-25% would add conservatively to our ability to detect a change and is reflected 
in the final sample size estimation of 14 subjects. Therefore, we need a minimum 
of 14 subjects who complete the study to have enough statistical power. In order 
to accomplish this, we will aim to enroll a maximum of 30 subjects. 
9.2 
Populations for Analyses 
Study population will be subjects ages 18 years and older of any race/ethnicity and 
gender, with clinically diagnosed allergic contact dermatitis who have not improved 
following allergen avoidance and topical therapies within 6 months of patch testing. 
9.3 
Endpoint Definitions 
Investigator’s Global Assessment (IGA) score 
The investigator’s global assessment is a physician-reported global assessment 
of disease activity (range 0-4) with 0 being clear and 4 being severe.  
Body Surface Area (BSA) 
The body surface area is a physician-reported measure of the amount of disease 
involvement. The patient’s palm size approximates 1% of body surface area 
involvement. 
Eczema Area and Severity Index (EASI) score 
The eczema-area-and-severity-index score is a composite score of disease 
severity and extent of disease distribution. It was initially developed for evaluation 
of eczema. Disease severity (range 0-3; 0 being no disease and 3 being severe 
disease) is a measure of redness, thickness/induration, scratching, and 
lichenification. Each characterization is measured separately for body regions 
(head and neck, trunk, upper extremities, and lower extremities) to calculate a 
regional score. The total score is a sum of the four body regions (range 0-72).  
Numerical Rating Scale (NRS) itch 
The numerical rating scale for itch is a patient-reported measure of itch (range 0-
10) with 0 being no itch and 10 being the worst imaginable itch. 
Dermatology Life Quality Index (DLQI) 

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The Dermatology Life Quality Index is a 10-question, patient-reported instrument 
to assess impact of skin diseases on patient quality of life.  
SLEEPY-Q 
The Sleepy-Q is a patient-reported questionnaire that consists of 18 questions. It 
assesses three dimensions of sleep in patients with inflammatory skin conditions: 
sleep disturbance, causes of sleep disturbance and impairment related to sleep 
disturbance.  
9.4 
Analyses 
9.4.1 
Demographics and Baseline Characteristics 
Demographics and baseline disease characteristics including age, gender, 
ethnicity, age of onset of allergic contact dermatitis, body areas of dermatitis 
involvement, prior treatments for allergic contact dermatitis (including prescription 
therapies and prior recommended allergen avoidance strategies) will be 
documented at the initial screening visit. 
9.4.2 
Safety Analyses 
Subjects will be questioned about experiencing any adverse events at every follow-
up visit. 
9.4.3 
Efficacy Analyses 
At the time of enrollment, clinical parameters will be measured and recorded 
including their prior positive patch test reactions type and strength, IGA, EASI, 
BSA, DLQI, NRS itch, and SLEEPYQ. Patients will also be provided with a diary 
to record their allergen avoidance strategies and dulpilumab dosing. A sample of 
blood will also be taken. At the week 0 +72-120 hours study visit their patch test 
site reaction will be recorded. Samples of skin will be placed on sterile, saline 
soaked gauze and transported back to the Clark laboratory at 221 Longwood 
Avenue. One portion of the skin will be embedded in OCT and frozen at -20°C for 
future cryosectioning and the second portion of the skin will be placed in culture 
for the isolation of skin T cells. T cells and dendritic cells will then be analyzed by 
molecular and cellular techniques including TCR sequencing, nanostring, and 
multiplex fluorescence. A second sample of blood will also be taken. DNA will be 
extracted from blood samples and TCR sequencing will be done through 
collaborators at Adaptive as a fee for service arrangement. Isolated DNA from 
biopsies and blood samples will be sent, these will be coded with no identifiable 
information shared. Any leftover samples may be stored for future projects if a 
subject provides this optional consent.

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The primary clinical efficacy endpoint will be the number of patients who achieve 
a reduction in patch test site reactions from 2+-3+ at baseline to "?" or no reaction 
at week 12 +72-120 hours. Secondary endpoints will include number of patients 
who achieve a reduction in investigator global assessment (IGA) from 3 or greater 
at screen and baseline to 0 or 1 at Week 6, and Week 12; quantification of the 
inflammatory markers (Th1, Th2, Th17, Th22 immune pathways) in the blood and 
skin of patients before and after dupilumab; changes in IGA from baseline to week 
12. Other secondary endpoints: Change in baseline eczema-area-and-severity-
index (EASI), body surface area (BSA), numerical rating scale (NRS) itch, 
dermatology life quality index (DLQI), and SLEEPYQ from baseline to Week 6 and 
Week 12; changes in IGA from baseline to Week 6 and Week 12; changes in 
baseline eczema-area-and-severity-index (EASI), body surface area (BSA), 
numerical rating scale (NRS) itch, dermatology life quality index (DLQI), and 
SLEEPYQ from baseline to Week 6 and Week 12;i dentification and quantification 
of the most prevalent T cell clones in the skin before therapy and how those clones 
change after therapy using high-throughput sequencing of the TCRB gene. 
10 
STUDY MANAGEMENT 
10.1 
Compliance with the Protocol 
10.1.1 
Compliance with the Protocol and Protocol Revisions 
Study procedures are performed according the protocol, approved by the IRB. 
Signed approval by the IRB should be sent to the study sponsor. If there is an 
immediate hazard to study subjects, deviation or change in the protocol may be 
made prior to IRB approval. The deviation or change should be submitted as soon 
as possible to the IRB for review, the study sponsor, and any regulatory authorities 
as required by local regulations.  
If there is a study amendment that significantly changes the study design and/or 
potential subject risk, the informed consent form must be revised and approved by 
the IRB, informed consent must be obtained from all subjects in the study for those 
affected by the amendment and who agree to continue their participation, and used 
for all new subjects. 

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10.2 
Records Retention  
10.2.1 
Records Retention 
All study documents will be retained for the maximum period required by applicable 
regulations/guidelines or institution procedures, whichever is longer.  
10.2.2 
Study Drug Records  
The research pharmacy will maintain a record of dupilumab study drug.  

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11 
LIST OF ABBREVIATIONS 
ACD 
Allergic Contact Dermatitis 
BSA 
Body Surface Area 
GCP 
Good Clinical Practice 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLQI 
Dermatology Quality of Life Index 
EASI 
Eczema Area and Severity Index 
HTS 
High Throughput Sequencing 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment 
IRB 
Internal Review Board 
NRS 
Numerical Rating System 
TNF 
Tumor Necrosis Factor 

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12 
REFERENCES 
1. Kaplan et al. Early immune events in the induction of allergic contact 
dermatitis. Nat Rev Immunol 2012;12:114-124.
2. Israel et al. Skin conditions and related need for medical care among persons 
1-74 years. National Health Survey, November 1978, Series 11, Number 212; 1-
72.
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