A Phase IIa, Double-Blind, Randomised, Placebo-controlled, Exploratory Study to Evaluate the Safety, Biological Activity and Pharmacokinetics of GBR 830 in Adults With Moderate-to-Severe Atopic Dermatitis
Phase: PHASE2
Conditions: Atopic Dermatitis
Sponsor: Ichnos Sciences SA

Title: A Phase IIa, Double-Blind, Randomized, Placebo-Controlled, Exploratory Study to Evaluate 
the Safety, Biological Activity and Pharmacokinetics of GBR 830 in Adult Patients With 
Moderate-to-Severe Atopic Dermatitis 
 
NCT02683928 
 
Document Date: 16-Feb-2017 

Glenmark  
CONFIDENTIAL 
Page 1 of 98 
 
 
CLINICAL STUDY PROTOCOL 
 
Protocol Title 
A Phase IIa, Double-Blind, Randomized, Placebo-controlled,  
Exploratory Study to Evaluate the Safety, Biological Activity and 
Pharmacokinetics of GBR 830 in Adult Patients With Moderate-
to-Severe Atopic Dermatitis 
Protocol Number 
GBR 830-201 
Name of Investigational 
Product/Code 
GBR 830 
Phase of Development 
IIa 
Sponsor 
Glenmark Pharmaceuticals SA 
Protocol Version 
Version 4.0   
Date 
16-Feb-2017 
Supersedes 
Version 3.0 
 
PROTOCOL HISTORY 
Original protocol 
Version 1.0, 12-Oct-2015 
Protocol Amendment 1 
Version 2.0, 19-May-2016 
Protocol Amendment 2 
Version 3.0, 07-Nov-2016 
Protocol Amendment 3 
Version 4.0, 16-Feb-2017 
 
Statement of Confidentiality 
This protocol is a confidential document owned by Glenmark (Sponsor).  Any unpublished 
information contained in it may not be disclosed to a third party without prior written approval 
of the Sponsor.  However, the document may be disclosed to an Institutional Review 
Board/Independent Ethics Committee or a statutory regulatory authority under a similar 
condition of confidentiality. 
 

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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ..................................................................................................1 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF TABLES ...........................................................................................................................6 
LIST OF FIGURES .........................................................................................................................6 
1. 
ABBREVIATIONS AND SPECIALIST TERMS .......................................................7 
2. 
PROTOCOL SYNOPSIS ...........................................................................................11 
3. 
INVESTIGATOR’S SIGNATURE ............................................................................23 
4. 
SPONSOR’S SIGNATURE .......................................................................................24 
5. 
BACKGROUND INFORMATION ...........................................................................25 
5.1. 
Introduction .................................................................................................................25 
5.2. 
Investigational Product: Mechanism of Action ..........................................................26 
5.3. 
Preclinical Experience ................................................................................................26 
5.4. 
Clinical Experience .....................................................................................................27 
5.4.1. 
Summary of Safety .....................................................................................................28 
5.5. 
Study Rationale ...........................................................................................................29 
5.6. 
Benefit-Risk Assessment ............................................................................................30 
6. 
STUDY OBJECTIVE(S) ............................................................................................31 
6.1. 
Primary Objective(s) ...................................................................................................31 
6.2. 
Secondary Objective(s) ...............................................................................................31 
6.3. 
Exploratory Objective(s) ............................................................................................31 
7. 
STUDY DESIGN .......................................................................................................32 
7.1. 
Study Type/Design .....................................................................................................32 
7.1.1. 
Screening Phase ..........................................................................................................33 
7.1.2. 
Treatment Phase ..........................................................................................................34 
7.1.3. 
Follow-up ....................................................................................................................34 
7.1.4. 
Extension Phase ..........................................................................................................34 
7.2. 
Discussion of Study Design, Including Choice of Control Groups ............................34 
8. 
STUDY ENDPOINT(S) .............................................................................................35 
8.1. 
Primary Endpoint(s) ....................................................................................................35 

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8.2. 
Secondary Endpoint(s) ................................................................................................35 
8.3. 
Exploratory Endpoint(s) .............................................................................................35 
8.4. 
Appropriateness of Measurements .............................................................................36 
9. 
PATIENT SELECTION AND WITHDRAWAL CRITERIA ...................................36 
9.1. 
Inclusion Criteria ........................................................................................................36 
9.2. 
Exclusion Criteria .......................................................................................................38 
9.3. 
Study Termination, Patient Discontinuation/Withdrawal Criteria .............................40 
9.3.1. 
Study Termination Criteria .........................................................................................40 
9.3.2. 
Patient Discontinuation/Withdrawal Criteria .............................................................40 
9.3.3. 
Sponsor Discontinuation Criteria ...............................................................................41 
9.4. 
Prior and Concomitant Medication(s) ........................................................................42 
9.4.1. 
Rescue Medication(s) .................................................................................................43 
9.5. 
Lifestyle and/or Dietary Restrictions ..........................................................................43 
9.5.1. 
Contraception ..............................................................................................................44 
10. 
TREATMENT OF PATIENTS ..................................................................................45 
10.1. 
Treatments Administered ............................................................................................45 
10.1.1. 
Administration ............................................................................................................45 
10.1.2. 
Treatment Compliance ................................................................................................45 
10.1.3. 
Treatment of Investigational Product Overdose .........................................................46 
10.2. 
Identity of Investigational Product(s) .........................................................................46 
10.2.1. 
Chemical Name and Structural Formula of GBR 830 ................................................46 
10.2.2. 
Placebo/Control/Comparator ......................................................................................46 
10.2.3. 
Packaging and Labelling of Investigational Product(s) ..............................................46 
10.3. 
Allocation to Treatment Groups .................................................................................47 
10.4. 
Blinding and Unblinding Procedures ..........................................................................48 
10.5. 
Investigational Product(s) Preparation, Receipt, Storage, Dispensing and 
Accountability .............................................................................................................48 
11. 
TIMING OF STUDY PROCEDURES AND ASSESSMENTS ................................49 
11.1. 
Screening: Visit 1 .......................................................................................................51 
11.2. 
Dosing visits (Visits 2 and 7) ......................................................................................52 

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11.3. 
Follow-up Visits 3 and 8 (Days 4±1 and 32±1) .........................................................53 
11.4. 
Follow-up Visits 4 and 9 (Days 8±1 and 36±1) .........................................................53 
11.5. 
Follow-up Visits 5 and 10 (Days 15±1 and 43±1) .....................................................53 
11.6. 
Follow-up Visits 6 and 11 (Days 22±2 and 50±2) .....................................................54 
11.7. 
Follow-up Visits 12 and 13 (Days 57±2 and 71±2) ...................................................54 
11.8. 
Follow-up Visits (end of study) assessments on Day 85 (±2) include the 
following: ....................................................................................................................54 
11.9. 
Early Withdrawal Visit ...............................................................................................55 
11.10. 
Telephone Monitoring ................................................................................................55 
12. 
STUDY PROCEDURES AND ASSESSMENTS......................................................56 
12.1. 
Demographic and Other Pretreatment Assessments ...................................................56 
12.1.1. 
Demography ...............................................................................................................56 
12.1.2. 
Medical History and Physical Examinations at Screening .........................................56 
12.1.3. 
QuantiFERON Gold Blood TB Test...........................................................................56 
12.2. 
Efficacy Assessments .................................................................................................56 
12.2.1. 
EASI ...........................................................................................................................56 
12.2.2. 
SCORAD ....................................................................................................................56 
12.2.3. 
IGA .............................................................................................................................57 
12.2.4. 
NRS.............................................................................................................................57 
12.2.5. 
DLQI ...........................................................................................................................57 
12.3. 
Pharmacokinetic, Pharmacodynamic, Biomarker and Pharmacogenomic 
Assessments ................................................................................................................57 
12.3.1. 
Pharmacokinetic Assessments ....................................................................................57 
12.3.2. 
Immunogenicity Assessments ....................................................................................58 
12.3.3. 
Biomarker Assessments ..............................................................................................58 
12.3.4. 
Pharmacogenomic Assessments .................................................................................59 
12.4. 
Safety Assessments .....................................................................................................59 
12.4.1. 
Study Stopping Rules and Follow-up Criteria ............................................................59 
12.4.2. 
Adverse Events ...........................................................................................................59 
12.4.3. 
Serious Adverse Events ..............................................................................................62 
12.4.4. 
Pregnancy ...................................................................................................................63 

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12.4.5. 
Collection and Recording of AEs and SAEs ..............................................................64 
12.4.6. 
Clinical Laboratory Tests ...........................................................................................65 
12.4.7. 
Vital Signs ..................................................................................................................66 
12.4.8. 
Physical Examination .................................................................................................66 
12.4.9. 
ECG ............................................................................................................................66 
12.4.10. 
Infusion Reactions ......................................................................................................67 
12.4.11. 
Confirmation of Medical Care by Another Physician ................................................67 
13. 
DATA ANALYSIS AND STATISTICAL METHODS ............................................67 
13.1.1. 
Sample Size ................................................................................................................68 
13.2. 
Analysis Sets ...............................................................................................................68 
13.3. 
Patient Disposition ......................................................................................................69 
13.4. 
Demographic and Other Baseline Characteristics ......................................................69 
13.5. 
Efficacy Analyses .......................................................................................................69 
13.5.1. 
Analysis of Primary Efficacy Endpoint(s) ..................................................................69 
13.5.2. 
Analysis of Secondary Efficacy Endpoint(s) ..............................................................69 
13.5.3. 
Analysis of Exploratory Efficacy Endpoint(s) ...........................................................70 
13.6. 
Pharmacokinetic, Pharmacodynamic, Biomarker, and Pharmacogenomic/ 
Pharmacogenetic Analyses .........................................................................................70 
13.6.1. 
Pharmacokinetic Analyses ..........................................................................................70 
13.6.2. 
Immunogenicity Analyses ..........................................................................................70 
13.6.3. 
Biomarker Analyses ....................................................................................................70 
13.7. 
Safety Analyses ..........................................................................................................70 
13.7.1. 
Extent of Exposure .....................................................................................................70 
13.7.2. 
Adverse Events ...........................................................................................................71 
13.7.3. 
Laboratory Values ......................................................................................................71 
13.7.4. 
Vital Signs ..................................................................................................................71 
13.7.5. 
Electrocardiograms .....................................................................................................71 
13.7.6. 
Physical Examination .................................................................................................71 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................71 
14.1. 
Procedures for Monitoring Compliance .....................................................................72 

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14.2. 
Inspection ....................................................................................................................72 
14.3. 
Audit ...........................................................................................................................72 
15. 
ETHICS ......................................................................................................................72 
15.1. 
Ethics Committee Approval .......................................................................................72 
15.2. 
Ethical Conduct of the Study ......................................................................................73 
15.3. 
Informed Consent Process ..........................................................................................74 
15.4. 
Approval of the Protocol and Amendments ...............................................................74 
15.5. 
Protocol Deviation ......................................................................................................75 
16. 
DATA HANDLING AND RECORD KEEPING ......................................................75 
16.1. 
Data Management .......................................................................................................75 
16.2. 
Direct Access to Source Data/Documents ..................................................................75 
16.3. 
Confidentiality and Intellectual Property ....................................................................76 
16.4. 
Record Retention ........................................................................................................76 
17. 
FINANCING AND INSURANCE .............................................................................77 
18. 
PUBLICATION POLICY ..........................................................................................77 
19. 
DISCONTINUATION OF STUDY ...........................................................................77 
20. 
REFERENCES ...........................................................................................................78 
APPENDIX 1. SCHEDULE OF EVENTS .................................................................................80 
APPENDIX 2. LIST OF CLINICAL LABORATORY TESTS .................................................84 
APPENDIX 3. NAME(S) OF CLINICAL LABORATORIES AND OTHER 
DEPARTMENTS AND/OR FACILITIES PARTICIPATING IN THE 
STUDY .......................................................................................................................86 
APPENDIX 4. SUMMARY OF CHANGES IN CURRENT PROTOCOL 
AMENDMENT ..........................................................................................................87 
LIST OF TABLES 
Table 1 
TEAEs (System Organ Class ≥10% Subjects) Study GBR 830-101 Part 1 ...............28 
Table 2 
TEAEs (System Organ Class ≥10% Subjects) Study GBR 830-101 Part 2 ...............29 
LIST OF FIGURES 
Figure 1 
Study Design Schematic .............................................................................................33 
Figure 2 
Study Flow Chart ........................................................................................................33 

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1. 
ABBREVIATIONS AND SPECIALIST TERMS 
AD 
Atopic dermatitis 
ADA 
Anti-drug antibodies 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine amino transferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartate amino transferase  
AUC 
Area under the curve 
BAS 
Biological Activity Set 
BMI 
Body mass index 
BP 
Blood pressure 
BSA 
Body surface area 
BUN 
Blood urea nitrogen 
CCL 
Chemokine ligand 
CD 
Cluster of differentiation 
CFR 
Code of Federal Regulations 
Cmax 
Maximum observed plasma concentration 
CPMP 
Committee for Proprietary Medicinal Products 
CRA 
Clinical research associate 
CRF 
Case report form 
CRO 
Contract research organization 
CsA 
Cyclosporine A 
CSR 
Clinical study report 
CTCAE 
Common terminology criteria for adverse events 
DC 
Dendritic cells 
dl 
Deciliters 
DLQI 
Dermatology Life Quality Index 
DPs 
Drug product 
DSM 
Diagnostic and statistical manual 
EASI 
Eczema Area and Severity Index 
ECG 
Electrocardiogram 
eGFR 
Estimated glomerular filtration rate 
ELISA 
Enzyme-linked immunosorbent assay 
FAS 
Full analysis set 
FIH 
First in human 
FSH 
Follicle stimulating hormone  
GCP 
Good clinical practice 
GGT 
Gamma-glutamyl transferase 

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GM-CSF 
Granulocyte-macrophage colony-stimulating factor  
GvHD 
Graft versus host disease 
hARP 
Human acidic ribosomal protein 
Hb 
Hemoglobin 
HBsAg 
Hepatitis B surface antigen 
HCG 
Human chorionic gonadotropin 
HDL 
High-density lipoprotein 
HIV 
Human immunodeficiency virus 
HV 
Healthy volunteers 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International conference on harmonization  
IEC 
Independent ethics committee 
IFN 
Interferons  
Ig 
Immunoglobulin 
IGA 
Investigator’s Global Assessment 
IgE 
Immunoglobulin E 
IHC 
Immuno-histochemistry 
IL 
Interleukin 
IND 
Investigational New Drug 
IP 
Investigational Product 
IRB 
Institutional review board 
IUD 
Intrauterine device 
IUS 
Intrauterine system  
IV 
Intravenous 
IVRS/IWRS Interactive voice response system / Interactive web response system 
KLH 
Keyhole limpet hemocyanin 
LAR 
Legally acceptable representative 
LDL 
Low-density lipoprotein 
LOCF 
Last observation carried forward 
LS 
Lesional skin 
µl 
Microliters 
mAb 
Monoclonal antibody 
MDRD 
Modification of diet in renal disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
Mins 
Minutes 
mL 
Milliliter 
MM 
Medical monitor 
mM 
Millimole 

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mmHg  
Millimeters of mercury 
mRNA  
Messenger ribonucleic acid 
MS 
Multiple sclerosis 
MSD 
Meso Scale Discovery 
msec 
Milli second 
NA 
Not applicable 
NaCl 
Sodium chloride 
NK 
Natural Killer 
NL 
Non-lesional skin 
NOAEL 
No observed adverse effect level 
NRS 
Numerical rating scale 
OX40L 
OX40 ligand 
PBMC 
Peripheral blood mononuclear cell 
PD 
Pharmacodynamic(s) 
PI 
Principal investigator 
PK  
Pharmacokinetics(s) 
PKAS 
Pharmacokinetic analysis set 
QTc 
Corrected QT 
RA 
Rheumatoid arthritis 
RO 
Receptor occupancy 
RT-PCR 
Reverse transcription polymerase chain reaction  
SAE 
Serious adverse event 
SAF 
Safety analysis set 
SAP 
Statistical analysis plan 
SAS 
Statistical analysis system 
SCORAD 
Scoring of Atopic Dermatitis 
SOP 
Standard operating procedure 
sOX40 
Serum soluble OX40 
sOX40L 
Serum soluble OX40 ligand 
t1/2 
Elimination half-life 
TARC 
Thymus and activation-regulated chemokine (CCL17) 
TCS 
Topical corticosteroids 
TEAEs 
Treatment-emergent adverse events 
TEWL 
Transepidermal water loss 
Th1 
Type 1 helper T cell 
Th2 
Type 2 helper T cell 
tmax 
Time at which Cmax is observed 
TNF 
Tumor necrosis factor 
Tregs 
Regulatory T cells 

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TSLP 
Thymic stromal lymphopoietin 
TT 
Tetanus Toxoid  
ULN  
Upper limit of normal 
US 
United states 
VAS 
Visual analogue scale 
VLDL 
Very low-density lipoprotein 
WMA 
World Medical Association 
  
 
 

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2.
PROTOCOL SYNOPSIS
Name of Sponsor/Company: Glenmark Pharmaceuticals SA 
Protocol Title 
A Phase IIa, Double-Blind, Randomized, Placebo-controlled, Exploratory Study to Evaluate the Safety, 
Biological Activity and Pharmacokinetics of GBR 830 in Adult Patients With Moderate-to-Severe Atopic 
Dermatitis 
Protocol Number 
GBR 830-201 
Name of Investigational Product/Code 
GBR 830 
Name of Active Ingredient 
GBR 830 
Phase of Development 
Phase IIa 
Study Rationale 
Inhibition of OX40 has emerged as a novel molecular target from research on the biology and pathophysiology 
that underlie the many facets of inflammation.  Recent studies have shown that OX40 and OX40L play a role in 
the optimal production of T cell cytokines and in regulation of the T-helper (Th) 1/2 balance.  
Atopic Dermatitis (AD) is a chronic inflammatory disease, considered a polar Th2 disease, and chronic AD 
lesions have been shown to have a marked increase in Th2 T cells and related cytokines.  OX40 mediates 
signaling by thymic stromal lymphopoietin (TSLP)-activated dentritic cells (DCs) and is highly upregulated in 
atopic skin.  TSLP-activated DCs have been shown to preferentially activate Th2 T-cell responses in autologous 
and allogeneic cultures in an OX40-dependent manner.   
Data published by Fujita et al, 2011 tested the hypothesis that AD-related DCs induce a Th2-biased immune 
response.  Skin biopsy specimens were collected from patients with chronic AD, psoriasis, and healthy volunteers 
and DC subsets isolated from the lesional skin were analyzed.  OX40L expression was explored in these biopsy 
specimens as a marker of Th2-driving DCs.  A large number of OX40L1 cells were found in AD dermis, with 
minimal expression in psoriatic and normal dermis. 
A study to establish the effect of the systemic immune- suppressant, cyclosporin A (CsA), on AD skin pathology 
was performed by Khattri et al, 2014.  Rapid clinical responses were seen within 2 weeks of CsA treatment, 
associated with strong suppressions of immune and epidermal phenotypes.  AD patients after CsA treatment show 
high inhibition of IL-22, and significant down-regulation of the Th2 axis. 
Recently, a rapid improvement of the AD molecular signature was observed in patients after treatment with 4 
weeks with Dupilumab, a targeted Th2 antagonist.  Dupilumab suppressed mRNA expression of genes related to 
activation of T cells, DCs, eosinophils, inflammatory pathways, and Th2-inducing chemokines in skin lesions, 
with increases or insignificant decreases observed with placebo.  These data suggest that the blockade of key 

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drivers of Th2–mediated inflammation could help in the treatment of AD.  AD is therefore considered a suitable 
model disease for an exploratory signal search study for GBR 830. 
The objective of this study is to explore effects of GBR 830 on biomarkers in AD to generate preliminary clinical 
evidence of biological activity to enable conduct of further definitive efficacy studies in this indication.  
Preliminary safety and pharmacokinetic (PK) data has been generated in a phase I study in healthy volunteers.  
The results of non-clinical pharmacology and toxicology studies conducted with GBR 830 to date supporting this 
study are provided in the Investigator’s Brochure (IB). 
Study Objective(s): 
Primary: 
• 
Safety and tolerability of repeated doses of GBR 830 in adult patients with AD  
• 
Effect of repeated doses of GBR 830 on biomarkers of disease activity in adult patients with AD. 
Secondary: 
• 
Effect of GBR 830 on clinical efficacy parameters in adult patients with AD. 
• 
Pharmacokinetics (PK) of repeated doses of GBR 830 in adult patients with AD. 
• 
Immunogenicity of GBR 830 in adult patients with AD. 
Exploratory : 
• 
Additional exploratory objectives to understand the mechanism of GBR 830 including effect on cellular 
infiltrates and immune pathways 
Study Population 
The target study population is adult males and females with chronic moderate-to-severe AD as defined by 
Eczema Area and Severity Index (EASI) score of ≥ 12; Scoring of Atopic Dermatitis (SCORAD) of ≥ 20; 
Investigator's Global Assessment (IGA) score of ≥ 3 at baseline and with history of inadequate response to topical 
therapies. 
Study Design 
The study is a phase IIa, double-blind, randomized, placebo-controlled, repeated dose study to evaluate safety, 
biological activity and PK of GBR 830 in adult patients with AD.  The study will be conducted in 
approximately16 centers in US/Canada.  The study will be conducted in three phases: screening phase, treatment 
phase and follow-up phase.   
During the screening phase, after providing informed consent, all patients will be screened for eligibility prior to 
inclusion in the study and sufficient number of patients will be screened to ensure approximately 60 to 80 patients 
meeting the eligibility criteria will be randomized.  At screening, patients will be assessed on EASI, IGA, 
SCORAD and BSA rating scales for AD.  Patients will be withdrawn from use of other medication being used to 
control their AD as mentioned in prior and concomitant medication section.  On Day 1, prior to dosing, patients 
will be reassessed on EASI, IGA, SCORAD and BSA rating scales for AD to ensure that they qualify for the 
study. 
A sufficient number of patients will be randomized such that approximately 40 evaluable patients complete at 
least the Day 29 visit.  Approximately 60 to 80 patients are planned to be randomized in a ratio of 3:1 to receive 
GBR 830 (10 mg/kg) or placebo, in a two-arm, parallel design study.   

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Patients who meet eligibility criteria will undergo Day 1/baseline assessments, randomization, and then receive 
the first intravenous (IV) infusion of GBR 830 or placebo.  Each patient will receive two doses of GBR 830 or 
placebo administered 4 weeks apart on Day 1 and Day 29.  Patients will be closely monitored at the study site for 
6 hours after the first infusion (Day 1/baseline) and for 3 hours after the next dose (Day 29).  Patients will return 
for follow-up visits as mentioned in Appendix 1  - schedule of events.  The study site will contact patients by 
telephone approximately 24 hours after each infusion (Days 2 and 30) for concomitant medications and 
procedures, and a general adverse event (AE) query.   
 
Figure 1: Study design 
 
Apart from the dosing visits, patients will be seen in the clinic on Day 4, 8, 15, 22, 29, 32, 36, 43, 50, 57, 71 and 
the end of study visit occurs on Day 85 (week 12) for study assessments and PK sample collection. 
Skin punch biopsy samples for biomarker analysis will be collected at Day 1/baseline, Day 29 and Day 71.  
Analyses will be performed where samples are available.  A gene/mRNA expression profiling will be performed 
to evaluate the effects of OX40 blockade on both lesional and non-lesional skin from patients with AD.  Changes 
in gene expression in the AD transcriptome of lesional skin in comparison to a non-lesional molecular phenotype 
will be used to evaluate treatment-associated effects.  In addition any correlation with improvements in disease 
activity and clinical outcomes will also be evaluated.   
 
