Conditions: Psoriasis
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 15
Healthy volunteers: no

Brief summary:
This is a single-arm, open-label study, which will examine the effect of secukinumab on the immunologic and genetic environment within psoriatic lesions.

Detailed description:
Quantitative analysis of the immunologic changes in immune cell populations will be performed after secukinumab treatment in 15 patients at weeks 2, 4, and 12 compared to baseline week 0. The immunologic profiles in psoriasis patients will also be compared to healthy control skin surgical discard specimens (n=10). The number of differentially expressed genes in each cell population will be quantified by RNA-seq at weeks 2, 4, 12 after secukinumab compared to baseline.

Arms:
arm 1: All subjects will receive Secukinumab 300mg SQ at weeks 0, 1, 2, 3, 4, and every 4 weeks thereafter until week 48.

Interventions: intervention 1: Secukinumab
Intervention descriptions: intervention 1: Secukinumab 300mg SQ at weeks 0, 1, 2, 3, 4, and every 4 weeks thereafter until week 48. Skin biopsy procedures will be performed at weeks 0, 2, 4, and 12.

Protocol document:
Prot_SAP_000.pdf: 
Clinical Research Protocol and Statistical 
Analysis Plan: Characterization of the 
response to secukinumab in plaque 
psoriasis using novel immunologic and 
genetic profiling 
 
 
NCT02592018 
 
Document Date: October 14, 2015 


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Clinical Research Protocol
Characterization of the response to secukinumab in plaque psoriasis using novel 
immunologic and genetic profiling
Protocol Number:
CAIN457AUS04T
Version Date:
October 14, 2015
Investigational Product:
Secukinumab
Sponsor/Principle 
Investigator:
Wilson Liao, MD
2340 Sutter St. Rm N426
San Francisco, CA 94115
Telephone: (415) 476-8364
Fax: (415) 476-8837
E-mail: wilson.liao@ucsf.edu
Funding Organization:
Novartis Pharmaceuticals
Approval:
PI or Sponsor Signature (Name and Title) 
Date
This confidential information about an investigational product is provided for the exclusive use of 
investigators of this product and is subject to recall at any time.  The information in this document 
may not be disclosed unless federal or state law or regulations require such disclosure.  Subject to the 
foregoing, this information may be disclosed only to those persons involved in the study who have a 
need to know, with the obligation not to further disseminate this information.  


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PROTOCOL AGREEMENT
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include ensuring the safety of the study subjects enrolled under my supervision and 
providing Novartis with complete and timely information, as outlined in the protocol.  It is 
understood that all information pertaining to the study will be held strictly confidential 
and that this confidentiality requirement applies to all study staff at this site. Furthermore, 
on behalf of the study staff and myself, I agree to maintain the procedures required to 
carry out the study in accordance with accepted GCP principles and to abide by the terms 
of this protocol.
Protocol Number:  CAIN457AUS04T
Protocol Title:  Characterization of the response to secukinumab in plaque psoriasis using 
novel immunologic and genetic profiling
Protocol Date:  August