Figure 2: Study Flow Chart 
 
 
 
 
Dose 1 
Screening 
Day -30-1 
29 
71 
85 
Dose 2 
1 
 
 
Baseline biopsies 
Repeat biopsies 
 
Repeat biopsies 
  
 
GBR 830 10mg/kg  
Placebo  
N=60 to 80 
randomized 
3:1 (active 
to placebo) 

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Study Endpoint(s) 
Primary: 
• 
All Treatment-emergent adverse events (TEAEs) occurring in the study, in terms of nature, onset, 
duration, severity, relationship and outcome of adverse events (AEs), and serious adverse events (SAEs), 
in adult patients with moderate-to-severe AD. 
• 
Effect of GBR 830 in adult patients with AD in terms of change from baseline in the active AD mRNA 
expression signature and the pathologic epidermal phenotype measures obtained from skin biopsies  
Secondary: 
• 
Proportion of patients who achieve an IGA score of 0 or 1 at each study visit 
• 
Proportion of patients who achieve an EASI 50 and 75 response at each study visit 
• 
Percent improvement in clinical scores EASI, SCORAD, IGA, BSA (Body surface area), Pruritus 
Numerical rating scale (NRS) and Dermatology Life Quality Index (DLQI) from baseline to each visit 
• 
Changes from baseline AD activity as determined by changes in trans-epidermal water loss (TEWL) 
• 
PK of GBR 830 in adult patients with moderate to severe AD in terms of: Cmax, AUC0-tau, AUC0-∞, and 
AUC0-t, t1/2, volume of distribution, clearance and other parameters assessed as relevant after the first 
and last doses 
• 
Anti-drug antibodies (ADA) to GBR 830 to evaluate immunogenicity. 
Exploratory: Change from baseline in levels of: 
• 
Cytokines and chemokines in serum:  IL-22, IL-13, CCL17 (TARC = thymus and activation-regulated 
chemokine), Eotaxin (CCL11), TSLP, CXCL10 (IP-10), CCL2 (MCP-1), CCL20 (MIP3A),CCL22 
(MDC), CCL3 (MIP-1α), CCL4 (MIP-1β), CCL13 (MCP-4), CXCL11 (IP-9; I-TAC), and CXCL9 
(MIG) 
• 
Leukocyte sub-population cell counts (Total T, T helper, Cytotoxic T, Tregs, Memory T cells 
• 
Cellular infiltrates (T-cells, dendritic cells) as assessed by CD3, FcEpsilon RI, OX40L, OX40, and 
MBP. 
• 
Serum total Immunoglobulin E (IgE) serum soluble OX40 (sOX40), serum soluble OX40 ligand 
(sOX40L), and circulating eosinophil counts  
Planned Number of Patients  
Approximately 60 to 80 adult patients with AD are planned to be randomized in a ratio of 3 active:1 placebo, to 
receive either GBR 830 (10 mg/kg) or placebo. 
A sufficient number of patients will be randomized such that approximately 40 evaluable patients complete at 
least the Day 29 visit. 
Planned Duration of Patient Participation 
Screening phase (4 weeks), study duration (12 weeks), total study duration for each patient (16 weeks). 
Inclusion Criteria 
Patients eligible for enrolment in the study must meet all of the following criteria: 

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1. Male or female patients, age ≥ 18 years at the time of informed consent with physician diagnosis of AD 
for > 1 year; diagnosis of AD as defined by the Hanifin and Rajka criteria for AD. 
2. AD involvement of ≥ 10% body surface area (BSA) prior to randomization  
3. EASI score of ≥ 12 prior to randomization; SCORAD of ≥ 20 prior to randomization; baseline IGA 
score of ≥ 3 prior to randomization; and history of inadequate response to a stable (> 1 month) regimen 
of class 3 or higher strength topical corticosteroids (TCS), or calcineurin inhibitors or for whom topical 
treatments are otherwise inadvisable (e.g., because of important side effects or safety risks) (Refer to 
Section 9.1 for details) 
4. Patient’s body mass index (BMI) should be within the range 18.5–35 kg/m2 (inclusive); weight must be 
> 50 kg. 
5. Patients deemed fit to receive the study medication, as determined by medical history, vital signs, 
physical examinations, Electrocardiograms (ECG), laboratory studies, and other tests performed within 
30 days prior to drug administration, as judged by the Investigator. 
6. Patients must agree to the following requirements during the study: 
a. 
Women of child-bearing potential and men with partners of child-bearing potential must ensure 
that two effective means of contraception are used, by them and/or their partners, for the period 
between signing of informed consent and a minimum of 180 days after the last dose of study 
drug. 
Acceptable forms of effective contraception include: 
• 
Established use of oral, injected, or implanted hormonal methods of contraception. 
• 
Tubal ligation. 
• 
Placement of an intrauterine device (IUD) or intrauterine system (IUS). 
• 
Barrier methods only when used consistently with spermicidal foam/gel/film/cream or 
suppository.  Acceptable barrier methods include the following: 
i. 
Male or female condom. 
ii. 
Occlusive cap (diaphragm or cervical/vault caps). 
• 
Male sterilization (with post-vasectomy documentation of the absence of sperm in the 
ejaculate) (For female patients on the study, the vasectomized male partner should be the 
sole partner for that patient).  If a subject cannot provide written documentation of male 
sterilization, a verbal statement from the subject will suffice. 
• 
Maintenance of abstinence when this is in line with the preferred and usual lifestyle of the 
patient (i.e., not periodic abstinence, such as during ovulation) judged reliable by the 
Investigator. 
Patients in relation with a same-sex partner do not need to use contraception, if he/she is the 
sole partner for that patient) 
Of the acceptable forms of effective contraception, at least one method needs to be a barrier 
method. 

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b. Male patients should agree not to donate sperm until 180 days after administration of the last 
dose of the study medication.  Female patients should not donate eggs for 180 days following 
investigational product administration. 
c. 
All female patients must be non-pregnant and non-lactating and test negative for pregnancy at 
the time of screening and prior to randomization. 
7. Female patients of non-child-bearing potential (i.e., are postmenopausal or permanently sterilized 
[bilateral oophorectomy, hysterectomy, bilateral salpingectomy]).  Such patients will not be required to 
use contraception.   Postmenopausal is defined as at least 1 year post cessation of menses (without an 
alternative medical cause) with follicle stimulating hormone (FSH) ≥ 40.0 mIU/mL. 
8. Provide written informed consent 
9. Willing and able to comply with all aspects of the protocol including willingness to undergo 4 on study 
skin biopsies 
Exclusion Criteria 
Patients meeting any of the following criteria must not be enrolled in the study:    
1. Patients with a history of drug or other allergy considered clinically significant in the opinion of the 
Investigator, which contraindicates participation or a previous history of hypersensitivity to murine 
proteins. 
2. Patients who have had a live vaccination within 12 weeks before randomization, or intend to have a live 
vaccination during the course of the study, or have participated in a vaccine clinical trial within 12 
weeks prior to randomization 
3. History of a serious local infection, systemic infection, or gastrointestinal infection within 12 weeks of 
baseline; infections requiring systemic antibiotic/ anti-viral/ anti-parasitic/ anti-fungals within 4 weeks 
of baseline; evidence of clinically significant active infection, or fever ≥38.0oC (100.4oF) within one 
week of randomization.. 
4. Patients who have evidence of active or latent tuberculosis as documented medical history, or test 
positive for QuantiFERON Gold Blood TB Test 
5. Patients with evidence of skin conditions at screening that would interfere with evaluations of the study 
drug 
6. Treatment with systemic corticosteroids within 4 weeks before randomization, and topical 
steroids/tacrolimus and or/pimecrolimus within 1 week before the randomization (except emollients, and 
mild steroids (class 6 or 7) 
7. Treatment with systemic therapy for AD (such as psoralen and ultraviolet A light therapy, cyclosporine, 
methotrexate, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, azathioprine), or 
phototherapy (including ultraviolet B or self-treatment with tanning beds or therapeutic sunbathing) 
within the 4 weeks before randomization or other drugs with potential for immunosuppression such as 
cytotoxic agents or cyclophosphamide taken within 4 weeks prior to randomization. 
8. Any cell-depleting agents including but not limited to rituximab: within 6 months prior to the baseline 
visit, or until lymphocyte and CD 19+ lymphocyte counts return to normal, whichever is longer. 
Other biologics: within 5 half-lives or 8 weeks prior to the baseline visit, whichever is longer.  Allergen 
immunotherapy within 6 months before the baseline visit. 

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9. Patients who are immunocompromised, have had a recent (within 3 months before randomization) or 
current serious systemic or local infection (including infectious mononucleosis-like illness or herpes 
zoster) suggestive of immunocompromise. 
10. Patients who have current or a history of lymphoproliferative disease or history of malignant disease; or 
signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or 
splenomegaly; or active primary or recurrent malignant disease. 
11. Patients with history or presence of other inflammatory or auto-immune disease or rheumatological or 
joint diseases other than AD. 
12. History of parasitic infections within 1 year before randomization. 
13. History of alcohol or drug abuse or dependence within 2 years of the screening visit. 
14. Patients with a positive result from the drug and alcohol screen. 
15.  Patients who test positive for disease markers of Human immunodeficiency virus (HIV), Hepatitis B or 
Hepatitis C. 
16. Patients with an abnormal ECG (including a QTc >450 msec for men, >460 msec for women) 
considered clinically significant in the opinion of the Investigator at screening and/or prior to 
randomization (QTc calculated based on Fridericia’s formula). 
17. Patients with lab values, which are significantly different from normal reference ranges (as defined in 
Appendix 2) and/or judged clinically significant by the Investigator, including but not limited to: 
a. 
Patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 as determined by 
the modification of diet in renal disease (MDRD) method. 
b. Alanine amino transferase (ALT) or Aspartate amino transferase (AST) ≥2.5 times upper limit 
of normal (ULN), and/or serum total bilirubin ≥1.5 times ULN, at screening. 
c. 
Hemoglobin (Hb) value less than 9 g/dL at screening. 
d. Absolute neutrophil count ≤1,500/µL or absolute lymphocyte count ≤800/μL or platelet count 
≤150,000/µL or any abnormal evaluations judged clinically significant by the Investigator at 
screening and prior to randomization. 
18. Patients with any evidence of organ dysfunction or any clinically significant medical history or findings 
in physical examinations or investigations or has a clinical condition or receiving therapy that, in the 
opinion of the Investigator, would make the patients unsuitable for study.  
19. Patients with a history of current or previous psychiatric illnesses or previous psychiatric events that 
would either put the patient at undue risk or interfere with study procedures according to the 
investigator. 
20. Treatment with an investigational drug within 8 weeks or within 5 half-lives, if known (whichever is 
longer), before the baseline visit. 
Study-Specific Discontinuation/Withdrawal Criteria  
• 
Withdrawal of consent by the patient to continue in the study. 
• 
Development of a serious or intolerable AE that necessitates discontinuation at the discretion of 
the Investigator. 

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• 
At the discretion of the Investigator, when he/she believes continued participation is not in the 
best interest of the patient. 
• 
At the discretion of the Investigator, when he/she believes the patient has not adhered to the 
study procedures or restrictions. 
• 
A positive pregnancy test. 
• 
Protocol deviation that, in the opinion of the Sponsor and Investigator, warrants discontinuation 
from the study 
• 
A patient requires concomitant medications, which may interfere with the PK of the study drug.  
Note: withdrawal in such cases will be discussed and mutually agreed by the Investigator and 
the Sponsor. 
• 
Patients requiring rescue medications or interventions 
• 
The patient for any reason requires treatment with another therapeutic agent that has been 
demonstrated to be effective for the treatment of AD.  In this case, discontinuation from the 
study should occur prior to introduction of the new agent. 
• 
Disease progression/exacerbation, which in the opinion of the Investigator would require 
interruption of treatment or premature termination of follow up.   
• 
Patients randomized in the study who withdraw their consent for the first post-baseline skin 
biopsies. 
All efforts will be made to monitor the patients withdrawn during the study for safety and PK analysis, 
throughout the duration of study. 
The decision to discontinue dosing in a patient due to adverse drug effects will be made on the basis of clinical 
severity and relatedness to study drug.  Except in cases of emergency, it is recommended that the Investigator 
consult the medical monitor (MM) before removing the patient from the study. 
Lifestyle and/or Dietary Restrictions 
Women of child-bearing potential and men with partners of child-bearing capacity must ensure that two highly 
effective means of contraception are used, by them and/or their partners, for the period between signing of 
informed consent and a minimum of 180 days after dosing. 
Name of Investigational Product: GBR 830  
Dosage Form: Solution for IV infusion.  
Dosage: 10 mg/kg 
Dosage Frequency: Two doses administered at an interval of once every 4 weeks 
Mode of Administration: GBR 830 will be diluted in normal saline and administered as IV infusion over 60 
mins.  
 
Placebo/Control/Comparator  
Name of Placebo/Control/Comparator: Placebo (formulation buffer) 
Dosage Form: Solution for IV infusion  

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Dosage: NA 
Dosage Frequency: Two doses administered at an interval of once every 4 weeks 
Mode of Administration: Placebo will be diluted in normal saline and administered as IV infusion over 60 mins. 
Duration of Treatment  
Two doses of study drug given four weeks apart. 
Prohibited Prior and Concomitant Drug/Therapy 
Prior Medication: 
• 
Treatment with systemic corticosteroids within 4 weeks before randomization, and topical steroids/ 
tacrolimus and/or pimecrolimus within 1 week prior to randomization except emollients, and mild 
steroids (class 6 or 7), applied other than on target area that will be the site for the skin biopsies. Nasal 
and inhaled corticosteroids use is allowed during study. 
• 
Treatment with systemic therapy for AD (such as psoralen and ultraviolet-A  light therapy, cyclosporine, 
methotrexate, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, azathioprine), or 
phototherapy (including ultraviolet B or self-treatment with tanning beds or therapeutic sunbathing) 
within 4 weeks before randomization 
• 
Other drugs with potential for immunosuppression such as cytotoxic agents or cyclophosphamide taken 
within 4 weeks prior to randomization.  
• 
Previous use of biological mAb therapies within 3 months or five half-lives (whichever is longer) of the 
drug prior to randomization or have previously used biological therapies or allergen immunotherapy for 
the treatment of AD. 
• 
Complementary or alternate therapies for the treatment of AD/inflammatory conditions.  However 
patients can be included subsequent to an adequate wash-out period (14 days or five half-lives of the 
complementary or alternate therapy prior to randomization, whichever is longer). 
Concomitant Medication: 
• 
All restrictions on the medications listed above in the “prior medication” are applicable for the entire 
duration of the study  
Other concomitant medications that the patient receives on a regular basis may continue if in the opinion of the 
investigator it does not put the patient at undue risk or nor interfere with the study evaluations.  Patients should be 
stable on allowed concomitant medication for at least 3 months prior to study.  All concomitant medications taken 
by the patient shall also be recorded in the patient diary and Prior & Concomitant Medication Forms of electronic 
case record form (eCRF). 
Assessments 
Pharmacokinetic, Pharmacodynamic, Biomarker, and Pharmacogenomic Assessments 
Pharmacokinetic Assessments 
Blood samples will be obtained at appropriate time points defined in Appendix 1.  Concentrations of GBR 830 in 
serum will be measured at defined time points. 
Pharmacokinetic parameters including Cmax, AUC0-tau, AUC0-∞, and AUC0-t, t1/2, Tmax, clearance, volume of 
distribution, and other related PK parameters will be evaluated as relevant.   

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Biomarker Assessments 
Gene expression profiling of AD transcriptome: Skin punch biopsy samples for biomarker analysis will be 
collected at Day 1/baseline, Day 29 and Day 71.  Analyses will be performed where samples are available.  
Changes in gene expression in the AD transcriptome of lesional skin (LS) in comparison to a non-lesional (NL) 
molecular phenotype will be used to evaluate treatment-associated effects.  The improvement in the AD 
transcriptome of LS will be defined as treatment-associated changes in gene expression toward a NL molecular 
phenotype.  A ‘‘worsening’’ or exacerbation will be defined as gene expression changes further distinguishing 
LSs from NLs. 
In addition, skin biopsy samples will be evaluated for routine histopathology for evaluation of disease severity.   
Leukocyte sub-population cell counts, cytokines, chemokines, TEWL, total IgE, sOX40L, and eosinophil levels 
will also be measured in the study.  Cellular infiltrates (T-cells, dendritic cells) will be assessed by 
immunohistochemistry of biopsy slides with CD3, FcEpsilon RI, OX40L, OX40, and MBP. 
Serum soluble OX40 and OX40L will be measured using PK samples at the time points defined in Appendix 1. 
Safety Assessments 
Safety and tolerability of GBR 830 including AEs, SAEs, vital signs, laboratory parameters, ECGs, and physical 
examinations.  
Efficacy Assessments 
• 
The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent 
of AD.  Four AD disease characteristics will be assessed for severity by the Investigator or designee on a 
scale of “0” (absent) through “3” (severe).  In addition, the area of AD involvement will be assessed as a 
percentage by body area of head, trunk, arms, and legs and converted to a score of 0 to 6. 
• 
The SCORAD is a validated tool used in clinical research and clinical practice that was developed to 
standardize the evaluation of the extent and severity of AD.  The extent of AD is assessed as a percentage of 
each defined body area and reported as the sum of all areas, with a maximum score of 100% (assigned as “A” 
in the overall SCORAD calculation).  The severity of 6 specific symptoms of AD is assessed using the 
following scale: none (0), mild (1), moderate (2), or severe (3) (for a maximum of 18 total points, assigned as 
“B” in the overall SCORAD calculation).  Subjective assessment of itch and sleeplessness is recorded for 
each symptom by the patient or relative on a visual analogue scale (VAS), where 0 is no itch (or 
sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), with a maximum possible score of 20.  
This parameter is assigned as “C” in the overall SCORAD calculation.  The SCORAD is calculated as: A/5 + 
7B/2 + C.  
• 
The IGA is an assessment scale used in clinical studies to determine severity of AD and clinical response to 
treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe/very severe). 
• 
Pruritus Numerical rating scale (NRS): Patients will record once daily and respond to the following question, 
“On a scale of 0 – 10, with 0 being “no itch” and 10 being the “worst itch imaginable”, how would you rate 
your worst degree of itch during the previous 24 hours?” Patient compliance on the pruritus NRS will be 
followed at each clinic visit. 
• 
Dermatology Life Quality Index (DLQI): The DLQI is a simple, patient-administered, 10-question, validated, 
quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, 
work and school, personal relationships, and treatment.  Response categories include “a little,” “a lot,” and 
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scored as “0.” Totals range from 0 to 30 (less to more impairment) and a 5–point change from baseline is 
considered clinically relevant. 
Immunogenicity: 
Blood samples will be obtained at appropriate time points for immunogenicity assessment as defined in 
Appendix 1.  Overall ADA incidence of the study along with patient ADA status and titers for positive confirmed 
sample will be reported. 
Bioanalytical Methods 
Validated bio-analytical methods will be used for quantification of serum GBR 830, and for detection and 
confirmation of anti- GBR 830 antibodies and neutralizing antibodies. 
Statistical Methods  
Determination of Sample Size  
No formal sample size calculation will be performed for this study.  The sample size chosen is based on 
experience from previous studies of similar nature.  Patients, who are permanently discontinued from study drug 
due to reasons other than an AE and before the first post baseline skin biopsies or before receiving two doses of 
study drug, will not be considered evaluable for the Biological Analysis Set (see Section 13.2).  The sample size 
of 60 to 80 adult patients with AD randomized in ratio of 3:1 (GBR 830 vs placebo), with approximately 40 
evaluable patients, is considered to be sufficient to provide descriptive information on the PK, safety, tolerability 
and potential efficacy of GBR 830. 
A patient will be considered evaluable if he/she completes the Day 29 visit and has at least one post-baseline skin 
biopsy (Visit 7) and received two doses of study drug (Visit 7). 
Efficacy Analyses 
Analysis of Primary Efficacy Endpoint(s) 
Other than safety, the primary endpoint will be absolute change from baseline in the active AD mRNA expression 
signature.  Details of analysis will be specified in the SAP. 
Analysis of Secondary Efficacy Endpoint(s) 
The statistical methods, including methods for the handling of missing data, for analyzing the secondary 
endpoints will be fully described in the Statistical Analysis Plan (SAP). 
Pharmacokinetic, Pharmacodynamic, Pharmacogenomic, and Other Biomarker Analyses 
Pharmacokinetic Analyses 
PK parameters will be summarized in tabular and graphic form.  Results of exploratory analyses will be 
summarized.  Details of PK analysis will be specified in the SAP. 
Pharmacodynamic, Pharmacogenomic, and Other Biomarker Analyses 
PD parameters will be summarized in tabular and graphic form.  Results of exploratory analyses will be 
summarized. 
Details of exploratory analyses to be performed will be specified in the SAP.  

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Safety Analyses 
Adverse events will be summarized by system organ class, preferred term and treatment group. Patients will be 
counted only once for each preferred term, system organ class, and by the highest severity of an event.  Vitals, 
physical examinations and ECG evaluations will be summarized with descriptive statistics.  Laboratory 
evaluations will be summarized with descriptive statistics at each visit, and change from baseline summarized for 
each post-baseline visit.  Laboratory measurements will also be summarized based on the number and percentage 
of patients above or below a pre-specified threshold for each test.  Details will be presented in the SAP. 
Interim Analyses 
No interim analysis is planned. 
 
 
 

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3. 
INVESTIGATOR’S SIGNATURE  
• I have reviewed the clinical protocol.  
• I have fully discussed the objective(s) of this study and the contents of this protocol 
with the Sponsor’s representative.  
• I understand that the information in this protocol is confidential and should not be 
disclosed, other than to those directly involved in the execution or the 
scientific/ethical review of the study, without written authorization from the Sponsor.  
It is, however, permissible to provide the information contained herein to a patient in 
order to obtain their consent to participate.   
• I agree to conduct this study according to this protocol and to comply with its 
requirements, patient to ethical and safety considerations and guidelines, and to 
conduct the study in accordance with International Conference on Harmonization 
(ICH) guidelines on Good Clinical Practice (GCP) and with the applicable regulatory 
requirements.   
• I understand that failure to comply with the requirements of the protocol may lead to 
my participation as an Investigator for this study to be terminated.   
• I understand that the Sponsor may decide to suspend or prematurely terminate the 
study at any time for whatever reason; such a decision will be communicated to me in 
writing.  Conversely, should I decide to withdraw from execution of the study I will 
communicate my intention immediately in writing to the Sponsor.  
 
_________________________________ 
___________________ 
Name of Investigator, degree: 
 
Date 
Title: 
 
 
Address and contact details: 
 
 
 
 

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5. 
BACKGROUND INFORMATION 
5.1. 
Introduction 
Allergy and autoimmune diseases affect more than 5-10% of the human population (Cooper et 
al, 2003) and are associated with high morbidity and mortality.  They are chronic debilitating 
diseases that often attack young adults, especially women, and their social and economic impact 
is enormous.  The limitations of currently available therapies are the slow onset of action, 
moderate efficacy that declines after several years of treatment, and side effects, the most 
common being hepatotoxicity, myelosuppression and/or general immunosuppression. 
The introduction of biological therapies in the late nineties opened a new era in the treatment of 
autoimmunity, and exerted a significant impact on the disease course and the quality of life of 
patients.  There are several biologicals that are either approved or in advanced clinical trials, the 
vast majority of which are used in the treatment of in rheumatoid arthritis (RA), multiple 
sclerosis (MS) and/or Crohn’s disease (Balague et al, 2009). 
AD is one of the most prevalent disorders worldwide that affects 4%-7% of adults and 15-25% 
of children with a significant impact on quality of life of patients.  It is a chronic, relapsing 
inflammatory skin disease characterized by intense pruritus (e.g., itchiness) and by scaly and dry 
eczematous lesions and often associated with other atopic disorders, such as allergic rhinitis and 
asthma.   
Despite its increasing prevalence worldwide, and the burden on society, specific therapies for 
AD are still limited, and most commonly used therapies are not based on current mechanistic 
understanding of the disease.  Approximately 20% of patients with AD have moderate to severe 
disease and generally require systemic therapy, as outlined in several international and regional 
treatment guidelines (Sidbury et al, 2014, Ring et al, 2012).  Most traditional therapies are 
intended for clinical improvement and symptomatic relief without targeting the specific 
pathways that initiate and promote AD. 
Recent findings link immune and epidermal barrier defects in AD (Raap et al, 2012; Szegedi et 
al, 2012), suggesting that disease-driving Th2 cytokines involved in AD, such as IL-4, IL-13 and 
IL-22 inhibit production of barrier proteins (i.e filaggrin and loricrin) and antimicrobial peptides.  
Thus, inhibition of specific adaptive immune responses or cytokine pathways would be expected 
to lead to skin barrier repair.  Antagonism of this polarized T-cell pathway has the potential to 
produce fewer immune antagonism related adverse effects, unlike the multiple adverse effects 
with broad T-cell suppression. 
Although there are multiple systemic agents recommended for the treatment of AD, many of the 
patients still do not achieve optimal efficacy and these treatments have limited efficacy in 
moderate to severe disease.  Drug-specific major safety concerns are another major limitation 
(Levin et al, 2014).  Thus, there remains a significant unmet patient need for new agents with 
unique mechanisms that can provide improved and sustained skin clearance, and a safety profile 

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that allows for chronic use.  Biologic agents hold the promise for a more targeted, effective and 
less toxic approach to systemic therapy.   
5.2. 
Investigational Product: Mechanism of Action 
GBR 830 is a highly selective, humanized monoclonal antibody (mAb) of the IgG1 subtype 
which targets the human OX40 receptor; a member of the tumor necrosis factor receptor 
(TNF-R) gene family.  A common function of TNF-R family members is the regulation of 
T cell-mediated activation and/or apoptosis.  OX40 appears to be an excellent target for 
autoimmune therapy because the T cells that express OX40 are highly enriched for the cells that 
react with auto-antigen at the site of inflammation.  These molecules strongly regulate 
conventional cluster of differentiation (CD) 4 and CD8 T cells.  More recent data have 
demonstrated their ability to modulate Natural killer (NK) T cell and NK cell function as well as 
to mediate cross-talk with professional antigen-presenting cells and diverse cell types such as 
mast cells, smooth muscle cells, and endothelial cells.  Additionally, OX40-OX40L interactions 
alter the differentiation and activity of regulatory T cells (Croft, 2010).  
Blocking the OX40/OX40L pathway has been shown to be protective in several animal models 
of human disease such as asthma, irritable bowel disease, transplant rejection, autoimmune 
diabetes, graft versus host disease (GvHD), and experimental autoimmune encephalomyelitis, 
thus validating OX40 as a highly attractive pathway to antagonize in autoimmune diseases.  
Unlike conventional immunotherapies, blockade of OX40–OX40L interactions seems to inhibit 
disease-responsible effector T-cell function specifically, and therefore not cause widespread 
immunosuppression. 
5.3. 
Preclinical Experience 
Functional pharmacology studies have demonstrated that GBR 830 is able to block the 
interaction between OX40 and OX40L and suppress T cell proliferation and allogeneic reactions, 
such as mixed lymphocyte reactions, with 50% effective concentrations ranging from 0.1 to 
3 µg/mL.  These studies have also demonstrated that GBR 830 has antibody-dependent cellular 
cytotoxicity and complement-dependent cytotoxicity potential.  Consistent with in vitro data, in 
vivo pharmacology studies demonstrated that GBR 830 could suppress a xenogeneic reaction in 
a human-mouse GvHD model at doses as low as 1 mg/kg.  Studies using a human psoriatic skin 
transplant model have demonstrated the potent therapeutic anti-psoriatic activity of GBR 830. 
Secondary pharmacodynamics studies were conducted to support the safety of GBR 830 
administration in humans.  GBR 830 was devoid of agonistic potential and did not induce 
cytokine release in either human peripheral whole blood from healthy volunteers or human 
peripheral blood mononuclear cell (PBMC) cultures at high density.  Taken together, these 
studies suggest a low risk of inadvertent cytokine release in humans for GBR 830. 
In-vitro vaccine reactivation assays suggest that targeting pathological responses driven by 
memory T cell reactivation with GBR 830 is relevant and potentially more efficacious than 
blocking CD28 signals.  In-vivo studies, conducted to evaluate the effect of GBR 830 treatment 

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on a T-dependent antibody response to keyhole limpet hemocyanin (KLH), suggest that targeting 
OX40 has more profound effects on late and memory responses than primary responses.  This 
feature highlights that an antagonistic OX40 treatment in the clinic may display a safer profile in 
terms of infection susceptibility compared with broader immunosuppressors. 
In vivo efficacy of GBR 830 has been demonstrated in an acute GvHD model (mainly 
prophylactic) and in a human psoriasis xenograft (therapeutic) model.  The efficacy in these 
studies was observed to be similar to or better than that observed with established drugs 
(efalizumab, etanercept, temovate, cyclosporin).  These data confirm the immunomodulatory 
capabilities of GBR 830 in T cell mediated autoimmune and inflammatory conditions. 
Administration of GBR 830 to cynomolgus monkeys at doses up to 100 mg/kg/week for 6 weeks 
showed no adverse treatment-related changes in any of the evaluated parameters.  The no 
observed adverse effect level (NOAEL) was 100 mg/kg/week. 
5.4. 
Clinical Experience 
A Phase I study, entitled “A Two-Part, Phase I, Randomized, Placebo-controlled, Single 
Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GBR 830 in 
Adult Healthy Volunteers (Part 1) and a Randomized, Placebo-controlled, Pharmacodynamic 
Study to Evaluate the Effects of a Single Dose of GBR 830 on the Vaccination Response in 
Adult, Healthy Volunteers (Part 2),” was conducted to evaluate the safety, PK and PD of GBR 
830 in healthy volunteers (GBR 830-101).  All subjects completed the study as planned and 
safety data from this study suggest that single IV doses of GBR 830 are safe and well tolerated 
up to 10 mg/kg administered over 1 hour.   
In Part 1 of the study, sequential doses of 0.3, 1.0, 3.0, and 10 mg/kg were evaluated in cohorts 
of 8 subjects each (n=6 GBR 830, n=2 placebo/cohort) to determine the safety and 
pharmacokinetics of single IV doses of GBR 830 in adult healthy volunteers.  Immunogenicity 
was also determined.  To fully characterize the safety and PK profile, subjects were evaluated for 
adverse events, changes in vital signs, ECGs, physical examinations, clinical laboratory test 
results (including hematology, biochemistry, urinalysis), cytokine analysis (IL-1β, IL-2, IL-6, 
IL-8, IL-10, IL-12 p70, TNFα, Granulocyte-macrophage colony-stimulating factor (GM-CSF), 
and Interferon (IFN) γ), and flow cytometry (immunophenotyping), relative to baseline and 
placebo treatment for 10 weeks post dose. 
Part 2 of the study evaluated the effect of a one hour infusion of 10 mg/kg dose of GBR 830 
(n=10 GBR 830 and n=10 placebo) on vaccination response (e.g., the T cell dependent primary 
[naïve] antibody response to neo-antigen KLH and T cell dependent recall/memory antibody 
response to Tetanus Toxoid [TT] antigen) in 20 healthy volunteers.  In addition, safety, PK, and 
immunogenicity of a single IV dose of GBR 830 were evaluated for up to 10 weeks. 

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5.4.1. 
Summary of Safety 
In the GBR 830-101 study, 52 healthy male and female subjects were randomized to either 
GBR 830 (n=34) or placebo (n=18).  A total of 51 subjects completed the study per protocol; one 
subject withdrew consent for personal reasons (not related to AEs). 
In Part 1 of the study, 47 treatment-emergent adverse events (TEAEs) were reported by 69% (22) 
of all the subjects (63% of the placebo subjects and 71% of the GBR 830 subjects) (Table 1).  
Except for 2 events of tooth abscess of moderate intensity, all other TEAEs were mild.  All 
TEAEs had recovered by the time of the last follow-up visit except for 3 TEAEs of mild 
intensity, not related to study drug, for which the outcomes were either unknown (myalgia) or 
still present (pain in extremity, muscle twitching).   
Table 1 
TEAEs (System Organ Class ≥10% Subjects) Study GBR 830-101 Part 1 
System organ class 
GBR 830 (n=24) 
Placebo (n=8) 
Any TEAE 
17 (71%) 
5 (63%) 
General Disorders and Administration Site 
Conditions 
7 (29%) 
2 (25%) 
Nervous System Disorders 
6 (25%) 
3 (38%) 
Infections and Infestations 
3 (13%) 
1 (13%) 
There was no relationship between dose, including placebo, and frequency of TEAEs.  The 
percentage of placebo subjects reporting TEAEs (63%) was within the range reported by subjects 
who received GBR 830 (50% to 83%).  None of the 47 TEAEs in Part 1 was considered related 
to study drug. 
In Part 2 of the study, 34 TEAEs were reported by 65% (13) of all the subjects (80% placebo 
subjects and 50% GBR 830 subjects) (Table 2).  The majority of these TEAEs were mild; only 
5 TEAEs were of moderate intensity (influenza-like illness in one placebo subject and 
influenza-like illness, postural dizziness, pyrexia, and vomiting [all in one GBR 830 subject 
each]).  All TEAEs were resolved by end of the study except for a cough in one subject 
(GBR 830) (Table 2). 

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Table 2 
TEAEs (System Organ Class ≥10% Subjects) Study GBR 830-101 Part 2 
System organ class 
GBR 830 (n=10) 
Placebo (n=10) 
Any TEAE 
5 (50%) 
8 (80%) 
General Disorders and Administration Site 
Conditions 
2 (20%) 
3 (30%) 
Gastrointestinal Disorders 
3 (30%) 
1 (10%) 
Nervous System Disorders 
3 (30%) 
3 (30%) 
Infections and Infestations 
1 (10%) 
1 (10%) 
Musculoskeletal and Connective Tissue Disorders 
2 (20%) 
3 (30%) 
Vascular Disorders 
2 (20%) 
0 (0%) 
Two TEAEs (headache and nausea) in Part 2 were considered by the Investigator to be related to 
placebo. 
There were no deaths, SAEs, or withdrawals due to AEs during the study. 
There were no clinically significant findings with respect to clinical laboratory, vital signs, ECG, 
physical examination or cytokines in any of the subjects in Part 1 and Part 2.  Details of study are 
presented in the IB. 
5.5. 
Study Rationale 
Inhibition of OX40 has emerged as a novel molecular target from research on the biology and 
pathophysiology that underlie the many facets of inflammation.  Recent studies have shown that 
OX40 and OX40L play a role in the optimal production of T cell cytokines and in regulation of 
the T-helper (Th) 1/2 balance.   
AD is a chronic inflammatory disease in which skin lesions show a marked increase in Th2 cells, 
Type 22 (T22) cells, and related cytokines i.e., interleukins-4 (IL-4), -5, -6, -9, -10, -13, and -22  
(Guttman-Yassky et al, 2007; Guttman-Yassky et al, 2011; Croft, 2010).  The OX40 ⁄OX40L 
interaction has been suggested to play an essential role in the pathogenesis of AD.  OX40L is 
expressed by APCs, endothelial cells and T cells, whereas OX40 is found mainly on activated T 
cells.  The expression of OX40L on dendritic cells (DC) is induced by TSLP and TSLP-activated 
DCs migrate into lymph nodes where OX40 ⁄OX40L interaction triggers the differentiation of 
inflammatory Th2 cells that produce IL-4, IL-5, IL-13 and TNF-a, but no or only little IL-10.  
Thymic stromal lymphopoietin (TSLP)-activated dentritic cells (DCs) are highly upregulated in 
atopic skin.  TSLP-activated DCs have been shown to preferentially activate Th2 T-cell 
responses in autologous and allogeneic cultures in an OX40-dependent manner.  The finding that 
OX40/OX40L interactions are the molecular trigger responsible for the induction and 
maintenance of TH2 responses by TSLP-activated DCs provides a plausible molecular 
explanation for initiation and maintenance of allergic diseases.  These exciting findings suggest 
that inhibition of OX40 provides a novel therapeutic approach for the treatments of allergic 
diseases. 

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Data published by Fujita et al, 2011 tested the hypothesis that AD-related DCs induce a 
Th2-biased immune response.  Skin biopsy specimens were collected from patients with chronic 
AD, psoriasis, and healthy volunteers and DC subsets isolated from the lesional skin were 
analyzed.  OX40L expression was explored in these biopsy specimens as a marker of Th2-
driving DCs.  A large number of OX40L1 cells were found in AD dermis, with minimal 
expression in psoriatic and normal dermis. 
A study to establish the effect of the systemic immune- suppressant, cyclosporin A (CsA), on 
AD skin pathology was performed by Khattri et al, 2014.  Rapid clinical responses were seen 
within 2 weeks of CsA treatment, associated with strong suppressions of immune and epidermal 
phenotypes.  AD patients after CsA treatment show high inhibition of IL-22, and significant 
down-regulation of the Th2 axis. 
Recently, a rapid improvement of the AD molecular signature was observed in patients after 
treatment with 4 weeks with Dupilumab, a targeted Th2 antagonist.  Dupilumab suppressed 
mRNA expression of genes related to activation of T cells, DCs, eosinophils, inflammatory 
pathways, and Th2-inducing chemokines in skin lesions, with increases or insignificant 
decreases observed with placebo.  These data suggest that the blockade of key drivers of Th2–
mediated inflammation could help in the treatment of AD.  AD is therefore considered a suitable 
model disease for an exploratory signal search study for GBR 830. 
The objective of this study is to explore effects of GBR 830 on biomarkers in AD to generate 
preliminary clinical evidence of biological activity to enable conduct of further definitive 
efficacy studies in this indication.  Preliminary safety and PK data has been generated in a phase 
I study in healthy volunteers.  The results of non-clinical pharmacology and toxicology studies 
conducted with GBR 830 to date supporting this study are provided in the IB. 
5.6. 
Benefit-Risk Assessment 
GBR 830 is a mAb against OX40 (CD134), a co-stimulatory receptor present on activated T cells 
responsible for the expansion and maintenance of effector and memory immune responses.  
Blocking the binding of OX40 to its ligand, OX40L (CD252) reduces the longevity and efficacy 
of these immune responses.  GBR 830 is thus being developed to treat a broad range of 
autoimmune disorders.  Glenmark has recently completed a phase I first in human (FIH) study 
with GBR 830 in the Netherlands and now intends to submit an Investigational New Drug (IND) 
application for an exploratory Signal Search Study in patients with moderate to severe AD.   
Extensive preclinical functional characterization studies have been conducted with GBR 830 to 
validate the mechanism of action (Details in the IB).  The findings from these studies are in 
agreement with the expected pharmacological effect of an antagonist anti-OX40 antibody. 
Secondary pharmacodynamics studies were conducted to support the safety of GBR 830 
administration in humans (Details in the IB).  GBR 830 was devoid of agonistic potential and did 
not induce cytokine release in either human peripheral whole blood from healthy volunteers or 
human peripheral blood mononuclear cell (PBMC) cultures at high density.  These studies 
suggest a low risk of inadvertent cytokine release in humans for GBR 830. 

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GBR 830 has been administered to cynomolgus monkeys in a 6 week repeat dose toxicology 
study (Details in the IB).  Administration of GBR 830 at doses up to 100 mg/kg/week for 6 
weeks showed no adverse treatment-related changes in any of the parameters.  The no observed 
adverse effect level (NOAEL) was 100 mg/kg/week.  Based on these data, GBR 830 was 
considered to have an acceptable safety profile for the phase I clinical study in healthy adult 
human volunteers.   
A two-part, first-in-human, single ascending dose, phase I study of GBR 830 in healthy 
volunteers (HVs) recently completed.  Review of safety data from both Part 1 and Part 2 of this 
study suggests that GBR 830 is safe and well tolerated.  There were no SAEs and almost all AEs 
were considered by the investigator to be unrelated to the study drugs.  There were no clinically 
meaningful trends in clinical laboratory evaluations, vital signs, ECGs, or physical examination 
findings. 
The safety profile from the phase I study supports further development of GBR 830.  
Urgent Safety Measures 
The Sponsor and Investigator may take appropriate urgent safety measures in order to protect the 
patients of a clinical trial against any immediate hazard to their health or safety.  If such 
measures are taken by Contract research organization (CRO) on behalf of the Sponsor, they shall 
immediately (no later than three days from the date the measures are taken) give written notice to 
the licensing authority and the relevant ethics committee of the measures taken and the 
circumstances giving rise to those measures.   
6. 
STUDY OBJECTIVE(S) 
6.1. 
Primary Objective(s) 
• Safety and tolerability of repeated doses of GBR 830 in adult patients with AD 
• Effect of repeated doses of GBR 830 on biomarkers of disease activity in adult 
patients with AD. 
6.2. 
Secondary Objective(s) 
• Effect of GBR 830 on clinical efficacy parameters in adult patients with AD. 
• PK of repeated doses of GBR 830 in adult patients with AD. 
• Immunogenicity of GBR 830 in adult patients with AD. 
6.3. 
Exploratory Objective(s) 
• Additional exploratory objectives to understand the mechanism of GBR 830 
including effect on cellular infiltrates and immune pathways 

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7. 
STUDY DESIGN 
7.1. 
Study Type/Design 
The study is a phase IIa, double-blind, randomized, placebo-controlled, repeated dose study to 
evaluate safety, biological activity and PK of GBR 830 in adult patients with AD.  The study will 
be conducted in approximately 16 centers in US/Canada.  The study will be conducted in three 
phases: screening phase, treatment phase and follow-up phase. 
During the screening phase, after providing informed consent, all patients will be screened for 
eligibility prior to inclusion in the study and sufficient number of patients will be screened to 
ensure approximately 60 to 80 patients meeting the eligibility criteria will be randomized.  At 
screening, patients will be assessed on EASI, IGA, SCORAD and BSA rating scales for AD.  
Patients will be withdrawn from use of other medication being used to control their AD as 
mentioned in prior and concomitant medication section.  On Day 1, prior to dosing, patients will 
be reassessed on EASI, IGA, SCORAD and BSA rating scales for AD to ensure that they qualify 
for the study. 
A sufficient number of patients will be randomized such that approximately 40 evaluable 
patients complete at least the Day 29 visit.  Approximately -60 to 80 patients are planned to be 
randomized in a ratio of 3:1 to receive GBR 830 (10 mg/kg) or placebo, in a two-arm, parallel 
design study.   
Patients who meet eligibility criteria will undergo Day 1/baseline assessments, randomization, 
and then receive the first IV infusion of GBR 830 or placebo.  Each patient will receive two 
doses of GBR 830 or placebo administered 4 weeks apart on Day 1 and Day 29.  Patients will be 
closely monitored at the study site for 6 hours after the first infusion (Day 1/baseline) and for 3 
hours after the next dose (Day 29).  Patients will return for follow-up visits as mentioned in 
Appendix 1  - schedule of events.  The study site will contact patients by telephone 
approximately 24 hours after each infusion (Days 2 and 30) for concomitant medications and 
procedures, and a general AE query.  
Apart from the dosing visits, patients will be seen in the clinic on Day 4, 8, 15, 22, 29, 32, 36, 43, 
50, 57, 71 and the end of study visit occurs on Day 85 (week 12) for study assessments and PK 
sample collection. 
Skin punch biopsy samples for biomarker analysis will be collected at Day 1/baseline, Day 29 
and Day 71.  Analyses will be performed where samples are available.  A gene/mRNA 
expression profiling will be performed to evaluate the effects of OX40 blockade on both lesional 
and non-lesional skin from patients with AD.  Changes in gene expression in the AD 
transcriptome of lesional skin in comparison to a non-lesional molecular phenotype will be used 
to evaluate treatment-associated effects.  In addition any correlation with improvements in 
disease activity and clinical outcomes will also be evaluated.   
The end of the study will be the date of the last study visit for the last patient in the study. 
An overview of the study design is shown in Figure 1. 

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Figure 1 
Study Design Schematic 
 
 
Figure 2 
Study Flow Chart 
 
* Visits and assessments done in relation to the second infusion will be calculated from the 
actual day/start time of the second infusion.  This applies to V8 to V11, inclusively.  For V12, 
V13, and V14, the time points for assessment will be 672hr, 1008hr, and 1344hr, respectively, 
from the start time of the second infusion.  
7.1.1. 
Screening Phase 
Screening will occur between Day -30 and Day -1.  The purpose of the Screening Visit is to 
obtain informed consent and to establish protocol eligibility.  Informed consent will be obtained 
after the study has been fully explained to each patient and before the conduct of any screening 
procedures or assessments.  Procedures to be followed when obtaining informed consent are 
detailed in Section 15.3. 
The study participants must be adult male and female patients with AD. 
  
 
GBR 830 10mg/kg  
Placebo  
N=60 to 80 
randomized 
3:1 (active to 
placebo) 
 
Dose 1 
Screening 
Day -30-1 
29 
71 
85 
Dose 2* 
1 
 
 
Baseline biopsies 
Repeat biopsies 
 
Repeat biopsies 

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The Screening Disposition eCRF page must be completed to indicate whether the patient is 
eligible to participate in the study and to provide reasons for screen failure, if applicable. 
At screening, patients will be assessed on EASI, IGA, SCORAD, and BSA for AD.  Patients will 
be withdrawn from use of other medication being used to control their AD as mentioned in prior 
and concomitant medication section.  On Day 1, prior to dosing, patients will be reassessed on 
EASI, IGA, SCORAD and BSA for AD to ensure that they qualify for the study. 
7.1.2. 
Treatment Phase 
The treatment phase consists of the 2 visits (Days 1 and Day 29) which correspond to the study 
drug dosing days.  Study drug IV infusions will be given on these days.  Patients will undergo 
baseline biopsies on Day 1 (pre-dose).  All patients will have visit procedures as defined in 
Appendix 1. 
7.1.3. 
Follow-up  
Apart from the dosing visits, patients will be seen in the clinic on Day 4, 8, 15, 22, 29, 32, 36, 43, 
50, 57, 71 and the end of study visit occurs on Day 85 (week 12) for study assessments and PK 
sample collection.  Patients will undergo repeat biopsies on Day 29 (pre-dose) and Day 71. 
7.1.4. 
Extension Phase 
There is no extension phase planned for this study. 
7.2. 
Discussion of Study Design, Including Choice of Control Groups 
The main objective of this phase IIa signal search study is to evaluate the effect of repeated doses 
of GBR 830 on biomarkers of disease activity in adult patients with moderate to severe AD.  The 
objectives are exploratory in nature to further understand the mechanism of GBR 830 with the 
help of biomarker data.  Recently, improvements of the AD molecular signature were observed 
in patients after treatment with dupilumab (Hamilton et al, 2014; Beck et al, 2014), a targeted 
Th2 antagonist, and these changes occurred earlier and were larger than clinical endpoints, 
suggesting that these are valid endpoints for an exploratory study.  Placebo control will provide 
internal validity for the clinical trial and will improve the sensitivity of the clinical trial for drug 
related changes and hence suited for an exploratory study.   

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8. 
STUDY ENDPOINT(S) 
8.1. 
Primary Endpoint(s) 
• All TEAEs occurring in the study, in terms of nature, onset, duration, severity, 
relationship and outcome of AEs and SAEs, in adult patients with moderate-to-severe 
AD. 
• Effect of GBR 830 in adult patients with AD in terms of change from baseline in the 
active AD mRNA expression signature and the pathologic epidermal phenotype 
measures obtained from skin biopsies. 
8.2. 
Secondary Endpoint(s) 
• Proportion of patients who achieve an IGA score of 0 or 1 at each study visit 
• Proportion of patients who achieve an EASI 50 and 75 response at each study visit 
• Percent improvement in clinical scores EASI, SCORAD, IGA, BSA, Pruritus NRS 
and DLQI from baseline to each visit 
• Changes from baseline AD activity as determined by changes in TEWL 
• PK of GBR 830 in adult patients with moderate to severe AD in terms of: Cmax, 
AUC0-tau, AUC0-∞, and AUC0-t, t1/2, volume of distribution, clearance and other 
parameters assessed as relevant after the first and last doses 
• Anti-drug antibodies to GBR 830 to evaluate immunogenicity.  
8.3. 
Exploratory Endpoint(s) 
• Cytokines and chemokines in serum:  Interleukin (IL)-22, IL-13, chemokine ligand 
(CCL)-17 (TARC = thymus and activation-regulated chemokine), Eotaxin (CCL11), 
TSLP, CXCL10 (IP-10), CCL2 (MCP-1), CCL20 (MIP3A),CCL22 (MDC), CCL3 
(MIP-1α), CCL4 (MIP-1β), CCL13 (MCP-4), CXCL11 (IP-9; I-TAC), and CXCL9 
(MIG). 
• Leukocyte sub-population cell counts (Total T, T helper, Cytotoxic T, Tregs, Memory 
T cells). 
• Cellular infiltrates (T-cells, dendritic cells) as assessed by CD3, FcEpsilon RI, 
OX40L, OX40, and MBP. 
• Serum total Immunoglobulin E (IgE), serum soluble OX40 (SOX40), serum soluble 
OX40 ligand (sOX40L),  and circulating eosinophil counts. 

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8.4. 
Appropriateness of Measurements 
All clinical assessments are standard measurements commonly used in studies of AD.  The 
safety assessments in this study are standard evaluations to ensure patient safety.  The 
immunogenicity assessment is standard for a monoclonal antibody therapy. 
9. 
PATIENT SELECTION AND WITHDRAWAL CRITERIA 
Approximately 60 to 80 patients are planned to be randomized in approximately 16 sites in 
regions that include US/Canada, such that approximately 40 evaluable patients complete at least 
the Day 29 visit.  Patients who do not meet all of the inclusion criteria or who meet any of the 
exclusion criteria will not be eligible to receive investigational products. 
Patient eligibility should be reviewed and documented by an appropriately qualified member of 
the Investigator’s study team before patients are included in the study. 
Patients, who fail screening on any single criterion, where there is the prospect of their 
subsequently becoming eligible, may be re-screened on 1 occasion only.   
The eligibility of a patient with respect to laboratory criteria will be assessed according to the 
central laboratory result for the screening sample(s). 
9.1. 
Inclusion Criteria 
Patients eligible for enrolment in the study must meet all of the following criteria: 
1. Male or female patients, age ≥ 18 years at the time of informed consent with physician 
diagnosis of AD for > 1 year; diagnosis of AD as defined by the Hanifin and Rajka 
(Hanifin and Rajka, 1980) criteria for AD. 
2. AD involvement of ≥ 10% body surface area prior to randomization.  
3. EASI score of ≥ 12 prior to randomization; SCORAD of ≥ 20 prior to randomization; 
baseline IGA score of ≥ 3 prior to randomization; and history of inadequate response to a 
stable (> 1 month) regimen of class 3 or higher strength topical corticosteroids (TCS), or 
calcineurin inhibitors or for whom topical treatments are otherwise inadvisable (e.g., 
because of important side effects or safety risks)* 
*NOTE: For the purpose of this protocol, inadequate response represents failure to 
achieve and/or maintain remission or a low disease activity state (e.g., IGA 0=clear to 
2=mild) despite treatment with topical corticosteroids of medium to high potency, or 
topical calcineurin inhibitors as appropriate.  Inadequacy of response will be determined 
based on failure to maintain a low disease activity state despite applications of topical 
medications on a less intensive maintenance schedule (i.e., 2 days per week).  Important 
side effects or safety risks are those that outweigh the potential treatment benefits (e.g., 
hypersensitivity reactions, significant skin atrophy, systemic effects, etc., or imminence 

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thereof), as assessed by the investigator or by patient’s treating physician.  Medical 
history provided by physician and/or patient will be used. 
4. Patient’s body mass index (BMI) should be within the range 18.5–35 kg/m2 (inclusive); 
weight must be > 50 kg. 
5. Patients deemed fit to receive the study medication, as determined by medical history, 
vital signs, physical examinations, ECG, laboratory studies, and other tests performed 
within 30 days prior to drug administration, as judged by the Investigator. 
6. Patients must agree to the following requirements during the study: 
a. Women of child-bearing potential and men with partners of child-bearing potential 
must ensure that two effective means of contraception are used, by them and/or their 
partners, for the period between signing of informed consent and a minimum of 180 
days after the last dose of study drug. 
Acceptable forms of effective contraception include: 
i. Established use of oral, injected, or implanted hormonal methods of 
contraception. 
ii. Tubal ligation 
iii. Placement of an IUD or IUS. 
iv. Barrier methods only when used consistently with spermicidal 
foam/gel/film/cream or suppository.  Acceptable barrier methods include the 
following: 
(1) Male or female condom. 
(2) Occlusive cap (diaphragm or cervical/vault caps). 
v. Male sterilization (with post-vasectomy documentation of the absence of sperm in 
the ejaculate) (For female patients on the study, the vasectomized male partner 
should be the sole partner for that patient).  If a subject cannot provide written 
documentation of male sterilization, a verbal statement from the subject will 
suffice. 
vi. Maintenance of abstinence when this is in line with the preferred and usual 
lifestyle of the patient (i.e., not periodic abstinence, such as during ovulation) 
judged reliable by the Investigator. 
Patients in relation with a same-sex partner do not need to use contraception, if he/she 
is the sole partner for that patient) 
Of the acceptable forms of effective contraception, at least one method needs to be a 
barrier method. 
b. Male patients should agree not to donate sperm until 180 days after administration of 
the last dose of the study medication.  Female patients should not donate eggs for 180 
days following investigational product administration. 

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c. All female patients must be non-pregnant and non-lactating and test negative for 
pregnancy at the time of screening and prior to randomization. 
7. Female patients of non-child-bearing potential (i.e., are postmenopausal or permanently 
sterilized [bilateral oophorectomy, hysterectomy, bilateral salpingectomy]).  Such 
patients will not be required to use contraception.   Postmenopausal is defined as at least 
1 year post cessation of menses (without an alternative medical cause) with follicle 
stimulating hormone (FSH) ≥ 40.0 mIU/mL. 
8. Provide written informed consent. 
9. Willing and able to comply with all aspects of the protocol including willingness to 
undergo 4 on study skin biopsies. 
9.2. 
Exclusion Criteria 
Patients meeting any of the following criteria must not be enrolled in the study: 
1. Patients with a history of drug or other allergy considered clinically significant in the 
opinion of the Investigator, which contraindicates participation or a previous history of 
hypersensitivity to murine proteins. 
2. Patients who have had a live vaccination within 12 weeks before randomization, or intend 
to have a live vaccination during the course of the study, or have participated in a vaccine 
clinical trial within 12 weeks prior to randomization 
3. History of a serious local infection, systemic infection, or gastrointestinal infection within 
12 weeks of baseline; infections requiring systemic antibiotic/ anti-viral/ anti-parasitic/ 
anti-fungals within 4 weeks of baseline; evidence of clinically significant active infection, 
or fever ≥38.0oC (100.4oF) within one week prior to randomization. 
4. Patients who have evidence of active or latent tuberculosis as documented medical 
history, or test positive for QuantiFERON Gold Blood TB Test. 
5. Patients with evidence of skin conditions at screening that would interfere with 
evaluations of the study drug. 
6. Treatment with systemic corticosteroids within 4 weeks before randomization, and 
topical steroids/ tacrolimus and or/pimecrolimus within 1 week before the randomization 
(except emollients, and mild steroids (class 6 or 7). 
7. Treatment with systemic therapy for AD (such as psoralen and ultraviolet A light therapy, 
cyclosporine, methotrexate, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, 
azathioprine), or phototherapy (including ultraviolet B or self-treatment with tanning 
beds or therapeutic sunbathing) within the 4 weeks before randomization or other drugs 
with potential for immunosuppression such as cytotoxic agents or cyclophosphamide 
taken within 4 weeks prior to randomization. 

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10. Any cell-depleting agents including but not limited to rituximab: within 6 months prior to 
the baseline visit, or until lymphocyte and CD 19+ lymphocyte count return to normal, 
whichever is longer.  Other biologics: within 5 half-lives or 8 weeks prior to the baseline 
visit, whichever is longer.  Allergen immunotherapy within 6 months before the baseline 
visit. 
11. Patients who are immunocompromised, have had a recent (within 3 months before 
randomization) or current serious systemic or local infection (including infectious 
mononucleosis-like illness or herpes zoster) suggestive of immunocompromise. 
12. Patients who have current or a history of lymphoproliferative disease or history of 
malignant disease; or signs or symptoms suggestive of possible lymphoproliferative 
disease, including lymphadenopathy or splenomegaly; or active primary or recurrent 
malignant disease. 
13. Patients with history or presence of other inflammatory or auto-immune disease or 
rheumatological or joint diseases other than AD. 
14. History of parasitic infections within 1 year before randomization 
15. History of alcohol or drug abuse or dependence within 2 years of the screening visit. 
16. Patients with a positive result from the drug and alcohol screen. 
17. Patients who test positive for disease markers of HIV, Hepatitis B or Hepatitis C. 
18. Patients with an abnormal ECG (including a QTc >450 msec for men, >460 msec for 
women) considered clinically significant in the opinion of the Investigator at screening 
and/or prior to randomization.  (QTc calculated based on Fridericia’s formula). 
19. Patients with lab values, which are significantly different from normal reference ranges 
(as defined in Appendix 2) and/or judged clinically significant by the Investigator, 
including but not limited to: 
− Patients with eGFR <60 mL/min/1.73m2 as determined by the MDRD method. 
− ALT or AST ≥2.5 times ULN, and/or serum total bilirubin ≥1.5 times ULN, at 
screening. 
− Hb value less than 9 g/dL at screening. 
− Absolute neutrophil count ≤1,500/µL or absolute lymphocyte count ≤800/μL or 
platelet count ≤150,000/µL or any abnormal evaluations judged clinically 
significant by the Investigator at screening and prior to randomization. 
20. Patients with any evidence of organ dysfunction or any clinically significant medical 
history, or findings in physical examinations or investigations or have a clinical condition 
or receiving therapy that, in the opinion of the Investigator, would make the patients 
unsuitable for study. 

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21. Patients with a history of current or previous psychiatric illnesses or previous psychiatric 
events that would either put the patient at undue risk or interfere with study procedures 
according to the investigator. 
22. Treatment with an investigational drug within 8 weeks or within 5 half-lives, if known 
(whichever is longer), before the baseline visit. 
9.3. 
Study Termination, Patient Discontinuation/Withdrawal Criteria 
9.3.1. 
Study Termination Criteria 
If, in the opinion of the Investigator, the clinical observations in the study suggest that it may be 
unwise to continue, the Investigator may terminate his participation in the study, after 
consultation with the Sponsor.  In addition, the Sponsor may terminate part of, or the entire 
study, for safety or administrative reasons.  A written statement fully documenting the reasons 
for study termination will be provided to the Institutional Review Board (IRB)/ Independent 
Ethics Committee (IEC) and the Regulatory authorities.   
9.3.2. 
Patient Discontinuation/Withdrawal Criteria 
A patient may voluntarily discontinue study participation at any time after giving informed 
consent and before the completion of the follow-up visit (Visit 14 - Day 85).  The Investigator 
may also discontinue the patient’s study participation at any time at his/her discretion and for any 
reason.   
The reasons for patient withdrawal will be recorded and may include, but are not limited to: 
• Withdrawal of consent by the patient to continue in the study.  
• Development of a serious or intolerable AE that necessitates discontinuation at the 
discretion of the Investigator (AE section of eCRF must be completed; includes SAE, 
death). 
• At the discretion of the Investigator, when he/she believes continued participation is 
not in the best interest of the patient. 
• At the discretion of the Investigator, when the patient does not adhere to the study 
procedures or restrictions. 
• Protocol deviation that, in the opinion of the Sponsor and Investigator, warrants 
discontinuation from the study. 
• A positive pregnancy test. 
• A patient requires concomitant medications, which may interfere with the PK of the 
study drug.  Note: withdrawal in such cases will be discussed and mutually agreed by 
the Investigator and the Sponsor. 
• Patients requiring rescue medications or interventions. 

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• The patient for any reason requires treatment with another therapeutic agent that has 
been demonstrated to be effective for the treatment of AD.  In this case, 
discontinuation from the study should occur prior to introduction of the new agent. 
• Disease progression/exacerbation, which in the opinion of the Investigator would 
require interruption of treatment or premature termination of follow up.   
• Patients randomized in the study who withdraw their consent for the first post-
baseline skin biopsies. 
The decision to discontinue dosing in a patient due to adverse drug effects will be made on the 
basis of clinical severity and relatedness to study drug.  Except in cases of emergency, it is 
recommended that the Investigator consult with the Sponsor’s medical monitor (MM) before 
removing the patient from the study. 
In case of premature discontinuation, the reason and their cause must be documented.  The 
Investigator (or designee) must document the reason for withdrawal in the End of Study section 
of the eCRF. 
All Follow-up assessments of Visit 14 (Day 85) should be conducted at the Early Withdrawal 
Visit. 
Patients discontinued from the study at any stage will be considered for safety and PK analysis.  
Patients who are permanently discontinued from study drug due to reasons other than an AE and 
before the first post baseline skin biopsies or before receiving two doses of study drug, will not 
be considered evaluable for the Biological Analysis Set (see Section 13.2). 
9.3.2.1. 
Data Collection for Patients Who Permanently Discontinue Study Drug 
1. For patients who permanently discontinue study drug and agree to be followed for safety 
and PK: 
The patient will continue to return for visits as per timing of the visits listed in 
Appendix 1.  For these visits, the safety and PK procedures listed in Section 11.9 should 
be performed.  At the last visit (V14, Day 85) the entire End of Study Assessment should 
be performed as described in Section 11.8. 
23. For patients who permanently discontinue study drug and are not willing to continue in 
the study: 
The end of study assessments (V14, D85) should be performed at this early withdrawal 
visit.   
9.3.3. 
Sponsor Discontinuation Criteria 
Premature termination of this study may occur because of a regulatory authority decision, change 
in opinion of the Institutional Review Board (IRB)/Independent Ethics Committee (IEC), drug 
safety problems, or at the discretion of Glenmark.  In addition, Glenmark retains the right to 
discontinue development of GBR 830 at any time. 

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If a study is prematurely terminated or discontinued, Glenmark will promptly notify the 
Investigator.  After notification, the Investigator must contact all participating patients and the 
hospital pharmacy (if applicable) within a time period set by Glenmark.  As directed by 
Glenmark, all study materials must be collected and all CRFs completed to the greatest extent 
possible. 
9.4. 
Prior and Concomitant Medication(s) 
Prohibited Prior Medication: 
• Treatment with systemic corticosteroids within 4 weeks before randomization, and 
topical steroids/ tacrolimus and/or pimecrolimus within 1 week prior to 
randomization except emollients, and mild steroids (class 6 or 7), applied other than 
on target area that will be the site for the skin biopsies.  Nasal and inhaled 
corticosteroids use is allowed during study. 
• Treatment with systemic therapy for AD (such as psoralen and ultraviolet A light 
therapy, cyclosporine, methotrexate, mycophenolate mofetil, thioguanine, 
hydroxyurea, sirolimus, azathioprine), or phototherapy (including ultraviolet B or 
self-treatment with tanning beds or therapeutic sunbathing) within 4 weeks before 
randomization. 
• Other drugs with potential for immunosuppression such as cytotoxic agents or 
cyclophosphamide taken within 4 weeks prior to randomization.   
• Any cell-depleting agents including but not limited to rituximab: within 6 months 
prior to the baseline visit, or until lymphocyte and CD 19+ lymphocyte count return 
to normal, whichever is longer.  Other biologics: within 5 half-lives or 8 weeks prior 
to the baseline visit, whichever is longer.  Allergen immunotherapy within 6 months 
before the baseline visit.   
• Complementary or alternate therapies for the treatment of AD/inflammatory 
conditions.  However patients can be included subsequent to an adequate wash-out 
period (14 days or five half-lives of the complementary or alternate therapy prior to 
randomization, whichever is longer). 
Prohibited Concomitant Medication: 
• All restrictions on the medications listed above in the “prior medication” are 
applicable for the entire duration of the study.  
Other concomitant medications that the patient receives on a regular basis may continue if in the 
opinion of the investigator it does not put the patient at undue risk or nor interfere with the study 
evaluations.  Patients should be stable on allowed concomitant medication for at least 3 months 
prior to randomization.  Oral contraception must have been taken for a sufficient duration for the 
medication to be effective according to the product labelling.   

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• Antihistamines are not allowed on a PRN basis, but they can be taken during the 
study if the patient has been on a stable dose for 3 months and continues on that 
stable dose for the entire study duration.   
• “Stable” dose would be a daily dose (unless recommended dosing differs from the 
usual daily regimen) taken 3 months before and continuing throughout the study, to 
ensure continuity of any effect.  
• If the patient has not been on a stable dose for the past 3 months, the subject should 
either: 
− Have a 4 weeks washout before being randomized into the study 
− Be put on stable dose for 3 months. 
• There are miscellaneous medications taken PRN that could be allowed, if they are not 
expected to have an effect on study parameters, e.g., acetaminophen PRN for 
headache.  Drug with immunosuppressant effects or any prohibited medications are 
not allowed.   
• During the study, if a subject develops allergy symptoms due to allergic 
rhinitis/allergic conjunctivitis, this subject may use topical nasal sprays/eye drops, but 
no PRN oral antihistamines will be allowed. 
All concomitant medications taken by the patient shall be recorded in the patient diary and Prior 
& Concomitant Medication Forms of eCRF. 
9.4.1. 
Rescue Medication(s) 
In case a patient has a severe flare of disease or severe infection that are deemed by the 
investigator as necessitating withdrawal from the study and instituting rescue medications, the 
study medication will be permanently discontinued and the subject will be placed on alternative 
treatment as soon as possible according to the medical need.  These patients will be followed for 
the whole period of study follow-up (week 12) in order to obtain protocol-specified safety 
information.  Efficacy evaluations will not be performed during this safety follow-up period.  If 
the patient dropped out after Day 29 treatment and biopsies, he will be considered as an 
evaluable patient for the study.   
9.5. 
Lifestyle and/or Dietary Restrictions 
Women of child-bearing potential and men with partners of child-bearing capacity must ensure 
that two highly effective means of contraception are used, by them and their partners, for the 
period between signing of informed consent and a minimum of 180 days after dosing.  

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9.5.1. 
Contraception 
Women of child-bearing potential and men with partners of child-bearing potential must ensure 
that two highly effective means of contraception are used, by them and/or their partners, for the 
period between signing of informed consent and a minimum of 180 days after dosing. 
Acceptable forms of effective contraception include: 
• Established use of oral, injected, or implanted hormonal methods of contraception.   
• Tubal ligation. 
• Placement of an IUD or IUS. 
• Barrier methods only when used consistently with spermicidal foam/gel/film/cream 
or suppository.  Acceptable barrier methods include the following: 
− male or female condom  
− occlusive cap (diaphragm or cervical/vault caps)  
• Male sterilization (with post-vasectomy documentation of the absence of sperm in the 
ejaculate) (For female patients on the study, the vasectomized male partner should be 
the sole partner for that patient). 
• Maintenance of abstinence when this is in line with the preferred and usual lifestyle 
of the patient (i.e., not periodic abstinence, such as during ovulation) in a patient 
judged reliable by the Investigator. 
Of the acceptable forms of effective contraception, at least one method needs to be a barrier 
method. 
Notes: 
• Female patients not of childbearing potential (i.e. are postmenopausal or permanently 
sterilized [bilateral oophorectomy, hysterectomy, bilateral salpingectomy]).  Such 
patients will not be required to use contraception. 
• Postmenopausal is defined as at least one year post cessation of menses (without an 
alternative medical cause) with concentrations of FSH ≥ 40 mIU/mL. 
• Male patients should not donate sperm for 180 days following investigational product 
administration.  Female patients should not donate eggs for 180 days following 
investigational product administration. 

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10. 
TREATMENT OF PATIENTS 
10.1. 
Treatments Administered 
• GBR 830 is provided as liquid filled vial formulation available in 10 mL volumes 
containing GBR 830 at concentrations of 10 mg/mL.  GBR 830 solution for infusion 
will be prepared in normal saline.   
• Placebo is provided as liquid filled vial formulation available in 10 mL volumes 
containing the formulation buffer.  Placebo solution for infusion will be prepared in 
normal saline. 
• The GBR 830 dose will be 10 mg/kg.   
Administration: investigational product will be administered by continuous slow IV infusion 
over 60 mins using a commercially available, validated, infusion pump. 
10.1.1. 
Administration 
Appropriate aseptic technique should be used while preparing and administering infusions.  
GBR 830 is provided as liquid filled vial formulation available in 10 mL volumes containing 
GBR 830 at concentrations of 10 mg/mL. 
The investigational product will be diluted with normal saline and administered after normalizing 
for body weight by continuous slow IV infusion over 60 minutes (+/- 5 mins) using 
commercially available volumetric or syringe infusion pumps.  The infusion is to be performed 
with the patient in a supine position and/or semi-supine position, with proper documentation 
noted in the medical records at the site.   
The infusion volume must be calculated using the patient’s current body weight.  In the event of 
an infusion reaction, for the purposes of patient safety, the rate of infusion may be decreased and 
the duration extended at the Investigator’s discretion.  The pharmacist or designee under the 
direction of the investigator will dispense study drug for each patient according to the protocol 
and the randomization number assigned through Interactive voice response system / Interactive 
web response system (IVRS/IWRS).  The diluted investigational product should be used within 
24 hours and must be stored at 2 to 8°C prior to use.  Details of the volume of investigational 
product required, the concentration to be made, the volume of final infusion to be administered, 
the infusion sets, and material to be used will be described in a pharmacy manual.   
10.1.2. 
Treatment Compliance 
Compliance will be measured by witnessed investigational product administration at the site.  
Apart from this accountability of vials at the pharmacy, and bio-analytical data will be used to 
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Records of treatment compliance for each patient will be kept during the study.  Clinical research 
associates (CRAs) will review treatment compliance during site visits and at the completion of the 
study. 
10.1.3. 
Treatment of Investigational Product Overdose 
No data are available with regard to overdose of investigational product in humans.  There is no 
specific antidote to be used in the event of overdose with investigational product.  Investigators 
should use their clinical judgment in treating cases of overdose as dictated by the patient's 
clinical status. 
10.2. 
Identity of Investigational Product(s) 
10.2.1. 
Chemical Name and Structural Formula of GBR 830 
Test drug code: 
GBR 830 
Generic name: 
GBR 830 
Chemical name: 
GBR 830 
Structural formula: 
NA 
10.2.2. 
Placebo/Control/Comparator 
Placebo will be formulation buffer, diluted in normal saline and administered as IV infusion over 
60 mins. 
10.2.3. 
Packaging and Labelling of Investigational Product(s) 
GBR 830 drug product (DP) is formulated as a sterile, clear to slightly opalescent, isotonic, 
colorless to slightly yellowish, aqueous solution containing no preservatives and buffered to a pH 
of 6.25 for IV administration after dilution in saline.  GBR 830 will be supplied in 10-mL single 
use vials containing 100.0 mg of GBR 830 (nominal 10 mg/mL).  In addition, each unit dose vial 
contains 15mM Histidine, 150 mM NaCl, pH 6.25, and 0.01% Tween 80.  The GBR 830 solution 
for IV infusion will be prepared in normal saline (commercially available normal saline [0.9% 
sodium chloride].  The placebo for infusion is formulation buffer for IV administration after 
dilution in saline and will be supplied in 10-mL single use vials.  Each unit dose vial contains 
15mM Histidine, 150 mM NaCl, pH 6.25, and 0.01% Tween 80.  The placebo solution for IV 
infusion will be prepared in normal saline (commercially available normal saline [0.9% sodium 
chloride]).   
The investigational product vials must be stored refrigerated (2° to 8°C) and protected from light 
and moisture in a restricted access room at the clinical site.  The vials must be allowed to warm 
to room temperature prior to dispensing.   

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Glenmark Pharmaceuticals Ltd, or their representative, will provide dosing kits for supply to the 
sites.  The patient-specific dosing kits will be packed and labeled by Glenmark Pharmaceuticals 
Ltd or their representative in accordance with Good Manufacturing Practice.  Sufficient supplies 
of dosing kits will be provided to the study sites.  After study completion, all unused GBR 830 
and placebo vials will be destroyed at the clinical site as per the CRO’s SOP or returned to the 
Sponsor, as per written communication from the Sponsor. 
The DPs will be labeled in accordance with text that is in full regulatory compliance with each 
participating country and as necessary translated into the required language(s) for each of those 
countries. 
10.3. 
Allocation to Treatment Groups 
At either a separate consent visit or screening visit, potential study patients will be assigned a 
screening number.  Following confirmation of eligibility, patients will be assigned a 
randomization number through IVRS/IWRS.  The randomization scheme and identification for 
each patient will be included in the final clinical study report (CSR) for this study.  The patient 
allocation and list of dose/patient numbers are mentioned in Section 10.1.1. 
The randomization list will be generated using SAS Version 9.1.3 or higher.  All eligible patients 
entering the study will be randomized to the two treatment arms.  If a patient discontinues from 
the study, the patient number will not be re-used and the patient will not be allowed to re-enter 
the study.   
Patients will be randomly assigned to receive either GBR 830 or placebo in a 3:1 ratio.  A 
randomization number that uniquely identifies each patient and the patient’s treatment will be 
assigned on Day 1.  Randomization numbers will be allocated from the schedule in strict 
chronological order.  
A sufficient number of patients (approximately 60 to 80) will be randomized such that 
approximately 40 evaluable patients complete at least the Day 29 visit.   
• For patients randomized prior to protocol version 3 (amendment 2) who do not 
complete at least the Day 29 visit:   
A replacement patient will be given the patient number corresponding to the person 
he/she is replacing plus 100.  For example, at site 01, if randomized patient 011001 is 
to be replaced, the subject number for the replacement randomized patient would be 
011101.  Randomized replacement patient 011101 will receive the same treatment 
assignment (via IWRS) as the original randomized patient 011001 had received.   
• For patients randomized after protocol version 3 (amendment 2 who do not complete 
at least the Day 29 visit: 
Replacement of patients (to receive the same treatment assignment as the original 
subject he/she is replacing) will no longer be performed.  
Randomization will be done using IVRS/IWRS software. 

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10.4. 
Blinding and Unblinding Procedures 
The study will be conducted in a double-blind manner.  The sponsor will be blinded to the 
identity of the investigational product and all study data.  In the event of a medical emergency 
when management of a patient’s condition requires knowledge of the trial medication, 
IVRS/IWRS will be used to determine the nature of the trial medication dispensed.  If possible, such 
emergencies should be discussed with the study monitor and the Sponsor prior to disclosure of 
the treatment allocation.  Reasons for breaking a code must be clearly explained and justified in 
the eCRF.  The date on which the code was broken together with the identity of the person 
responsible must also be documented. 
The following controls will be employed to maintain the double-blind status of the study: 
• The placebo will be identical in appearance to the GBR 830 infusion 
• The Investigator and other members of staff involved with the study will remain 
blinded to the treatment randomization code during the assembly procedure 
• Any interim data will be provided in a blinded manner 
With the exception of the statistician (who is not a study team member) preparing the 
randomization and personnel involved in packaging, all clinical and non-clinical staff will 
remain blinded to the treatment allocation until after the database is locked unless there is a 
medical event that requires a code break. 
10.5. 
Investigational Product(s) Preparation, Receipt, Storage, Dispensing 
and Accountability 
Investigational product must be stored between 2°C and 8°C.  Do not freeze or shake.  The 
investigator (or designee) is responsible for study drug accountability at the site and its 
documentation.  The investigator must also ensure that the dispensing and recording of study 
drug is performed only by authorized personnel.  The study drug records must be readily 
available for inspection by the study monitor and/or auditor/regulatory agency personnel.  No 
medication (new or used) can be returned to the Sponsor or disposed of at the investigational site 
until the  clinical monitor has verified/reconciled the accuracy of the study drug records at the 
site and indicated whether the study drug should be destroyed at the site or returned to the 
Sponsor.  The study monitor must indicate the name and address of the individual to whom the 
returned materials should be shipped. 
Clinical staff will dispense the dosing kits at the visits specified in the study protocol.  The 
preparation of the infusion solutions (GBR 830 and placebo) will be performed by a licensed 
pharmacist or trained designee under the direction of the investigator.  The Investigational 
product will be diluted with a standard 0.9% sodium chloride solution to yield a uniform solution 
for IV infusion.  Foaming or excessive shearing of the protein solution must be avoided.  The 
preparation must be carefully inspected; it should result in a homogeneous-looking clear solution 
free of visible particles.  Direct sunlight should be avoided.  The details of preparation and 

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storage of the infusions are presented in a pharmacy manual.  At the time of dispensing, a 
mandatory verification by a second staff member has to be performed. 
11. 
TIMING OF STUDY PROCEDURES AND ASSESSMENTS 
Study procedures and assessments are summarized across all study visits within the Schedule of 
Events (Appendix 1 ).  The visit windows are mentioned below. 
Window for collection of samples for GBR-830 PK analysis: 
• V2 and V7:  
o Pre-dose: within 15 minutes before administration of each dose 
o Post-dose: 
 immediately at the end of each infusion± 10 mins;  
 1.5 hrs ± 10 mins estimated from the start time of infusion 
 2 hrs ± 10 mins estimated from the start time of infusion 
 4 hrs ± 10 mins estimated from the start time of infusion 
• V3 and V8: 72 hrs ± 24 hrs estimated from the start time of infusion  
• V4 and V9: 168 hrs ± 24 hrs estimated from the start time of infusion 
• V5 and V10: 336 hrs ± 24 hrs estimated from the start time of infusion 
• V6 and V11: 504 hrs ± 48 hrs estimated from the start time of infusion 
• V12, V13, V14: 1344 hrs (Day 57) ± 48 hrs, 1680 hours (Day 71) ± 48 hrs, and 2016 
hours (Day 85) ± 48 hrs estimated from the start time of first infusion.  Visits and 
assessments done in relation to the second infusion will be calculated from the actual 
day/start time of the second infusion.  This applies to V8 to V11, inclusively.  For V12, 
V13, and V14, the time points for assessment will be 672hr, 1008hr, and 1344hr, 
respectively, from the start time of the second infusion.   
Window for vital signs:  
• V2 and V7:  
o Pre-dose: within 30 minutes before administration of each dose 
o Post-dose: 
 Every half hour during infusion ± 10 mins;  
 0.5 hrs ± 10 mins estimated from the end time of infusion 
 1 hr ± 10 mins estimated from the end time of infusion 
 2 hrs ± 10 mins estimated from the end time of infusion 
 6 hrs ± 10 mins (In V2 only) estimated from the end time of infusion 
 3 hrs ± 10 mins (In V7 only) estimated from the end time of infusion 
• V3 and V8: 72 hrs± 24 hrs estimated from the start time of infusion 
• V4 and V9: 168 hrs ± 24 hrs estimated from the start time of infusion 
• V5 and V10: 336 hrs ± 24 hrs estimated from the start time of infusion 
• V6 and V11: 504 hrs ± 48 hrs estimated from the start time of infusion 

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• V12, V13, V14: 1344 hours (Day 57) ± 48 hrs, 1680 hours (Day 71) ± 48 hrs, and 2016 
hours (Day 85) ± 48 hrs estimated from the start time of infusion.  Visits and assessments 
done in relation to the second infusion will be calculated from the actual day/start time of 
the second infusion.  This applies to V8 to V11, inclusively.  For V12, V13, and V14, the 
time points for assessment will be 672hr, 1008hr, and 1344hr, respectively, from the start 
time of the second infusion.  
Window for ECG recording: 
• V2:  
o Pre-dose: before administration of each dose 
o Post-dose: 2hrs ± 30 mins and 6hrs ± 30 mins estimated from the end time of 
infusion 
• V3 and V8: 72 hrs± 24 hrs estimated from the start time of infusion 
• V4 and V9: 168 hrs ± 24 hrs estimated from the start time of infusion 
• V7: 
o Pre-dose: before administration of each dose 
o Post-dose: 2hrs ± 15 mins and 3hrs ± 15 mins estimated from the end time of 
infusion 
• V12, V13, V14: 1344 hours (Day 57) ± 48 hrs, 1680 hours (Day 71) ± 48 hrs, and 2016 
hours (Day 85) ± 48 hrs estimated from the start time of first infusion.  Visits and 
assessments done in relation to the second infusion will be calculated from the actual 
day/start time of the second infusion.  This applies to V8 to V11, inclusively.  For V12, 
V13, and V14, the time points for assessment will be 672hr, 1008hr, and 1344hr, 
respectively, from the start time of the second infusion.  
For all other safety and pharmacodynamics/biomarker/immunogenicity assessments:  
• V2: before administration of each dose 
• V3 and V8: 72 hrs± 24 hrs estimated from the start time of infusion 
• V4 and V9: 168 hrs ± 24 hrs estimated from the start time of infusion 
• V5 and V10: 336 hrs ± 24 hrs estimated from the start time of infusion 
• V6 and V11: 504 hrs ± 48 hrs estimated from the start time of infusion 
• V7: before administration of each dose\ 
• V12, V13, V14: 1344 hours (Day 57) ± 48 hrs, 1680 hours (Day 71) ± 48 hrs, and 2016 
hours (Day 85) ± 48 hrs estimated from the start time of first infusion.  Visits and 
assessments done in relation to the second infusion will be calculated from the actual 
day/start time of the second infusion.  This applies to V8 to V11, inclusively.  For V12, 
V13, and V14, the time points for assessment will be 672hr, 1008hr, and 1344hr, 
respectively, from the start time of the second infusion.   
In the event that assessments are planned for the same scheme time, the order of the assessments 
should be arranged in such a way that PK blood sampling will be performed first, followed by 
ECG and vital signs, with blood sampling exactly on time.  Samples collected outside the 

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window period will be reported as protocol deviations and the actual time point of sampling will 
be recorded. 
11.1. 
Screening: Visit 1 
Patients will go to the site for a screening visit up to 30 days prior to study drug administration 
Day 1.  Informed consent must be obtained at this visit prior to any study procedures are 
performed.  Further details regarding informed consent are provided in Section 15.3. 
A screening log will be kept to record patients who sign the informed consent form (ICF) and 
who are screened.  For those patients who are screen failures, a reason for the failure will be 
documented.  Prior to performing any procedures or assessments, the nature of the study and the 
potential risks associated with the study must be explained to the patient and written informed 
consent must be obtained.  Once informed consent has been obtained, the following procedures 
and evaluations will be performed and recorded.  
• A diary, used for the itching scale and other observations required for screening, will 
be given to each patient when the patient begins the screening period.  Patient will be 
trained on the use of diary.  Patient will be instructed to enter the data every morning 
at a designated time and how to record them.  Patient must enter data into the diary 
every day from start of screening period to end of study visit.  Demographic 
information (Date of birth and/or age, race and ethnicity, gender) 
• Height and body weight (measured while wearing indoor clothing and no shoes) 
• BMI, calculated as weight (kg)/height (m)2 
• Smoking status / intake of tobacco in any other form (including current and historical 
use of tobacco) 
• Alcohol and drug abuse status/ intake in any form 
• Medical and surgical history 
• Prior and concomitant medications, and AEs 
• Detailed physical examination 
• Vital signs (pulse, BP-blood pressure, temperature) 
• Determine inclusion/exclusion criteria 
• 12-lead ECG 
• Clinical laboratory tests (collected under fasting conditions; blood sample for 
hematology, biochemistry tests and urine sample for urinalysis). 
• Viral serology (hepatitis B surface antigen [HBsAg], anti- hepatitis B core antigen 
[Anti-HBc], hepatitis C antibody, human immunodeficiency virus [HIV-1and HIV-
2]) 

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• Evidence of active or latent tuberculosis to be documented by medical history or 
QuantiFERON Gold Blood TB Test.  A chest X-ray is not mandatory.  
QuantiFERON Gold Blood TB Test will be performed in all patients  
• Serum Pregnancy test for females (Beta-HCG), serum FSH test for all female patients 
• EASI, SCORAD, IGA, BSA measurements 
One re-test will be allowed at screening for investigations other than viral serology at the 
discretion of the investigator in order to confirm findings for clinical conditions that are 
considered to be acute, reversible, and non-serious. 
11.2. 
Dosing visits (Visits 2 and 7) 
The visit 2 will be the baseline visit.  Patients will arrive at the study site on the day of dosing 
(Day 1, Visit 2 and Day 29±1, Visit 7) and will be closely monitored at the study site for 6 hours  
after the first injection (Day 1/baseline, Visit 2) and for 3 hours after the next dose (Day 29, Visit 
7).  The following procedures will be conducted and recorded: 
• Eligibility criteria and randomization procedures including pre-study restrictions 
(Visit 2 only) 
• Pre-dose drug and alcohol screen 
• Body weight and BMI 
• Pre-dose brief physical examination of major body systems 
• Whole body photography to be taken at Visit 2 (Day 1) only  
• Pre- and post-dose vital signs: includes supine or semi-supine measurements BP and 
pulse; and body temperature.  Vitals have to be monitored every half hour during 
infusion 
• Pre- and post-dose 12-lead ECG 
• Pre-dose blood samples for routine hematology, biochemistry and urine sample taken 
for routine urine analysis 
• Pre-dose blood samples for serum pregnancy test for females (Beta-HCG) - (Visit 2 
only) 
• Pre-dose urine pregnancy for females only 
• Administration of a single 1-hour IV infusion of IP administered under the 
supervision of trained study personnel 
• Pre-dose EASI, SCORAD, DLQI, IGA, NRS, BSA measurements 
• Blood sample for pre- and post-dose GBR-830 PK analysis 
• Pre-dose skin biopsies 

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• Leukocyte sub-population cell counts (Total T, T helper, Cytotoxic T, Tregs, Memory 
T cells), TEWL, total IgE, eosinophil count 
• Pre-dose blood samples for immunogenicity, cytokine and exploratory analysis 
• Concomitant medications and AEs.  The site will contact the subject 24 hours after 
each infusion by phone  
11.3. 
Follow-up Visits 3 and 8 (Days 4±1 and 32±1)  
• Vital signs (pulse, BP, temperature) 
• 12-lead ECG 
• Clinical laboratory tests (blood sample for hematology, biochemistry and urine 
sample for urinalysis) 
• EASI, SCORAD, DLQI, IGA, NRS, BSA measurements 
• Concomitant medications and AEs 
• Blood sample for GBR-830 PK analysis 
11.4. 
Follow-up Visits 4 and 9 (Days 8±1 and 36±1)  
• Vital signs (pulse, BP, temperature) 
• 12-lead ECG 
• Clinical laboratory tests (blood sample for hematology, biochemistry; and urine 
sample for urinalysis) 
• EASI, SCORAD, DLQI, IGA, NRS, BSA measurements 
• Concomitant medications and AEs 
• Blood sample for GBR-830 PK analysis 
• Leukocyte sub-population cell counts (Total T, T helper, Cytotoxic T, Tregs, Memory 
T cells), TEWL, total IgE, eosinophil count  
• Whole body photograph to be taken at Visit 4 only 
11.5. 
Follow-up Visits 5 and 10 (Days 15±1 and 43±1)  
• Brief physical examination of major body systems 
• Vital signs (pulse, BP, temperature) 
• EASI, SCORAD, DLQI, IGA, NRS, BSA measurements 
• Concomitant medications and AEs 

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• Blood sample for GBR-830 PK analysis 
• Blood samples for immunogenicity analysis in visit 5 (Day 15) 
• Leukocyte sub-population cell counts (Total T, T helper, Cytotoxic T, Tregs, Memory 
T cells), TEWL, total IgE, eosinophil count  
• Whole body photograph to be taken at Visit 10 only 
11.6. 
Follow-up Visits 6 and 11 (Days 22±2 and 50±2)  
• Vital signs (pulse, BP, temperature) 
• EASI, SCORAD, DLQI, IGA, NRS, BSA measurements 
• Concomitant medications and AEs 
• Blood sample for GBR-830 PK analysis 
11.7. 
Follow-up Visits 12 and 13 (Days 57±2 and 71±2)  
• Vital signs (pulse, BP, temperature) 
• 12-lead ECG 
• Clinical laboratory tests (blood sample for hematology, biochemistry and urine 
sample for urinalysis) 
• EASI, SCORAD, DLQI, IGA, NRS, BSA measurements 
• Concomitant medications and AEs 
• Blood sample for GBR-830 PK analysis 
• Blood samples for immunogenicity analysis in visit 12 (Day 57) 
• Blood samples for cytokine analysis and exploratory analysis on visit 13 (Day 71) 
• Skin biopsies on visit 13 (Day 71) 
• Leukocyte sub-population cell counts (Total T, T helper, Cytotoxic T, Tregs, Memory 
T cells), TEWL, total IgE, eosinophil count 
11.8. 
Follow-up Visits (end of study) assessments on Day 85 (±2) include 
the following: 
• Body weight and BMI 
• Brief physical examination of major body systems 
• Vital signs (pulse, BP, temperature) 
• 12-lead ECG 

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• Clinical laboratory tests (blood sample for hematology, biochemistry and urine 
sample for urinalysis) 
• Blood sample for serum pregnancy tests for all women 
• EASI, SCORAD, DLQI, IGA, NRS, BSA measurements 
• Concomitant medications and AEs 
• Blood sample for GBR-830 PK analysis 
• Blood samples for immunogenicity analysis 
• Leukocyte sub-population cell counts (Total T, T helper, Cytotoxic T, Tregs, Memory 
T cells), TEWL, total IgE, eosinophil count 
• Whole body photograph 
11.9. 
Early Withdrawal Visit 
The Early Withdrawal Visit will be performed as applicable (see Section 9.3.2 for additional 
information).  The end of study assessments will be performed for all patients receiving study 
drugs who withdraw prematurely from the study.  Any patient who is withdrawn must be 
followed-up as outlined in Section 9.3 and in Appendix 1, but at least for approximately 
5 half-lives (56 days) after the last infusion. 
In addition, for patients who will be followed for the whole period of study follow-up (week 12) 
in order to obtain protocol-specified safety information, the following safety and PK parameters 
will be evaluated according to Appendix 1.  
• Brief physical examination of major body systems 
• Vital signs (pulse, BP, temperature) 
• 12-lead ECG 
• Clinical laboratory tests (blood sample for hematology, biochemistry, serum 
pregnancy tests for all women, and urine sample for urinalysis) 
• Concomitant medications and AEs 
• Blood sample for GBR-830 PK analysis 
• Blood samples for immunogenicity analysis 
11.10. 
Telephone Monitoring 
For patients who do not make scheduled study visits or are lost to follow-up a telephone follow 
up has to be done to evaluate the reason for non-compliance.  The study site will contact patients 
by telephone approximately 24 hours after each infusion of study drug for concomitant 

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medications and procedures and general AE query.  Written documentation must be maintained 
for all such communications with the patient. 
12. 
STUDY PROCEDURES AND ASSESSMENTS 
12.1. 
Demographic and Other Pretreatment Assessments 
12.1.1. 
Demography 
Patient demography information will be collected at the Screening visit.  Demographic 
information includes date of birth (or age), gender, race/ethnicity, height and weight. 
12.1.2. 
Medical History and Physical Examinations at Screening 
Medical and surgical history and current medical conditions will be recorded at the Screening 
Visit.  Smoking, alcohol and drug abuse history will also be recorded.  All relevant medical and 
surgical history must be noted in the Medical and Surgical History eCRF form.   
Screening Physical examinations will be comprehensive and documentation of the physical 
examination will be included in the source documentation at the site.  Significant findings at the 
Screening Visit will be recorded on the Medical and Surgical History eCRF form.   
12.1.3. 
QuantiFERON Gold Blood TB Test 
A whole blood sample will be collected from each patient at the screening visit for the 
QuantiFERON Gold Blood TB Test.  Detailed instructions for blood sample collection, 
preparation, and shipping are provided in the central laboratory manual. 
In addition, eligibility criteria will be assessed at baseline prior to randomization. 
12.2. 
Efficacy Assessments 
12.2.1. 
EASI  
The EASI is a validated measure used in clinical practice and clinical trials to assess the severity 
and extent of AD.  Four AD disease characteristics will be assessed for severity by the 
investigator or designee on a scale of “0” (absent) through “3” (severe).  In addition, the area of 
AD involvement will be assessed as a percentage by body area of head, trunk, arms, and legs and 
converted to a score of 0 to 6 (Hanifin et al, 2001). 
12.2.2. 
SCORAD 
The SCORAD is a validated tool used in clinical research and clinical practice that was 
developed to standardize the evaluation of the extent and severity of AD (Dermatology 1993 - 
SCORAD Index, 1993).  The extent of AD is assessed as a percentage of each defined body area 
and reported as the sum of all areas, with a maximum score of 100% (assigned as “A” in the 

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overall SCORAD calculation).  The severity of 6 specific symptoms of AD is assessed using the 
following scale: none (0), mild (1), moderate (2), or severe (3) (for a maximum of 18 total 
points, assigned as “B” in the overall SCORAD calculation).  Subjective assessment of itch and 
sleeplessness is recorded for each symptom by the patient or relative on a visual analogue scale 
(VAS), where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or 
sleeplessness), with a maximum possible score of 20.  This parameter is assigned as “C” in the 
overall SCORAD calculation.  The SCORAD is calculated as: A/5 + 7B/2 + C (Kunz et al, 
1997). 
12.2.3. 
IGA 
The IGA is an assessment scale used in clinical studies to determine severity of AD and clinical 
response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe/very severe).  
The proportion of patients who achieve an IGA 0 or 1 score is another key secondary endpoint, 
which will be included in the primary analysis. 
12.2.4. 
NRS  
Pruritus Numerical rating scale (NRS): Patients will record once daily and respond to the 
following question, “On a scale of 0 – 10, with 0 being no itch and 10 being the worst itch 
imaginable, how would you rate your worst degree of itch during the previous 24 hours?” Patient 
compliance on the pruritus NRS will be followed at each clinic visit. 
12.2.5. 
DLQI  
Dermatology Life Quality Index (DLQI): The DLQI is a simple, patient-administered, 
10-question, validated, quality-of-life questionnaire that covers 6 domains including symptoms 
and feelings, daily activities, leisure, work and school, personal relationships, and treatment.  
Response categories include “a little,” “a lot,” and “very much” with corresponding scores of 1, 
2, and 3 respectively and “not at all”, “not relevant” responses scored as “0.” Totals range from 0 
to 30 (less to more impairment) and a 5–point change from baseline is considered clinically 
relevant ((Basra et al, 2008; Finlay and Khan, 1994). 
12.3. 
Pharmacokinetic, Pharmacodynamic, Biomarker and 
Pharmacogenomic Assessments 
12.3.1. 
Pharmacokinetic Assessments 
Blood samples will be collected as per routine phlebotomy procedures and at time points 
specified in the Schedule of Events (Appendix 1).  Briefly, blood samples (1 x 3.5 mL each) will 
be collected during the course of the study through indwelling cannula placed in forearm veins or 
alternatively, by a fresh clean venipuncture using a disposable sterilized syringe and a needle.  
The cannulae will be maintained patent as per local practice.  Do not use heparin.  

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The minute of collection of each blood sample will be recorded.  In any case actual time points 
will be used during PK calculations.   
The details of sample collection, processing and storage will be outlined in a separate lab 
manual.  The samples will be shipped to the specified bioanalytical lab.  Serum concentrations of 
GBR 830 will be quantified using a validated enzyme-linked immunosorbent assay (ELISA) 
method. 
12.3.2. 
Immunogenicity Assessments 
Blood samples will be collected at appropriate time points defined in Appendix 1, to evaluate 
anti-drug antibodies to GBR 830, as per procedures similar to collection of PK samples.  
Antibodies to GBR 830 will be detected and confirmed using a validated ELISA method.  The 
details of sample collection, processing and storage will be outlined in a separate lab manual.  
The samples will be shipped to the specified bioanalytical lab 
12.3.3. 
Biomarker Assessments 
12.3.3.1. Flow cytometry/Leukocyte sub-population cell counts 
Blood samples will be collected at appropriate time points defined in Appendix 1.  The details of 
sample collection, processing and storage will be outlined in a separate lab manual. 
12.3.3.2. Cytokines and Chemokines 
Blood samples will be collected at appropriate time points defined in Appendix 1.  The details of 
sample collection, processing and storage will be outlined in a separate lab manual. 
12.3.3.3. Total IgE 
Patients with AD often have elevated IgE.  Total IgE levels have been found to modestly 
correlate with AD severity and may be involved in the pathogenesis of the disease.  Changes in 
total IgE reflects not only on AD, but atopy in general.  Baseline IgE levels will be assessed for 
potential predictive value for treatment response.  Post-treatment samples will be evaluated for 
effects of GBR 830 on total IgE.  Detailed instructions for blood sample collection will be 
outlined in a separate lab manual.  Blood samples will be collected at appropriate time points 
defined in Appendix 1. 
12.3.3.4. Transepidermal Water Loss 
Transepidermal water loss is a skin barrier function test that measures perspiration or water loss 
through the skin.  This procedure involves the non-invasive application of a probe on the surface 
of the skin on the arm or leg.  Affected and non-affected areas of skin will be tested.  This 
procedure will only be performed at specified study centers.  The detailed procedure for TEWL 
will be provided in the Study Reference Manual. 

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12.3.3.5. Immunohistochemistry (IHC) 
Skin biopsy samples will be collected at appropriate time points defined in Appendix 1.  Two 
punch biopsies (1 from LS and 1 from NLS) will be collected at baseline visit and one punch 
biopsy (from LS) at the subsequent time point.  For LS, biopsy should be taken from a target 
lesion initially and always taken from the same lesion or location thereafter.  Scar tissue from 
previous biopsies should be avoided.  A 4.5 mm punch biopsy should be taken from the most 
involved chronic active erythematous, scaly lesions.  For NLS, a 4.5 mm sample should be 
collected from the most normal appearing skin in a relative proximity to the LS biopsy site, at 
least 5 cm away from the lesion (at least 1 cm away, if 5 cm is not possible).  Full details of 
sample collection, processing and storage will be outlined in a separate lab manual. 
12.3.3.6. RT-PCR  
Skin biopsy samples, as collected and mentioned previously will also be used for RT-PCR.  The 
detailed methodology will be outlined in the lab manual. 
12.3.3.7. Serum Soluble OX40 Ligand and Serum Soluble OX40 
The PK samples will be used for the estimation of soluble OX40L and sOX40 in serum at the 
time points specified in the schedule of events in Appendix 1. The samples will be shipped to the 
specified bioanalytical lab.  Serum concentrations of soluble OX40 L and OX40 will be 
quantified using a qualified commercial ELISA kit. 
12.3.4. 
Pharmacogenomic Assessments 
Not applicable. 
12.4. 
Safety Assessments 
Safety assessments will consist of monitoring and recording all AEs and SAEs; regular 
monitoring of hematology, blood chemistry, and urinary laboratory values; periodic 
measurement of vital signs and ECGs; and performance of physical examinations as detailed in 
the Schedule of Events (Appendix 1).  At the end of the study another clinical assessment 
consisting of a physical examination and all laboratory tests performed at the time of screening 
(except viral serology, and FSH) will be performed.  Dosing will be based on evaluations 
performed by physicians/Investigator.  Additional assessments can be integrated into the protocol 
further to investigator judgment. 
12.4.1. 
Study Stopping Rules and Follow-up Criteria 
See Section 9.3. 
12.4.2. 
Adverse Events  
The Investigator or site staff will be responsible for detecting, documenting, and reporting events 
that meet the definition of an AE or SAE. 

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12.4.2.1. Assessment of Adverse Event 
The Reference Safety Information for this study is the IB section on Guidance for Investigators, 
Undesirable Effects. 
12.4.2.2. Adverse Events 
An AE is defined as any untoward medical occurrence in a patient administered IP 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 
(new or exacerbated) temporally associated with the use of an Investigational Product (IP), 
whether or not related to the IP.  An AE includes any event, regardless of the presumed causality 
between the event and the IP.   
Events that, while not necessarily meeting the definition of AEs, should be treated as such 
because they may be reportable to Regulatory Authorities according to AE reporting regulations, 
whether or not considered causally associated with IP, include the following: 
• IP overdose, whether accidental or intentional 
• IP abuse 
• An event occurring from IP withdrawal 
• Any failure of expected pharmacological action 
• Inadvertent or accidental IP exposure (e.g., product leaking or being spilled onto a 
patient or care-giver) 
• Unexpected therapeutic or clinical benefit from the IP  
• Medication errors (i.e., incorrect route of administration, incorrect dosage, use of 
incorrect product).   
Events that do not meet the definition of an AE include: 
• Medical or surgical procedure (e.g., endoscopy, appendectomy); the condition that 
leads to the procedure is an AE 
• Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital) 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the patient’s 
condition. 

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12.4.2.3. Assessment of Severity of Adverse Events 
The severity of AEs is classified as follows: 
Mild:  
• The AE is a transient discomfort and does not interfere in a significant 
manner with the patient 
• The AE resolves spontaneously or may require minimal therapeutic 
intervention 
Moderate:  
• The AE produces limited impairment of function and may require therapeutic 
intervention 
• The AE produces no sequelae 
Severe:  
• The AE results in a marked impairment of function and may lead to 
temporary inability to resume usual life pattern 
• The AE produces sequelae, which require (prolonged) therapeutic 
intervention 
The criteria for assessing severity are different from those used for seriousness (see Serious 
Adverse Events [Section 12.4.3] for the definition of an SAE). 
12.4.2.4. Assessment of Relationship to Study Medication 
The relationship of AEs to study medication is classified as follows: 
Not Related: 
A causal relationship between the study treatment and the AE is not a 
reasonable possibility 
Related: 
A causal relationship between the study treatment and the AE is a reasonable 
possibility  
Items to be considered when assessing the relationship of an AE to the study treatment are: 
• Temporal relationship of the onset of the event to the initiation of the study treatment 
• The course of the event, especially the effect of discontinuation of study treatment or 
reintroduction of study treatment, as applicable 
• Whether the event is known to be associated with the study treatment or with other 
similar treatments 
• The presence of risk factors in the study patient known to increase the occurrence of 
the event 

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• The presence of non-study treatment-related factors that are known to be associated 
with the occurrence of the event. 
For each adverse event, the Investigator should answer the following question with Yes or No: 
• Was there a reasonable possibility (evidence) that the drug caused the adverse event?  
A reasonable possibility means that there are facts (evidence) or arguments to suggest a causal 
relationship. 
NOTE: For patients that have not started receiving study medication the answer must be no. 
12.4.3. 
Serious Adverse Events  
A serious adverse event (SAE) is any untoward medical occurrence that, at any dose: 
• Results in death 
• Is life-threatening 
NOTE: The term 'life-threatening' in the definition of 'serious' refers to an event in 
which the patient was at risk of death at the time of the event.  It does not refer to an 
event, which hypothetically might have caused death, if it were more severe. 
• Requires hospitalization or prolongation of existing hospitalization 
NOTE: In general, hospitalization signifies that the patient has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or outpatient setting.  Complications that occur during hospitalization are AEs.  
If a complication prolongs hospitalization or fulfills any other serious criteria, the 
event is serious.  When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious.  Hospitalization for elective 
treatment of a pre-existing condition that did not worsen from baseline is not 
considered an AE. 
• Results in disability/incapacity 
NOTE: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions.  This definition is not intended to include experiences 
of relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma (e.g., sprained ankle) that may 
interfere or prevent everyday life functions but do not constitute a substantial 
disruption. 
• Is a congenital anomaly/birth defect 
• Medical or scientific judgment should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize 
the patient or may require medical or surgical intervention to prevent one of the other 

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outcomes listed in the above definition.  These should also be considered serious.  
Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse. 
12.4.3.1. Regulatory Reporting Requirements for SAEs 
Prompt notification of SAEs by the Investigator to Glenmark is essential so that legal obligations 
and ethical responsibilities towards the safety of patients are met. 
Glenmark has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a product under clinical investigation.  Glenmark will 
comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/ IEC and Investigators. 
All SAEs must be reported to the Sponsor immediately or within 24 hours of the Investigator or 
their staff becoming aware of them.  Reporting should be performed by recording as much 
information as is available at the time on the Serious Adverse Event Form and sending it to the 
contact information provided below:  
Fax:  + 44 1923 251137 
Email:  GlobalClinicalSAE@glenmarkpharma.com 
When further information becomes available, the Serious Adverse Event Form should be 
updated with the new information and reported immediately via the same contact information.  
Follow-up reports must be submitted to the Sponsor until the event resolves, the event stabilizes 
or the event returns to baseline if a baseline value is available. 
Additional information will be requested by the Sponsor as necessary. 
12.4.4. 
Pregnancy 
Any patient who has a positive pregnancy test after signing informed consent should be 
withdrawn from the study immediately and study medication should be discontinued 
immediately. 
Any pregnancy that occurs during study participation must be reported to the Sponsor, using a 
clinical trial pregnancy report form, immediately or within 24 hours of the Investigator learning 
of its occurrence.  The report should contain as much information as possible and should be sent 
to:  
Fax:  + 44 1923 251137 
Email:  GlobalClinicalSAE@glenmarkpharma.com 
When further information becomes available, the Pregnancy Report Form should be updated 
with all new information and reported immediately via the same contact information above.  The 

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pregnancy must be followed up to determine outcome (including premature termination) and 
status of mother and child, and this information must be sent to the Sponsor as above.  Pregnancy 
complications and elective terminations for medical reasons must be reported as an AE or SAE.  
Spontaneous abortions must be reported as an SAE.  Note: Pregnancy in itself will not be 
considered as an AE or SAE. 
Additional information will be requested by the Sponsor as necessary. 
Any SAE occurring in association with a pregnancy brought to the Investigator’s attention after 
the patient has completed the study and considered by the Investigator as possibly related to the 
investigational product, must be promptly reported to the Sponsor. 
The Investigator will attempt to collect pregnancy information on any female partner of a male 
study patient who becomes pregnant while participating in this study.  The Investigator will 
record pregnancy information on the appropriate form and submit it to the Sponsor within 
1 week of learning of the partner’s pregnancy.  The partner will also be followed to determine 
the outcome of the pregnancy.  Information on the status of the mother and child will be 
forwarded to the Sponsor.  Generally, follow-up will be no longer than 6 to 8 weeks following 
the estimated delivery date.  Any premature termination of the pregnancy will be reported. 
12.4.5. 
Collection and Recording of AEs and SAEs 
12.4.5.1. Collection of AEs 
The Investigator or site staff is responsible for detecting, documenting and reporting events that 
meet the definition of an AE or SAE. 
AEs will be collected from the time of signing the informed consent form until the follow up 
contact. 
SAEs will be collected over the same time period as stated above for AEs.  However, any SAEs 
assessed as related to study participation (e.g., IP, protocol mandated procedures, invasive tests, 
or change in existing therapy) or related to a concomitant medication that is a  Sponsor product, 
will be recorded from the time a patient consents to participate in the study up to and including 
any follow up contact.  All SAEs will be reported to the Sponsor within 24 hours, as indicated in 
Section 12.4.3.1. 
The Investigator will enquire about the occurrence of AEs/SAEs at every visit throughout the 
study (including Follow-up and Early Withdrawal visits where applicable), by asking the 
following non-leading verbal question of the patient (or care-giver, where appropriate): 
• “Have you had any medical problems since your last visit?” 
All Adverse Events not resolved by the end of the study or that have not resolved upon the 
patient’s discontinuation in the study must be followed until the event resolves, the event 
stabilizes or the event returns to baseline if a baseline value is available. 

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12.4.5.2. Recording of AEs 
All adverse events regardless of the seriousness, severity or relationship to the study medication 
must be recorded on the Adverse Events pages of eCRF.   
Adverse events that meet the definition of a serious adverse event must be reported on the 
Serious Adverse Event Form provided for this study. 
Adverse events must be documented in clear, unambiguous medical language.  Do not use 
abbreviations or acronyms.   
For each adverse event record only the diagnosis, do not report the characteristic signs and 
symptoms of the diagnosis as additional adverse events.   
If a diagnosis is not available record each sign and symptom as an adverse event, when a 
diagnosis becomes available, update the Adverse Event Case Record Form, to record the relevant 
diagnosis only. 
In general abnormal findings at screening should be recorded in the patient’s Medical History or 
in the Adverse Event section of eCRF.  However if, in the Investigators opinion, the finding is 
clinically significant and represents a condition that was not present at signing of informed 
consent, then the finding must be reported as an adverse event. 
12.4.6. 
Clinical Laboratory Tests 
Samples for clinical laboratory tests including hematology, chemistry, serology and urinalysis, 
will be taken after subjects have fasted for 4 hours and are summarized in Appendix 2. 
Patients should be in a seated or supine position during blood collection.  The Schedule of 
Events (Appendix 1) shows the visits and time points at which blood for clinical laboratory tests 
and urine for urinalysis will be collected in the study. 
A central laboratory will be used to measure laboratory parameters that are to be assessed as part 
of the safety analyses for the CSR and to qualify patients for entry into the study.  Local 
laboratories may be used in cases of a safety concern during the study, in which case the blood 
sample would be split (or 2 samples collected) to allow both a local laboratory and a central 
laboratory analysis.  In such cases, the local laboratory result(s) will be considered part of the 
source documentation only and the central laboratory result will be entered into the clinical 
database.  Local laboratory reports from non-split samples generated to follow safety concerns 
will be contained in the source documentation.   
12.4.6.1. Laboratory and Other Safety Assessment Abnormalities Reported as AEs and 
SAEs 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (e.g., ECGs, radiological scans, vital signs measurements), including those 
that worsen from baseline, and considered to be clinically significant in the medical and 
scientific judgment of the Investigator are to be recorded as AEs or SAEs. 

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However, any clinically significant safety assessments that are associated with the underlying 
disease, unless judged by the Investigator to be more severe than expected for the patient’s 
condition, are not to be reported as AEs or SAEs. 
12.4.7. 
Vital Signs 
Vital sign measurements (i.e., systolic and diastolic blood pressure [BP] [mmHg], pulse [beats 
per minute], body temperature [in centigrade]) will be obtained at the visits designated on the 
Schedule of Events (Appendix 1) by a validated method.  Supine or semi-supine blood pressure 
and pulse will be measured after the patient has been resting for at least 5 minutes.  All BP 
measurements should be performed on the same arm.  At the same time, patients will be asked 
about their well-being, and this will also be recorded.   In the event of detection of any 
abnormality during measurement of vital signs, the Investigator or his designate must be 
consulted for necessary action, which will be recorded.   
12.4.8. 
Physical Examination 
Physical examinations will be performed as designated on the Schedule of Events (Appendix 1).  
An abbreviated physical examination will be performed at all time-points except for screening 
where a full physical examination will be performed, as mentioned in Section 12.1.2.  Brief 
clinical examination of the patient will be conducted by a qualified medical designate on duty, 
and as defined in the Appendix 1 of the protocol.  Patient’s height will be measured at screening 
only.  In the event of detection of any abnormality during clinical examination, the Clinical 
Investigator must be consulted for necessary action, which will be recorded.  Documentation of 
the physical examination will be included in the physical examination section of the eCRF.  Only 
changes from screening physical examination findings that meet the definition of an AE will be 
recorded on the AEs CRF. 
12.4.9. 
ECG 
Supine 12-lead electrocardiograms will be obtained as designated on the Schedule of Events 
(Appendix 1), and as per methods mentioned in the relevant SOPs and appropriate instrument 
user manuals.  Patients must be in the supine position for a period of five minutes prior to the 
ECG.   
A physician will have to perform a clinical assessment of each 12-lead ECG.  PR, QT and QTc 
intervals, QRS duration and heart rate will be recorded.  The QT interval will be corrected for 
heart rate (QTc) using Frederica’s formula.  A copy of the ECG tracing has to be stored as source 
data.  Any clinically significant abnormality detected by the physician will be followed by 
triplicate ECGs. 
An ECG abnormality may meet the criteria of an AE as described in this protocol (see AEs 
[Section 12.4.2]) and the eCRF Completion Guidelines.  In these instances, the AE 
corresponding to the ECG abnormality will be recorded on the AEs CRF. 

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For ECG abnormalities meeting criteria of an SAE (see SAEs [Section 12.4.3]), the site must fax 
or email the SAE report including the ECG report to the Sponsor using the SAE form (see 
Regulatory Reporting Requirements for SAEs [Section 12.4.3.1]). 
12.4.10. 
Infusion Reactions 
Infusion reactions will be characterized as either acute or delayed.  Any infusion reaction 
occurring within 24 hours of drug infusion will be considered an acute reaction and any reaction 
occurring from 24 hours to 14 days following the drug infusion will be considered a delayed 
infusion reaction.  Both types of reaction will be further characterized depending on the severity 
of accompanying signs and symptoms as Grade 1 to 5 as classified by Common terminology 
criteria for adverse events (CTCAE) Version 4.03. 
Vital signs (temperature, pulse and blood pressure -systolic and diastolic) will be recorded prior 
to and every 30 minutes during the infusion.  The patients should be stabilized prior to 
discharging from study site.  During the infusion, patients will be monitored for the signs and 
symptoms of acute infusion reactions.  In the event of an infusion reaction, the rate of infusion 
may be decreased and the duration extended at the Investigator’s discretion, for patient safety.  
Staff trained in emergency care treatment and a facility equipped with emergency set that is 
readily available in the room where subjects are being dosed should be utilized for the study.  
Systemic hypersensitivity reactions will be managed according to treatment protocols that are in 
effect at the investigational site.  In the absence of such a protocol, the Mount Sinai protocol for 
management of infusion reactions can be used. 
12.4.11. 
Confirmation of Medical Care by Another Physician 
The Investigator will instruct patients to inform site personnel when they are planning to receive 
medical care by another physician.  At each visit, the Investigator/study coordinator will ask the 
patient whether he/she has received medical care by another physician since the last visit or is 
planning to do so in the future.  When the patient is going to receive medical care by another 
physician, the Investigator/study coordinator, with the consent of the patient, will inform the 
other physician that the patient is participating in the clinical study. 
13. 
DATA ANALYSIS AND STATISTICAL METHODS 
The statistical analysis will be coordinated by Glenmark.  A Statistical Analysis Plan (SAP) will 
be written to provide details of the analysis, along with specifications for tables, listings, and 
figures to be produced.  The SAP will be finalized prior to the database lock at the latest.  Any 
changes from the analyses planned in the SAP will be justified in the CSR. 
All analyses will be performed using SAS® Version 9.1.3 or above. 
Prior to database lock, a final blinded data review meeting will be held to allow a review of the 
clinical study data and to verify the data that will be used for analysis set classification.  A 
meeting to determine analysis set classifications may also be held prior to database lock. 

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In general, all data will be summarized with descriptive statistics (number of patients, mean, 
standard deviation, minimum, median and maximum) for continuous endpoints, and frequency 
and percentage for categorical endpoints. 
The results of the study will be reported in CSR in accordance with the ICH guidance.  Glenmark 
or delegate will prepare an integrated clinical and PK report.   
13.1.1. 
Sample Size  
No formal sample size calculation will be performed for this study.  The sample size chosen is 
based on experience from previous studies of similar nature.  Patients who are permanently 
discontinued from study drug due to reasons other than an AE and before the first post baseline 
skin biopsies (Visit 7) or before receiving two doses of study drug (Visit 7), will not be 
considered evaluable for the Biological Analysis Set (see Section 13.2).  The sample size of 60 to 
80 adult patients with AD randomized in ratio of 3: 1 (GBR 830 vs placebo) with approximately 
40 evaluable patients is considered to be sufficient to provide descriptive information on the PK, 
safety, tolerability and potential efficacy of GBR 830. 
A patient will be considered evaluable if he/she completes the Day 29 visit and has at least one 
post-baseline skin biopsy (Visit 7) and received two doses of study drug (Visit 7). 
Details of analyses will be specified in the SAP. 
13.2. 
Analysis Sets 
Detailed criteria for analysis sets will be documented in the SAP and the allocation of patients to 
analysis sets will be determined prior to database hard-lock. 
Full Analysis Set (FAS) 
The Full Analysis Set (FAS) will consist of all patients who are randomized and received at least 
1 dose of study drug.   
Biological Activity Set (BAS) 
The Biological Activity Set (BAS) will consist of all FAS patients who have at least one post-
baseline skin biopsy (Visit 7), and received 2 doses of study drug.  The primary analyses on 
biomarkers of disease activity obtained from biopsy will be based on the BAS. 
Safety Analysis Set (SAF) 
The Safety Analysis Set (SAF) consists of all patients who took at least 1 dose of study 
medication, and will be used for safety analyses.   
Pharmacokinetic Analysis Set (PKAS) 
The Pharmacokinetic Analysis Set (PKAS) consists of the subset of the SAF population for 
which sufficient serum concentration data is available to facilitate derivation of at least 1 PK 
parameter and for whom the time of dosing on the day of sampling is known.  Additional 
patients may be excluded from the PKAS at the discretion of the pharmacokineticist.  Any 

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formal definitions for exclusion of patients or time-points from the PKAS will be documented in 
the SAP. 
13.3. 
Patient Disposition 
Data on patient disposition (number of patients enrolled, number of drop-outs, and reasons for 
drop-out), demographics (gender, age, height, weight, BMI), and other baseline characteristics 
will be summarized.  The safety, tolerability, PK, and other data from each part of the study will 
be listed and summarized descriptively.  The number (percentage) of patients who were screened 
for the study (Enrolled Patients, i.e., those who signed informed consent) and reasons for screen 
failure will be described. 
13.4. 
Demographic and Other Baseline Characteristics 
Demographics and other baseline characteristics will be summarized by treatment group.  
Descriptive statistics will include number of patients, mean, standard deviation, minimum, 
median and maximum for continuous variables, and frequency and percentage for categorical 
variables.  Continuous demographic and baseline variables include age, height and body weight, 
and BMI; categorical variables include gender, race, and ethnicity.   
13.5. 
Efficacy Analyses 
Analysis will be conducted on the FAS, except biomarkers of disease activity obtained from 
biopsy will be based on the BAS.   
13.5.1. 
Analysis of Primary Efficacy Endpoint(s) 
13.5.1.1. Primary Analysis 
Expression of mRNA from skin biopsies will be analyzed using a mixed model with treatment 
and time as the fixed effects, and using the relevant baseline value as a covariate.  Differences 
between treatment groups and confidence intervals will be estimated.  Summary statistics of the 
mRNA expression will be provided for baseline, post-baseline, and change from baseline by 
treatment.   
13.5.2. 
Analysis of Secondary Efficacy Endpoint(s) 
Categorical analyses will be performed on responders (e.g., percentage of patients with 
responding rates of 50% at the end of weeks 8 and 12).  Comparisons between GBR 830 
treatment and placebo groups will be done using a Cochran-Mantel-Haenszel test.  For a patient, 
the efficacy data will be set to missing after prohibited medication is used.  The last observation 
carried forward (LOCF) method will be used to impute missing values. 

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13.5.3. 
Analysis of Exploratory Efficacy Endpoint(s) 
All exploratory efficacy analyses will be performed on the BAS for samples obtained from 
biopsy and FAS for samples not obtained from biopsy, and no multiplicity adjustment is planned.  
Analyses of exploratory endpoints will be provided in the SAP. 
13.6. 
Pharmacokinetic, Pharmacodynamic, Biomarker, and 
Pharmacogenomic/ Pharmacogenetic Analyses 
13.6.1. 
Pharmacokinetic Analyses 
Pharmacokinetic parameters will be summarized in tabular and graphic form.  Cmax, Tmax, 
AUC0-∞, AUC0-tau, and AUC0-t, will be estimated after the first and last dose administrations.  
Parameters like t1/2, volume of distribution, clearance and other relevant parameters may be 
assessed after the first and/or last dose administrations, if possible depending on the data. 
Pharmacokinetic parameters will be calculated using an appropriate software program.  Results 
of exploratory analyses will be summarized.  Details will be discussed in the SAP for this study. 
13.6.2. 
Immunogenicity Analyses 
Percentage of patients with positive and negative anti-drug antibody titers will be tabulated by 
treatment and time point.  The neutralizing antibody status would also be reported where 
applicable. 
13.6.3. 
Biomarker Analyses 
Informal exploratory biomarker analyses may be performed while the study is ongoing.  No one 
involved in the day-to-day conduct of the study will have access to biomarker data before the 
database is locked for this study.  The analysis of biomarker data will not impact any decisions 
regarding study conduct.  Exploratory efficacy analyses will be performed on the BAS for 
samples obtained from biopsy, and FAS for samples not obtained from biopsy, and no 
multiplicity adjustment is planned.  Analyses of exploratory endpoints will be provided in the 
SAP. 
13.7. 
Safety Analyses 
All safety analyses will be performed on the Safety Analysis Set. 
13.7.1. 
Extent of Exposure 
Approximately 60 to 80 adult patients with AD are planned to be randomized in a ratio of 3 
active: 1 placebo. 

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13.7.2. 
Adverse Events 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA).  The number and percentage of AEs, SAEs, AEs leading to discontinuation, and 
AEs related to investigational product will be summarized by system organ class, preferred term 
and treatment group.  Patients will be counted only once for each preferred term, system organ 
class, and by the highest severity of an event.  The number and percentage of AEs by severity 
will also be summarized.  All AEs will be displayed in listings.   
13.7.3. 
Laboratory Values 
For quantitative laboratory measurements descriptive statistics will be used to summarize results 
and change from baseline by treatment group and time point.  Shifts in laboratory tests relative to 
normal ranges from baseline to each time point during treatment will also be tabulated.  All 
laboratory data will be displayed in listings. 
13.7.4. 
Vital Signs 
Descriptive statistics will be used to summarize vital sign results and changes from baseline by 
treatment group and time.  Values of potential clinical significance will be tabulated.  All vital 
signs data will be displayed in listings. 
Shift tables will present changes from baseline (categorized as normal; abnormal, not clinically 
significant; and abnormal, clinically significant) to end of treatment (or end of phase or by visit). 
13.7.5. 
Electrocardiograms 
All ECG variables will be presented by visit.  Descriptive statistics for ECG parameters and 
changes from baseline will be presented by treatment group. 
Shift tables will present changes from baseline in ECG interpretation (categorized as normal; 
abnormal, not clinically significant; and abnormal, clinically significant) to end of treatment (or 
end of phase or by visit).   
13.7.6. 
Physical Examination 
Descriptive statistics will be used to summarize findings of potential clinical significance and 
will be listed. 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE 
The Sponsor or designee will implement and maintain quality assurance and quality control 
systems with Standard Operating Procedures (SOP) to ensure that this clinical study is conducted 
and data are generated, documented (recorded) and reported in compliance to the protocol, GCP 
standards, ICH and other applicable local regulations. 

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The Sponsor is responsible for securing agreement among collaborating parties to ensure direct 
access to clinical-study-related sites and material to ensure that all data are reliable and have 
been processed correctly. 
14.1. 
Procedures for Monitoring Compliance 
To ensure the completeness and accuracy of case report forms, the study will be monitored by a 
designated Clinical Trial Monitor (CTM).  At regular intervals the study monitor will visit the 
study center(s), the frequency of which will vary depending on the recruitment rate.  The first 
monitoring visit will be conducted after the first few patients are enrolled.  It is the duty of the 
Investigator to provide open access to the monitor of all study related records at previously 
agreed times.  The Sponsor, IRB/IEC, and regulatory authorities shall have right to direct access 
to source data for verification.   
14.2. 
Inspection 
An inspection is defined as the act of a regulatory authority of conducting an official review of 
documents, facilities, records and any other resources that are deemed by the authorities to be 
related to the clinical study and that may be located at the site of the study, or at the Sponsors 
and or CRO facilities or any other establishments deemed appropriate by the regulatory 
authorities. 
14.3. 
Audit 
An audit is a systematic and independent review of study-related activities and documents to 
determine whether study-related activities were conducted and the data were accurately recorded 
and analyzed according to the protocol, SOPs, GCP, and the appropriate requirements. 
In conducting this study the Investigator accepts that the Sponsor, IRB/IEC or regulatory body 
may, at any time by appointment, conduct an audit of the study site. 
15. 
ETHICS 
15.1. 
Ethics Committee Approval 
The clinical study protocol, ICF, and any documents that are given to the study patients 
(questionnaires, diaries, etc.) must be reviewed and approved by an IRB or IEC constituted and 
functioning in accordance with Section 3 of ICH E6 (GCP) and any local regulations.  Any 
protocol amendment, or revision to the ICF or other documents used in the study, will be 
resubmitted to the IRB/IEC for review and approval.  Documentation of IRB/IEC compliance 
with ICH E6 and any local regulations regarding constitution and review conduct will be 
provided to the Sponsor. 
Any queries raised by the IRB/IEC in regard to the study will be provided in writing to the 
Investigator or Sponsor, depending on local regulatory obligations.  The Investigator or Sponsor, 

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depending on local regulatory obligations, will be responsible for providing answers and 
resolving all queries prior to study start.  
A signed letter of study approval from the IRB/IEC chairman must be sent to the Investigator or 
Sponsor, depending on local regulatory obligations, before study start and the release of any 
investigational product to the site by the Sponsor or its designee (ICH E6, Section 4.4).  If the 
IRB/IEC decides to suspend or terminate the study, the Investigator (or if regionally required, the 
head of the medical institution) will immediately send the notice of study suspension or 
termination by the IRB/IEC to the Investigator or Sponsor, depending on local regulatory 
obligations.   
Written approvals from the IRB/IEC and Regulatory Authority must be obtained before starting 
the informed consent process for the first patient at the site.  The IRB/IEC will also review the 
ICF and endorse it in writing. 
Study progress is to be reported to IRB/IECs annually (or as required) by the Investigator or 
Sponsor, depending on local regulatory obligations.  If the Investigator is required to report to 
the IRB/IEC, he/she will forward a copy to the Sponsor at the time of each periodic report.  The 
Investigator(s) or the Sponsor will submit, depending on local regulations, periodic reports and 
inform the IRB/IECs (or if regionally required, the Investigator and the relevant IRB/IEC via the 
head of the medical institution) of any reportable AEs per ICH guidelines and local IRB/IEC 
standards of practice.  Upon completion of the study, the Investigator will provide the IRB/IECs 
with a brief report of the outcome of the study, if required. 
At the end of the study, the Investigator or Sponsor should notify the IRB/IEC and Regulatory 
Authority in accordance with local regulatory obligations.  The end of the study will be the date 
of the last study visit for the last patient in the study.  The Investigator or Sponsor, depending on 
local regulatory obligations, should also provide the IEC/IRB with a summary of the study’s 
outcome. 
In the case of early termination/temporary halt of the study, the Investigator or Sponsor should 
notify the IRB/IEC and Regulatory Authority in accordance with applicable regulatory 
requirements, and a detailed written explanation of the reasons for the termination/halt should be 
given. 
15.2. 
Ethical Conduct of the Study 
This study will be conducted in accordance with SOPs of the Sponsor (or designee), which are 
designed to ensure adherence to GCP guidelines as required by the following: 
• The ethical principles that have their origin in the World Medical Association 
(WMA) Declaration of Helsinki, adopted by the 18th WMA General Assembly, 
Helsinki, Finland, June 1964, and subsequent amendments. 
• ICH E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the 
Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, 
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• Title 21 of the United States Code of Federal Regulations (US 21 CFR) regarding 
clinical studies, including Part 50 and Part 56 concerning informed patient consent 
and IRB/IEC regulations and applicable sections of US 21 CFR Part 312 
• The regulations in the Food and Drug act in Health Canada 
• A waiver from the [IRB(s)/IEC(s)] will be obtained before study initiation for non-US 
studies conducted under an Investigational New Drug (IND) application. 
15.3. 
Informed Consent Process 
The Investigator is responsible for obtaining informed consent from each patient/legally 
acceptable representative (LAR) participating in the study.  All pertinent aspects of the study 
must be explained to the patient/LAR before he or she signs the informed consent.  Informed 
consent must be obtained from the patient/LAR before any activity or treatment is undertaken 
which is not part of routine care.  This includes, but is not limited to, the performance of 
diagnostic or therapeutic procedures and the administration of the first dose of the study 
medication.  Each patient must be informed that participation in the study is voluntary, that 
he/she may withdraw from the study at any time, and that withdrawal of consent will not affect 
his/her subsequent medical treatment or relationship with the treating physician. 
This informed consent should be given by means of a standard written statement, written in 
nontechnical language.  The patient/LAR should understand the statement before signing and 
dating it and will be given a copy of the signed document.   
Each patient must sign an approved ICF before study participation.  The form must be signed 
and dated by the appropriate parties.  The original, signed ICF for each patient will be verified by 
the Sponsor or designee and kept on file according to local procedures at the site.   
The patient or the patient’s LAR should be informed in a timely manner if new information 
becomes available that may be relevant to the patient’s willingness to continue participation in 
the study.  The communication of this information should be documented.  If required, informed 
consent should be obtained using an amended ICF for the patient’s continuation in the study. 
15.4. 
Approval of the Protocol and Amendments 
Patients will not be admitted to the study before approval of the study protocol and other relevant 
study documents by the IRB/IEC and Regulatory Authority. 
Any change or addition to this protocol requires a written protocol amendment that must be 
approved by the Sponsor, Principal Investigator and IRB/IEC before implementation.  
Amendments significantly affecting the safety of patients, the scope of the investigation or the 
scientific quality of the study will require additional approval by the IRB/IEC and the Regulatory 
Authority. 
These requirements for approval will in no way prevent any immediate action from being taken 
by the Principal Investigator in the interests of preserving the safety of the patients included in 

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the study.  If an immediate change to the protocol is felt necessary by the Principal Investigator 
and is implemented for safety reasons the IRB/IEC will be informed within 15 working days.   
Protocol amendments that affect only administrative aspects of the study may not require 
submission to Health or Regulatory Authority.  However, the IRB/IEC, according to local 
obligations will either approve all amendments to the protocol or will be notified of all the 
changes.  In these cases, the Investigator will inform the IEC of such changes. 
15.5. 
Protocol Deviation 
Any deviation from the protocol will be recorded as a protocol deviation. 
16. 
DATA HANDLING AND RECORD KEEPING 
16.1. 
Data Management 
Data from the study will be managed by Glenmark Pharmaceuticals Ltd or their representative.  
A copy of the study results will be made available to the clinical investigator for review. 
All data will be recorded on Electronic Case Report Forms (eCRFs).  The Investigator will allow 
representatives of the Sponsor, regulatory agencies, and their designees to inspect all study 
documents (including, but not limited to, consent forms, investigational product accountability 
forms, IRB/IEC approvals) and pertinent hospital or clinic records for confirmation of data 
throughout and after completion of the study.  Monitoring visits will be conducted as needed 
during the course of the study.  A complete review of source documentation of key efficacy and 
safety data will be conducted at each monitoring visit for verification that all information 
recorded in the CRF accurately reflects the data recorded in the patient's source documents.   
All data verification, using hospital or clinic records, will be performed respecting patient 
confidentiality and will be carried out in accordance with Standard Operating Procedures 
(SOPs).  An electronic copy of the study eCRF will be provided to the investigational site upon 
final query resolution and Database closure.   
All patient data generated during the study will be recorded and transcribed in the eCRF.  The 
Principal Investigator must approve the eCRF to confirm eligibility.  The final authorization of 
the CRF data is the Investigator Signature form.  This form must be approved by the Principal 
Investigator to signify that he/she has reviewed the eCRF, including all laboratory and safety 
assessments, and that all of the data therein is complete and accurate.   
The data will be reviewed to ensure that the forms were completed properly and that all data has 
the correct patient identification number throughout.   
16.2. 
Direct Access to Source Data/Documents 
Essential demographic data will be documented both within the patient’s hospital record notes 
(source data) and within the trial eCRF and be available for inspection by the Sponsor’s CTM.  

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Source data will also include date of consent, time of drug administration and blood sampling, 
together with vital signs recorded at each visit. 
It is the responsibility of the Investigator/s to maintain accurate and up to date records of all 
clinical study related activities, which should be entered on the eCRFs provided.  The source 
documents should be made available to the CTM on request, and in the event of a formal 
Investigator site audit. 
16.3. 
Confidentiality and Intellectual Property 
All information disclosed to the Investigator by the Sponsor or persons assigned by the Sponsor 
shall be treated by the Investigator as strictly confidential.  The Investigator shall only use such 
information for the purpose of conducting the clinical study described in this protocol and agrees 
not to disclose such information to any third party except those of his/her colleagues and 
employees who are assisting in the conduct of the study and who are bound by the obligations of 
confidentiality. 
Information concerning the investigational product, patent applications, processes, unpublished 
scientific data, the IB and other pertinent information is confidential and remains the property of 
the Sponsor.  Details should be disclosed only to the persons involved in the approval or conduct 
of the study.  The Investigator may use this information for the purpose of the study only.  It is 
understood by the Investigator that the Sponsor will use the information obtained during the 
clinical study in connection with the development of the drug and therefore may disclose it as 
required to other clinical Investigators or to regulatory agencies.  In order to allow for the use of 
the information derived from this clinical study, the Investigator understands that he has an 
obligation to provide the Sponsor with all data obtained during the study.  The Institution and/or 
the Investigator undertake that they will not reverse-engineer, decompile or dissemble the 
information or make any variant out of the information. 
All intellectual property arising out of, or in connection with, the conduct of the clinical study 
described in this protocol (“Derivative Intellectual Property”) shall be promptly disclosed to the 
Sponsor.  Any such Derivative Intellectual Property shall be the sole property of the Sponsor.  
The Institution and/or the Investigator, its affiliates and any person claiming through them shall 
do all acts and things as shall be necessary to vest all right, title and interest therein in the 
Sponsor.  The Institution and/or the Investigator shall keep the said Derivative Intellectual 
Property confidential in accordance with this Agreement. 
In the event of inconsistency between the above and the study contract, the terms of the study 
contract would prevail to the extent of such inconsistency. 
16.4. 
Record Retention 
On completion of the study electronic copies of all eCRFs (if generated) or the paper copies of 
the eCRF will be provided to the Investigator site for safekeeping for the duration stipulated by 
ICH GCP (currently 25 years or last marketing authorization, whichever is later).   

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17. 
FINANCING AND INSURANCE 
The Sponsor will provide insurance for any patients participating in the study in accordance with 
all applicable laws and regulations. 
18. 
PUBLICATION POLICY 
The Sponsor recognizes and supports the publication and dissemination of scientific information 
as a means of furthering knowledge.  The general strategy regarding publication of the study 
(e.g., what, when, where, etc.) will be mutually agreed upon by the Investigator and Sponsor.  
However, in order to protect its commercial interests, the Sponsor reserves the right to manage 
the publication of all study results.  The Investigator agrees that oral and written communication 
to third parties of any procedures or results from the study is patient to prior written consent of 
the Sponsor.  Presentation material and/or manuscript(s) for publication will be reviewed by 
Sponsor prior to submission for publication.  This review will be completed within 30 days of 
receiving presentation material and 60 days of receiving the manuscript from the Investigator.  
Alterations in the material will only be made in agreement between the Investigator and the 
Sponsor.   
In the event of inconsistency between the above and the study contract, the terms of the study 
contract would prevail to the extent of such inconsistency. 
19. 
DISCONTINUATION OF STUDY 
The Sponsor reserves the right to discontinue the study for medical reasons or any other reason at 
any time.  If a study is prematurely terminated or suspended, the Sponsor will promptly inform 
the Investigators/Institutions and regulatory authorities of the termination or suspension and the 
reason(s) for the termination or suspension.  The IRB/IEC will also be informed promptly and 
provided the reason(s) for the termination or suspension by the Sponsor or by the 
Investigator/Institution, as specified by the applicable regulatory requirement(s). 
The Investigator reserves the right to discontinue the study should his/her judgment so dictate.  If 
the Investigator terminates or suspends a study without prior agreement of the Sponsor, the 
Investigator should inform the Institution where applicable, and the Investigator/Institution 
should promptly inform the Sponsor and the IRB/IEC and provide the Sponsor and the IRB/IEC 
with a detailed written explanation of the termination or suspension.  Study records must be 
retained as noted above. 

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20. 
REFERENCES 
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for drug discovery.  Drug Discov Today 2009;14 (19/20):926-34. 
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Index 1994–2007: a comprehensive review of validation data and clinical results.  Br J 
Dermatol 2008;159:997-1035. 
3. Beck LA, Thaci D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al.  Dupilumab 
treatment in adults with moderate-to-severe atopic dermatitis.  N Engl J Med 
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4. Cooper GS, Stroehla BC.  The epidemiology of autoimmune diseases.  AutoImmun Rev 
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5. Croft M. Control of immunity by the TNFR-related molecule OX40 (CD134), Annu Rev 
Immunol 2010;28:57–78. 
6. Finlay AY, Khan GK.  Dermatology Life Quality Index (DLQI) --a simple practical 
measure for routine clinical use.  Clin Exp Dermatol 1994;19:210-6.  
7. Fujita H, Shemer A, Suarez-Farinas M, Johnson-Huang LM, Tintle S, Cardinale I, et al.  
Lesional dendritic cells in patients with chronic atopic dermatitis and psoriasis exhibit 
parallel ability to activate T-cell subsets.  J Allergy Clin Immunol 2011;128:574-82.  
8. Guttman-Yassky E, Nograles KE, Krueger JG.  Contrasting pathogenesis of atopic 
dermatitis and psoriasis—part I: clinical and pathologic concepts.  J Allergy Clin 
Immunol. 2011;127:1110–8. 
9. Guttman-Yassky E, Krueger JG.  Psoriasis: evolution of pathogenic concepts and new 
therapies through phases of translational research.  Br J Dermatol 2007;157:1103-15. 
10. Hanifin JM and Rajka G.  Diagnostic features of atopic dermatitis.  Acta Derm Venereol 
Suppl (Stockh) 1980;92:44-7. 
11. Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M.  The eczema area 
and severity index (EASI): assessment of reliability in atopic dermatitis.  EASI Evaluator 
Group.  Exp Dermatol 2001;10:11-18. 
12. Ito T, Wang YH, Duramad O, Hori T, Delespesse GJ, Watanabe N, et al.  TSLP-activated 
dendritic cells induce an inflammatory T helper type 2 cell response through OX40 
ligand.  J Exp Med 2005;202(9):1213-23.  
13. Hamilton JD, Suarez-Farinas M, Dhingra N, Cardinale I, Li X, Kostic A, et al.  
Dupilumab improves the molecular signature in skin of patients with moderate-to-severe 
atopic dermatitis.  J Allerg Clin Immunol 2014;134:1293-1300. 
http://dx.doi.org/10.1016/j.jaci.2014.10.013 

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14. Khattri S, Shemer A, Rozenblit M, Dhingra N, Czarnowicki T, Finney R, et al.  
Cyclosporine in patients with atopic dermatitis modulates activated inflammatory 
pathways and reverses epidermal pathology. J Allerg Clin Immunol 2014;133:1626-1634. 
http://dx.doi.org/10.1016/j.jaci.2014.03.003 
15. Kunz B, Oranje AP, Labreze L, Stalder JF, Ring J, Taieb A..  Clinical validation and 
guidelines for the SCORAD index: consensus report of the European Task Force on 
Atopic Dermatitis.  Dermatology 1997:195:10-9. 
16. Levin EC, Gupta R, Brown G, Malakouti M, Koo J.  Biologic fatigue in psoriasis.  J 
Dermatolog Treat 2014;25(1):78-82. 
17. Raap U, Weissmantel S, Gehring M, Wisenberg AM, Kapp A, Folster-Holst R.  IL-31 
significantly correlates with disease activity and Th2 cytokine levels in children with 
atopic dermatitis.  Pediatr Allergy Immunol 2012; 23:285–8. 
18. Ring J, Alomar A, Bieber T, Deleuran M, Fink-Wagner A, Gelmetti C, et al.  Guidelines 
for treatment of atopic eczema (atopic dermatitis) Part II. J  Eur   Dermatol Venereol 
2012;25:1176-93. 
19. Sidbury R, Davis DM, Cohen DE, Cordoro KM, Berger TG, Bergman JN, et al.  
Guidelines of care for the management of atopic dermatitis: section 3.  Management and 
treatment with phototherapy and systemic agents.  J Am Acad Dermatol 2014;71:327-49. 
20. Szegedi K, Kremer AE, Kezic S, Teunissen MB, Bos JD, Luiten RM, et al.  Increased 
frequencies of IL-31-producing T cells are found in chronic atopic dermatitis skin.  Exp 
Dermatol 2012;21:431–6. 
21. Wang YH and Liu YJ.  Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 
in allergic responses.  Clin Exp Allergy 2009;39:798–806. 
22. No authors listed.  Severity scoring of atopic dermatitis: the SCORAD index. Consensus 
Report of the European Task Force on Atopic Dermatitis.  Dermatology 1993;186:23-31. 

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APPENDIX 1. SCHEDULE OF EVENTS 
Visit1 
Screen-
ing 
Base-
line 
visit 
Follow-up visits 
Dosing 
visit 
Follow-up visits 
Study Day 
-30 to -1 
1 
4±1 
8±1 
15±1 
22±2 
29±1 
32±1 
36±1 
43±1 
50±2 
57±2 
71±2 
85±2 
Visit ID 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics (incl. height, weight and BMI)3 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
X 
Physical examination4 
X 
X 
 
 
X 
 
X 
 
 
X 
 
 
 
X 
TB testing5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG7 
X 
X 
X 
X 
 
 
X 
X 
X 
 
 
X 
X 
X 
Clinical laboratory8 
X 
X 
X 
X 
 
 
X 
X 
X 
 
 
X 
X 
X 
Drug and alcohol screen9 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
HBsAg, Anti-HBcAg, HCV and HIV tests 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy (females only)10 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Urine pregnancy (females only) 11 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
EASI, SCORAD, IGA, BSA 12,13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Whole body photography12 
 
X 
 
X 
 
 
 
 
 
X 
 
 
 
X 
DLQI, NRS 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Visit1 
Screen-
ing 
Base-
line 
visit 
Follow-up visits 
Dosing 
visit 
Follow-up visits 
Study Day 
-30 to -1 
1 
4±1 
8±1 
15±1 
22±2 
29±1 
32±1 
36±1 
43±1 
50±2 
57±2 
71±2 
85±2 
Visit ID 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Withdraw medication & dispense diary14 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomisation15 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study drug administration16 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
Previous and concomitant therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK sampling for GBR 83017 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Leukocyte sub-population cell counts, TEWL, 
total IgE, eosinophil 18 
 
X 
 
X 
X 
 
X 
 
X 
X 
 
X 
X 
X 
Cytokines and exploratory analysis18 
 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
Immunogenicity samples19 
 
X 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
Skin biopsies20 
 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
Adverse events21 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Phone call22 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
Appendix 1– Footnotes 
1. 
Visits do not include a Day 0. Visit 1 procedures may be conducted over more than 1 day as long as all tasks are completed within the allowable visit tolerance (at least 3 
days should be allowed for receipt of laboratory test results).  On visits patients should fast for at least 4 hours prior to safety sample collection.  The last assessments done 
prior to dosing will be considered as baseline.  The last follow-up visit on Day 85 will be considered the end-of study.  The end of study assessments will be done in place of 
visit procedures, for all patients receiving the study medication for all early withdrawal and dropouts.  Visits and assessments done in relation to the second infusion will be 
calculated from the actual day/start time of the second infusion. This applies to V8 to V11, inclusively. For V12, V13, and V14, the time points for assessment will be 672hr, 
1008hr, and 1344hr, respectively, from the start time of the second infusion. 
2. 
Medical history includes recent medical history (any illness occurring within past 4 weeks), previous medical history (only significant medical or surgical illness), smoking, 
alcohol and intake of drugs of abuse) 

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3. 
Demographics: includes date of birth, gender, race and ethnicity, height and body weight.  BMI will be calculated as weight (kg) / [height (m) x height (m)].  Only body 
weight will be repeated at subsequent visits.  Height measured at screening will be used for calculation of BMI at subsequent visits  
4. 
Physical examination: Comprehensive examination at screening and brief examination at all subsequent visits. 
5. 
TB testing: Patients must test negative for a QuantiFERON Gold-TB test done at screening; 
6. 
Vital signs: includes supine or semi-supine BP and pulse; and body temperature at screening, within 30 minutes before administration, 0.5 ± 10 mins during infusion, 1.0 ± 
10 mins, 2.0 ± 10 mins and 6.0 hours ± 10 mins estimated from the end time of the first infusion, and within 30 minutes before administration, 0.5 ± 10 mins during infusion, 
1.0 ± 10 mins, 2.0 ± 10 mins and 3.0 hours ± 10 mins estimated from the end time of the second infusion and at each follow-up visit.  Vitals have to be monitored every half 
hour during infusion. 
7. 
A single ECG will be taken at screening, at pre-dose, 2 ± 30 mins and 6 hours ± 30 mins estimated from the end time of the first infusion, at pre-dose, 2 ± 15 mins and 
3 hours ± 15 mins estimated from the end time of the second infusion, and on Day 4, Day 8, Day 32, Day 36, Day 57, Day 71 and on Day 85.  A triplicate ECG will be taken 
if there are any clinically significant abnormalities detected by the physician in single ECG. 
8. 
Clinical laboratory tests (labs) include hematology, biochemistry and urinalysis after a 4-hour fast.  Detailed panel mentioned in Appendix 2.  Labs will be done at 
screening, Day 1 (pre-dose), Day 4, Day 8, Day 29 (pre-dose), Day 32, Day 36, Day 57, Day 71 and Day 85.  Serum FSH and viral serology will be done 
only at screening. 
9. 
Drug and alcohol screen: alcohol or drugs of abuse at screening and before administration of each dose (pre-dose).  Drug screen includes amphetamines, BZD, barbiturates, 
cocaine, opioids, and cannabinoids. 
10. Serum pregnancy test for all women will be done during screening, Day 1 and at the end of study. 
11. Urine pregnancy test for all women will be done before administration of each dose (pre-dose).  Results of the pregnancy test should be negative before dispensing of study 
drug(s)  
12. Efficacy assessments will be done by a trained, blinded assessor.  The same assessor should do the assessments of a particular patient throughout the study. Assessments will 
be done at screening, at baseline (pre-dose on Day 1), at Days 4, 8, 15, 22, 29 (pre-dose), 32, 36, 43, 50, 57, 71, and 85.  If the patient signs for optional consent for 
photography, whole body photography (from neck down-anterior and posterior), will be taken, at baseline and at Days 8, 43, and 85. 
13. BSA will be done by the same assessor performing other efficacy assessment, and at similar time points. 
14. Patient must enter data into the diary every day from start of screening period to end of study visit.  Patient will be trained on the use of diary.  Patient will be instructed to 
enter the data every morning at a designated time and how to record them.   
15. Day of randomization and first dosing are assumed to be same, no waiver allowed.  Randomization schedule will be prepared using a centralized computer-based 
IVRS/IWRS system.   
16. IP administration: Continuous slow IV infusion for 60 min.  The infusion volume must be calculated using the patient’s current body weight.  The study site will contact 
patients by telephone approximately 24 hours after each infusion of IP.   
17. Serum samples for GBR-830 PK analysis will be obtained within 15 minutes before administration of each dose (pre-dose), immediately at the end of each infusion ± 10 
mins; at 1.5 ± 10 mins, 2 ± 10 mins, 4 ± 10 mins hours estimated from the start time of infusion, 72, 168, 336, 504 hours after each infusions; and on Day 57 (1344 hours), 71 
(1680 hours), and 85 (2016 hours) estimated from  the start time of  first infusion.  Visits and assessments done in relation to the second infusion will be calculated from the 
actual day/start time of the second infusion. This applies to V8 to V11, inclusively.  For V12, V13, and V14, the time points for assessment will be 672hr, 1008hr, and 
1344hr, respectively, from the start time of the second infusion. 
18. Leukocyte sub-population cell counts, TEWL, total IgE, eosinophil will be done on Day 1, 8, 15, 29, 36, 43, 57, 71, and 85.  Samples for TARC, eotaxin-3, and cytokine 
panel and additional exploratory analysis will be taken at baseline, at Day 29, and Day 71.  TEWL assessment is being performed by sites as per the TEWL manual and a 
predefined time point as per protocol will not be applicable. 
19. Samples will be collected for immunogenicity analysis at pre-dose, and at Day 15, (pre-dose) Day 29, Day 57, and Day 85.   
20. Skin biopsies will be taken at baseline at Day 29, and Day 71.   

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21. Adverse events will be reported as described and classified in the CTCAE version 4.03.  At each visit, the Investigator will ask the patient whether he/she has received 
medical care by another physician since the last visit or is planning to do so in the future. 
22. The site will contact the subject 24 hours after each infusion by phone. 
 

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APPENDIX 2. LIST OF CLINICAL LABORATORY TESTS 
The following tests will be performed.  Clinical evaluation of all clinical laboratory data will be 
performed by a qualified physician.  Reference range values from the central lab will be used for 
the tests mentioned below. 
HEMATOLOGY 
SERUM BIOCHEMISTRY 
• 
Hemoglobin  
• 
Hematocrit  
• 
White blood cell count  
• 
Differential white cell count  
• 
Red blood cell count with 
mean cell volume, mean cell 
hemoglobin, and mean cell 
hemoglobin concentration  
• 
Platelets 
 
Electrolytes 
• Sodium  
• Potassium  
• Calcium  
• Chloride  
• Bicarbonate  
 
Liver function tests 
• Total and direct 
 
bilirubin  
• Total protein  
• Globulin  
• Albumin  
• AST  
• ALT  
• GGT 
• ALP (Alkaline 
phosphatase) 
• Lactate dehydrogenase  
Renal function tests 
• Creatinine  
• Blood urea nitrogen (BUN) 
 
Other 
• Fasting blood sugar 
• Serum FSH (all women, 
 
only at screening) 
• Serum and urine Beta-
 
HCG (for females only) 
• Serum Immunoglobulins 
 
Lipid Profile  
• Total cholesterol  
• Triglycerides  
• HDL  
• LDL  
• VLDL 
URINALYSIS  
• 
pH 
• 
Specific gravity  
• 
Glucose  
• 
Protein  
• 
Ketones  
• 
Blood  
• 
Bilirubin 
• 
Leukocyte Esterase 
• 
Nitrite 
• 
Routine Microscopy  
SEROLOGY  
• 
Hepatitis B (HBsAg)  
• 
Anti-Hepatitis B Core (Anti-
HBcAg) 
• 
Hepatitis C antibody  
HIV 1 and 2 
OTHER 
• 
QuantiFERON Gold Blood TB Test  
• 
total IgE  
• 
circulating eosinophil counts 
 
 

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Table for Biopharmaeutics Analyses 
Serum GBR 830 
serum soluble OX40 ligand (sOX40L) 
Anti-drug antibodies 
serum soluble OX40 (sOX40) 
Table for Cytokine, Flow Cytometry and Biomarker Panels 
Cytokine and chemokine panel 
Serum cytokines and chemokines:  IL-22 (tested by Singulex), IL-13, CCL17 (TARC = thymus and activation-
regulated chemokine), Eotaxin (CCL11), TSLP, CXCL10 (IP-10), CCL2 (MCP-1), CCL20 (MIP3A),CCL22 
(MDC), CCL3 (MIP-1α), CCL4 (MIP-1β), CCL13 (MCP-4), CXCL11 (IP-9; I-TAC), and CXCL9 (MIG) (tested 
by OLINK multiplex panels). 
Antigen Marker(s) 
Cell Population Identified 
Single panel 
CD45RO -CD3 – CD4 – CD8 – OX40 – GBR830 – 
CD127 – CD25. 
Total T, T helper, Cytotoxic T, Tregs, Memory T cells 
IHC Panel (skin) & Skin thickness 
Skin thickness: Hematoxylin and Eosin staining 
Epidermal hyperplasia: Keratin 16 
Epidermal hyperplasia: Ki67 
Infiltrating T cells: CD3 and OX40 
High affinity IgE receptor; inflammatory dendritic cells: FcEpsilonRI; eosinophils; MBP 
Atopic DCs: OX40L 
RT-PCR panel (skin RNA), including at least but not limited to: 
hARP, K16, IL-13, IL-17A, IL-22, IFNg, OX40L, IL23p40, IL23p19 

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APPENDIX 3. NAME(S) OF CLINICAL LABORATORIES AND OTHER 
DEPARTMENTS AND/OR FACILITIES PARTICIPATING 
IN THE STUDY 
Clinical conduct and reporting 
Clinical laboratory 
Innovaderm Research Inc. 
1851, Sherbrooke St. East,  
Suite 502 
Montréal, QC H2K 4L5 
Canada 
Quintiles Laboratory, US 
 
Biopharmaceutical analysis 
Exploratory analysis 
Nuvisan GmbH 
Biopharmaceutics 
Wegenerstraße 13 
89231 Neu-Ulm 
Germany 
 
Icahn School of Medicine at Mount Sinai  
1425 Madison Avenue 
Icahn 13-76, New York, NY 10029 
 
 
 

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APPENDIX 4. SUMMARY OF CHANGES IN CURRENT PROTOCOL 
AMENDMENT 
 
 
 
PROTOCOL NUMBER: GBR 830-201 
PROTOCOL AMENDMENT 3.0 
SUMMARY OF CHANGES 
A Phase IIa, Double-Blind, Randomized, Placebo-controlled, 
Exploratory Study to Evaluate the Safety, Biological Activity and Pharmacokinetics  
of GBR 830 in Adult Patients With Moderate-to-Severe Atopic Dermatitis 
 
PROTOCOL HISTORY 
PROTOCOL VERSION 1.0, 12-Oct-2015 
PROTOCOL VERSION 2.0, 19-May-2016 
PROTOCOL VERSION 3.0, 07-Nov-2016 
PROTOCOL VERSION 4.0, 16-Feb-2017 
 
 
 
 
 
 
Description of Changes in Protocol Version 4.0 (Amendment 3.0) dated 16-Feb-2017 
Minor editorial changes for accuracy, clarity, and consistency and minor formatting changes 
have been made throughout the document and are not included in the description(s) below. 
 

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Key:  Bold: Newly added text 
           Strikethrough text: Deleted text from the previous version of the protocol.  
A. Details of Substantial Changes to the Protocol  
From 
Protocol Version 3.0  
(Amendment 2.0)  
07-Nov-2016 
To 
Protocol Version 4.0  
(Amendment 3.0)  
16-Feb-2017 
Rationale for 
Amendment 
1. Synopsis, Study Objective(s); Section 6.2, Secondary Objective(s) 
Used to read: 
 
Secondary: 
• Effect of GBR 830 on additional 
efficacy parameters in adult 
patients with AD. 
 
Now reads: 
 
Secondary: 
• Effect of GBR 830 on additional clinical 
efficacy parameters in adult patients with 
AD. 
 
Clarification that 
secondary efficacy 
parameters are clinical. 
2. Synopsis, Study Endpoint(s); Section 8.3, Exploratory Endpoint(s) 
Used to read:  
Exploratory: Change from baseline 
in levels of: 
• Cytokines in serum: Interleukin 
(IL)-13 and IL-22, Chemokine 
ligands (CCL) CCL2, CCL3, 
CCL4, CCL5, CCL18, CCL20, 
CCL22, CCL13, CXCL9, 
CXCL10, CXCL11 
• Leukocyte sub-population cell 
counts (Total T, T helper, 
Cytotoxic T, Tregs, Memory T 
cells, OX40 T cells, GBR 830 T 
cells). 
• Cellular infiltrates (T-cells, 
Dendritic cells) as assessed by 
CD3, FcEpsilon RI and OX40L. 
• Serum Thymus and activation-
regulated chemokine 
(TARC/CCL17), eotaxin-3, total 
Immunoglobulin E (IgE), and 
circulating eosinophil counts 
• Percentage OX40 receptor 
occupancy (RO) 
Now reads:  
Exploratory: Change from baseline in levels 
of: 
• Cytokines in serum: Interleukin (IL)-13 
and IL-22, Chemokine ligands (CCL) 
CCL2, CCL3, CCL4, CCL5, CCL18, 
CCL20, CCL22, CCL13, CXCL9, 
CXCL10, CXCL11  Cytokines and 
chemokines in serum: Interleukin 
(IL)-22, IL-13, chemokine ligand 
(CCL)-17 (TARC = thymus and 
activation-regulated chemokine), 
Eotaxin (CCL11), TSLP, CXCL10 
(IP-10),CCL2 (MCP-1), CCL20 
(MIP3A), CCL22 (MDC), CCL3 
(MIP-1α, CCL4 (MIP-1β), CCL13 
(MCP-4), CXCL11 (IP-9; I-TAC) and 
CXCL9 (MIG). 
• Leukocyte sub-population cell counts 
(Total T, T helper, Cytotoxic T, Tregs, 
Memory T cells, OX40 T cells, GBR 830 
T cells). 
• Cellular infiltrates (T-cells, dendritic 
cells) as assessed by CD3, FcEpsilon RI, 
and OX40L, OX40, and MBP. 
Revised to reflect actual 
biomarkers being 
analyzed based on 
update of the technical 
feasibility review 

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From 
Protocol Version 3.0  
(Amendment 2.0)  
07-Nov-2016 
To 
Protocol Version 4.0  
(Amendment 3.0)  
16-Feb-2017 
Rationale for 
Amendment 
• Serum thymus and activation-regulated 
chemokine (TARC/CCL17), eotaxin-3, 
total Immunoglobulin E (IgE), serum 
soluble OX40, serum soluble OX40 
ligand (sOX40L), and circulating 
eosinophil counts 
• Percentage OX40 receptor occupancy 
(RO) 
3. Synopsis, Biomarker Assessments 
Used to read:  
RO assay, cytokines, TEWL, TARC, 
eotaxin-3, total  IgE, eosinophil 
levels will also be measured in the 
study.   
Now reads:  
Leukocyte sub-population cell counts RO 
assay, cytokines, chemokines, TEWL, 
TARC, eotaxin-3, total IgE, sOX40L, and 
eosinophil levels will also be measured in the 
study.  Cellular infiltrates (T-cells, 
dendritic cells) will be assessed by 
immunohistochemistry of biopsy slides 
with CD3, FcEpsilon RI, OX40L, OX40, 
and MBP. 
Serum soluble OX40 and OX40L will be 
measured using PK samples at the time 
points defined in Appendix 1. 
 
Revised to reflect actual 
biomarkers being 
analyzed based on 
update of the technical 
feasibility review. 
Clarified that serum 
soluble OX40 and OX40 
ligand will be measured 
from PK blood samples 
taken. 
4. Section 11.2, Dosing visits (Visits 2 and 7); Section 11.4, Follow-up Visits 4 and 9 (Days 8±1 and 
36±1); Section 11.5, Follow-up Visits 5 and 10 (Days 15±1 and 43±1); Section 11.7, Follow-up Visits 12 
and 13 (Days 57±2 and 71±2); Section 11.8, Follow-up Visits (end of study) assessments on Day 85 
(±2); Appendix 1 Schedule of Events (table row and footnote 18) 
Used to read:  
• RO assay, TEWL, total IgE, 
eosinophil count 
Now reads: 
• RO assay, Leukocyte sub-population 
cell counts (Total T, T helper, Cytotoxic 
T, Tregs, Memory T cells), TEWL, total 
IgE, eosinophil count 
Revised to reflect actual 
biomarkers being 
analyzed based on 
update of the technical 
feasibility review.  
5. Section 12.3.3.1, title of section 
Used to read:  
12.3.3.1 Flow cytometry/ Receptor 
Occupancy assay 
Now reads:  
12.3.3.1 Flow cytometry/ Receptor 
Occupancy assay Leukocyte sub-
population cell counts 
Revised to reflect actual 
biomarkers being 
analyzed based on 
update of the technical 
feasibility review. 
6. Section 12.3.3.2, title of section 

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From 
Protocol Version 3.0  
(Amendment 2.0)  
07-Nov-2016 
To 
Protocol Version 4.0  
(Amendment 3.0)  
16-Feb-2017 
Rationale for 
Amendment 
Used to read:  
12.3.3.2 Cytokine 
Now reads:  
12.3.3.2 Cytokines and Chemokines 
  
Revised to reflect actual 
biomarkers being 
analyzed based on 
update of the technical 
feasibility review.  
7. Former Section 12.3.3.3, TARC (CCL17) 
Used to read: 
Thymus and activation-regulated 
chemokine is a chemokine, shown to 
be strongly associated with disease 
severity in AD, and may be involved 
in pathogenesis of the disease.  
Baseline TARC levels will be 
assessed for potential predictive 
value for treatment response.  Post-
treatment samples will be evaluated 
for effects of GBR 830 on TARC.  
Detailed instructions for blood 
sample collection will be outlined in 
a separate lab manual.  Blood 
samples will be collected at 
appropriate time points defined in 
Appendix 1. 
Section 12.3.3.3 deleted entirely 
Section 12.3.3.3, TARC (CCL17) 
Thymus and activation-regulated chemokine 
is a chemokine, shown to be strongly 
associated with disease severity in AD, and 
may be involved in pathogenesis of the 
disease.  Baseline TARC levels will be 
assessed for potential predictive value for 
treatment response.  Post-treatment samples 
will be evaluated for effects of GBR 830 on 
TARC.  Detailed instructions for blood 
sample collection will be outlined in a 
separate lab manual.  Blood samples will be 
collected at appropriate time points defined 
in Appendix 1. 
Deleting section 12.3.3.3 
since TARC is included 
in a previous section. 
8. Former Section 12.3.3.4, Eotaxin 3 (CCL26) 
Used to read: 
Eotaxin-3 is a chemokine, shown to 
be associated with disease severity in 
AD, and may be involved in 
pathogenesis of the disease.  Baseline 
eotaxin-3 levels will be assessed for 
potential predictive value for 
treatment response.  Post-treatment 
samples will be evaluated for effects 
of GBR 830 on eotaxin-3.  Detailed 
instructions for blood sample 
collection will be outlined in a 
separate lab manual.  Blood samples 
will be collected at appropriate time 
points defined in Appendix 1. 
Section 13.3.3.4 deleted entirely 
Section 12.3.3.4, Eotaxin 3 (CCL26) 
Eotaxin-3 is a chemokine, shown to be 
associated with disease severity in AD, and 
may be involved in pathogenesis of the 
disease.  Baseline eotaxin-3 levels will be 
assessed for potential predictive value for 
treatment response.  Post-treatment samples 
will be evaluated for effects of GBR 830 on 
eotaxin-3.  Detailed instructions for blood 
sample collection will be outlined in a 
separate lab manual.  Blood samples will be 
collected at appropriate time points defined 
in Appendix 1. 
 
Revised to reflect actual 
biomarkers being 
analyzed based on 
update of the technical 
feasibility review. 
(Eotaxin-3 will not be 
measured as it is not on 
the OLINK panels.) 

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From 
Protocol Version 3.0  
(Amendment 2.0)  
07-Nov-2016 
To 
Protocol Version 4.0  
(Amendment 3.0)  
16-Feb-2017 
Rationale for 
Amendment 
9. Section numbers 12.3.3.3, 12.3.3.4, 12.3.3.5 (formerly 12.3.3.5, 12.3.3.6, 12.3.3.7) 
Used to read: 
12.3.3.5 Total IgE 
12.3.3.6 Transepidermal Water Loss 
12.3.3.7 Immunohistochemistry 
(IHC) 
Now reads: 
12.3.3.512.3.3.3 Total IgE 
12.3.3.612.3.3.4 Transepidermal Water Loss 
12.3.3.712.3.3.5 Immunohistochemistry 
(IHC) 
Renumbering of 
subsections due to 
deletion of TARC and 
Eotaxin subsections 
above (see points 7 and 8 
in this table). 
10. Section 12.3.3.6 (formerly 12.3.3.8), RT-PCR 
Used to read: 
12.3.3.8, RT-PCR and gene 
microarray 
Skin biopsy samples, as collected 
and mentioned previously will also 
be used for RT-PCR.  The detailed 
methodology will be outlined in the 
lab manual. 
 
Now reads: 
12.3.3.6, RT-PCR and gene microarray 
Skin biopsy samples, as collected and 
mentioned previously will also be used for 
RT-PCR and gene microarray.  The detailed 
methodology will be outlined in the lab 
manual. 
 
Revised to reflect actual 
biomarkers being 
analyzed based on 
update of the technical 
feasibility review.  
11. Section 12.3.3.7, Serum Soluble OX40 Ligand and Serum Soluble OX40 
Used to read: 
(Section not applicable) 
New section 12.3.3.7 added: 
The PK samples will be used for the 
estimation of soluble OX40L and sOX40 
in serum at the time points specified in the 
schedule of events in Appendix 1. The 
samples will be shipped to the specified 
bioanalytical lab.  Serum concentrations 
of soluble OX40 L and OX40 will be 
quantified using a qualified commercial 
ELISA kit. 
 
Addition of serum 
soluble OX40 and serum 
soluble OX40L and 
clarification of when 
samples will be 
collected. 

GBR 830-201 
Version 4.0 
Date 16-Feb-2017 
Glenmark  
CONFIDENTIAL 
Page 92 of 98 
From 
Protocol Version 3.0  
(Amendment 2.0)  
07-Nov-2016 
To 
Protocol Version 4.0  
(Amendment 3.0)  
16-Feb-2017 
Rationale for 
Amendment 
12. Section 13.5.1.1, Primary Analysis 
Used to read:  
All continuous efficacy variables will 
be analyzed using an analysis of 
covariance (ANCOVA) model with 
treatment as the fixed effects, and 
using the relevant baseline value as a 
covariate. Differences between 
treatment groups and confidence 
intervals will be estimated within the 
framework of ANCOVA. In the 
event that the model assumptions are 
not warranted, the rank-based 
ANCOVA will be used. 
 
Now reads:  
All continuous efficacy variables Expression 
of mRNA from skin biopsies will be 
analyzed using an analysis of covariance 
(ANCOVA) a mixed model with treatment 
and time as the fixed effects, and using the 
relevant baseline value as a covariate.   
Differences between treatment groups and 
confidence intervals will be estimated within 
the framework of ANCOVA. In the event 
that the model assumptions are not 
warranted, the rank-based analysis of 
covariance (ANCOVA) will be used.  
Summary statistics of the mRNA 
expression will be provided for baseline, 
post-baseline, and change from baseline 
by treatment.   
Updated statistical 
methods to be used in 
the primary analysis, to 
better reflect the primary 
objectives. 
13. Section 13.5.2, Analysis of Secondary Efficacy Endpoint(s) 
Used to read: 
Categorical analyses will be 
performed on responders (e.g., 
percentage of patients with 
responding rates of 50% at the end of 
week 12). 
Now reads: 
Categorical analyses will be performed on 
responders (e.g., percentage of patients with 
responding rates of 50% at the end of weeks 
8 and 12). 
Clarification that 
analyses will be 
performed using both 
week 8 and week 12 
data. 
14. Appendix 2, List of Clinical Laboratory Tests 
Used to read: 
OTHER 
• QuantiFERON Gold Blood TB 
Test  
• Serum TARC 
• eotaxin-3  
• total IgE 
• circulating eosinophil counts 
Now reads: 
OTHER 
• 
QuantiFERON Gold Blood TB Test  
• 
Serum TARC 
• 
eotaxin-3  
• 
total IgE 
• 
circulating eosinophil counts 
Revised to reflect actual 
biomarkers being 
analyzed based on 
update of the technical 
feasibility review. 

GBR 830-201 
Version 4.0 
Date 16-Feb-2017 
Glenmark  
CONFIDENTIAL 
Page 93 of 98 
From 
Protocol Version 3.0  
(Amendment 2.0)  
07-Nov-2016 
To 
Protocol Version 4.0  
(Amendment 3.0)  
16-Feb-2017 
Rationale for 
Amendment 
15. Appendix 2, Table for Biopharmaceutic Analyses 
Used to read: 
(Table for Biopharmaceutic Analyses 
not applicable.) 
 
 
Added: 
Table for Biopharmaceutic Analyses 
• Serum GBR 830 
• Serum soluble OX40 ligand (sOX40L) 
• Anti-drug antibodies 
• Serum soluble OX40 (sOX40) 
 
  
Added sOX40L and 
sOX40. Clarification of 
testing to be performed 
by Biopharmaceutics 
Laboratory listed in 
Appendix 3. 
 
 
16. Appendix 2, Table for Cytokine, Flow Cytometry, and Biomarker Panels  
Used to read:  
Cytokine panel 
Serum Cytokines (IL-13, IL-22,  by 
singulex platform and a panel of 10 
Th1 and Th2 chemokines by MSD 
(CCL2, CCL3, CCL4, CCL5, 
CCL18, CCL20, CCL22, CCL13, 
CXCL9, CXCL10, CXCL11 
 
RO assay panel 
… 
Total T, T helper, Cytotoxic T, 
Tregs, Memory T cells, OX40 T 
cells, GBR 830 T cells 
… 
Infiltrating T cells: CD3  
High affinity IgE receptor; 
inflammatory dendritic cells: 
FcEpsilonRI 
. . . 
Gene microarray panel  
Affymetrix U133Plus 2 arrays 
 
RT-PCR panel (skin RNA) 
hARP, K16, IL-13, IL-17A, IL-22, 
IFNg, OX40L, IL23p40, IL23p19 
Now reads:  
Cytokine and chemokine panel 
Serum Cytokines (IL-13, IL-22,  by singulex 
platform and a panel of 10 Th1 and Th2 
chemokines by MSD (CCL2, CCL3, CCL4, 
CCL5, CCL18, CCL20, CCL22, CCL13, 
CXCL9, CXCL10, CXCL11 Serum 
cytokines and chemokines:  IL-22 (tested 
by Singulex), IL-13, CCL17 (TARC = 
thymus and activation-regulated 
chemokine), Eotaxin (CCL11), TSLP, 
CXCL10 (IP-10), CCL2 (MCP-1), CCL20 
(MIP3A),CCL22 (MDC), CCL3 (MIP-1α), 
CCL4 (MIP-1β), CCL13 (MCP-4), 
CXCL11 (IP-9; I-TAC), and CXCL9 
(MIG) (tested by OLINK multiplex 
panels) 
 
RO assay panel 
… 
Total T, T helper, Cytotoxic T, Tregs, 
Memory T cells, OX40 T cells, GBR 830 T 
cells 
… 
Infiltrating T cells: CD3 and OX40 
High affinity IgE receptor; inflammatory 
dendritic cells: FcEpsilonRI; eosinophils; 
MBP 
. . . 
Revised to reflect actual 
biomarkers being 
analyzed based on 
update of the technical 
feasibility review. 

GBR 830-201 
Version 4.0 
Date 16-Feb-2017 
Glenmark  
CONFIDENTIAL 
Page 94 of 98 
From 
Protocol Version 3.0  
(Amendment 2.0)  
07-Nov-2016 
To 
Protocol Version 4.0  
(Amendment 3.0)  
16-Feb-2017 
Rationale for 
Amendment 
Gene microarray panel  
Affymetrix U133Plus 2 arrays 
 
RT-PCR panel (skin RNA) , including at 
least but not limited to: 
hARP, K16, IL-13, IL-17A, IL-22, IFNg, 
OX40L, IL23p40, IL23p19 
 

GBR 830-201 
Version 4.0 
Date 16-Feb-2017 
Glenmark  
CONFIDENTIAL 
Page 95 of 98 
B. Details of Non-substantial Changes to the Protocol: 
From 
Protocol Version 3.0  
(Amendment 2.0)  
07-Nov-2016 
To 
Protocol Version 4.0  
(Amendment 3.0)  
16-Feb-2017 
Rationale for Amendment 
1. Section 7, Figure 2, Study Flow Chart; Section 11, Window for collection of samples for GBR-830 PK 
analysis, window for vital signs, window for ECG recording, For all other safety and 
pharmacodynamics/biomarker/immunogenicity assessments; Appendix 1, Schedule of Assessments 
(footnote 17) 
Used to read:  
If the second infusion time is altered, 
then the time-points for visits V12, 
V13 and V14 will be calculated from 
the second infusion. 
Now reads:  
If the second infusion time is altered, 
then the time-points for visits V12, V13 
and V14 will be calculated from the 
second infusion. Visits and 
assessments done in relation to the 
second infusion will be calculated 
from the actual day/start time of the 
second infusion.  This applies to V8 
to V11, inclusively.  For V12, V13, 
and V14, the time points for 
assessment will be 672hr, 1008hr, 
and 1344hr, respectively, from the 
start time of the second infusion. 
Clarification that assessments 
following the nomimal Day 29 
dose will be calculated from 
the actual day/start time of this 
second dose.    
2. Section 7.2, Discussion of Study Design, Including Choice of Control Groups 
Used to read: 
. . . Recently, improvements of the 
AD molecular signature were 
observed in patients after treatment 
with 4 weeks with cyclosporine and 
dupilumab Guttman-Yassky E et al; 
Hamilton et al, 2014), a targeted Th2 
antagonist, and these changes 
occurred earlier and were larger than 
clinical endpoints, suggesting that 
these are valid endpoints for an 
exploratory study. 
Now reads: 
 
. . . Recently, improvements of the AD 
molecular signature were observed in 
patients after treatment with 4 weeks 
with cyclosporine and dupilumab 
Guttman-Yassky E et al; Hamilton et 
al, 2014; Beck et al, 2014), a targeted 
Th2 antagonist, and these changes 
occurred earlier and were larger than 
clinical endpoints, suggesting that these 
are valid endpoints for an exploratory 
study. 
Correction of typographical 
error. 
3. Section 10.3, Allocation to Treatment Groups 
Used to read: 
• For patients randomized prior to 
amendment 3 who do not 
Now reads: 
• For patients randomized prior to 
protocol version 3 (amendment 
Correction of typographical 
error. 

GBR 830-201 
Version 4.0 
Date 16-Feb-2017 
Glenmark  
CONFIDENTIAL 
Page 96 of 98 
From 
Protocol Version 3.0  
(Amendment 2.0)  
07-Nov-2016 
To 
Protocol Version 4.0  
(Amendment 3.0)  
16-Feb-2017 
Rationale for Amendment 
complete at least the Day 29 
visit:  . . . 
• For patients randomized after 
amendment 3 who do not 
complete at least the Day 29 
visit: . . . 
32) who do not complete at least the 
Day 29 visit:  . . . 
• For patients randomized after 
protocol version 3 (amendment 
23) who do not complete at least the 
Day 29 visit: . . . 
 
4. Section 11.9, Early Withdrawal Visit 
Used to read: 
The Early Withdrawal Visit will be 
performed as applicable (see Section 
9.3.2 for additional information).  
The end of study assessments will be 
performed for all patients receiving 
study drugs who withdraw 
prematurely from the study.  Any 
patient who is withdrawn must be 
followed-up for approximately 
5 half-lives (56 days) after the last 
infusion. 
 
Now reads: 
The Early Withdrawal Visit will be 
performed as applicable (see Section 
9.3.2 for additional information).  The 
end of study assessments will be 
performed for all patients receiving 
study drugs who withdraw prematurely 
from the study.  Any patient who is 
withdrawn must be followed-up as 
outlined in Section 9.3 and in 
Appendix 1, but at least for 
approximately 5 half-lives (56 days) 
after the last infusion. 
 
Clarification of end of study 
assessments in the event a 
subject withdraws early from 
the study. 
5. Section 12.4.4, Pregnancy 
Used to read: 
Any pregnancy that occurs during 
study participation must be reported 
to the Sponsor, using a clinical trial 
pregnancy form, . . . 
Now reads: 
Any pregnancy that occurs during study 
participation must be reported to the 
Sponsor, using a clinical trial 
pregnancy report form, . . . 
Minor clarification of name of 
form. 

GBR 830-201 
Version 4.0 
Date 16-Feb-2017 
Glenmark  
CONFIDENTIAL 
Page 97 of 98 
From 
Protocol Version 3.0  
(Amendment 2.0)  
07-Nov-2016 
To 
Protocol Version 4.0  
(Amendment 3.0)  
16-Feb-2017 
Rationale for Amendment 
6. Section 13.6, Pharmacokinetic, Pharmacodynamic, Biomarker, and Pharmacogenomic/Pharmacogenetic 
Analyses 
Used to read: 
13.6 . . . 
13.6.1.1 . . . 
13.6.1.2 . . . 
13.6.1.3 . . . 
Now reads: 
13.6 . . . 
13.6.1  . . . 
13.6.2  . . . 
13.6.3 . . . 
Correction of typographical 
error in numbering 
subsections. 
7. Section 20, References 
Used to read: 
(References 1 – 22.) 
Reference 13: 
Jennifer et al. . . . 
 
Now reads: 
(References 1-22 updated to put into 
Vancouver style, cross-references fixed 
in document where applicable.) 
Reference 13: 
Hamilton JD, Suarez-Farinas M, 
Dhingra N, Cardinale I, Li X, Kostic A, 
et al.  . . . 
References 1-22 updated to 
put into Vancouver style. 
Cross-references fixed in 
document where applicable. 
Reference 13 corrected 
typographical error in first 
author name (Jennifer D. 
Hamilton). 
8. Appendix 1, Schedule of Assessments (footnote 1) 
Used to read: 
1. . . . Assessments done in relation to the 
second infusion will be calculated from 
the actual day of dosing.   
 
Now reads: 
1. Assessments done in relation to 
the second infusion will be 
calculated from the actual day of 
dosing. Visits and assessments 
done in relation to the second 
infusion will be calculated from 
the actual day/start time of the 
second infusion.  This applies to 
V8 to V11, inclusively.  For V12, 
V13, and V14, the time points for 
assessment will be 672hr, 1008hr, 
and 1344hr, respectively, from the 
start time of the second infusion. 
Clarification that assessments 
following the nomimal Day 29 
dose will be calculated from 
the actual day/start time of this 
second dose. 

GBR 830-201 
Version 4.0 
Date 16-Feb-2017 
Glenmark  
CONFIDENTIAL 
Page 98 of 98 
From 
Protocol Version 3.0  
(Amendment 2.0)  
07-Nov-2016 
To 
Protocol Version 4.0  
(Amendment 3.0)  
16-Feb-2017 
Rationale for Amendment 
9. Appendix 1, Schedule of Assessments (footnote 18) 
(Not applicable)  
Added to footnote 18:  
18. . . . TEWL assessment is being 
performed by sites as per the 
TEWL manual and a predefined 
time point as per protocol will 
not be applicable. 
Clarification that TEWL 
assessment is to be performed 
as per the TEWL manual. 
10. Appendix 4, title of appendix and contents 
Used to read:Appendix 4, GBR 830-
201 Protocol Amendment 2.0 
(contents reflecting protocol version 
3 [amendment 2] changes were 
removed) 
Now reads: 
Appendix 4, GBR 830-201 Protocol 
Amendment 2.0Summary of Changes 
in Current Protocol Amendment 
(contents reflecting protocol version 4 
[amendment 3] changes have been 
added) 
Previous appendix 4 that 
described changes in protocol 
version 3 (amendment 2) has 
been removed.  A new 
appendix 4 entitled “Summary 
of Changes in Current 
Protocol Amendment,” which 
describes changes in current 
protocol version 4 
(amendment 3), has been 
added.  
This change was done to 
remove an extra appendix that 
is no longer needed, avoid 
confusion at the site, and 
reduce the total number of 
pages in the protocol.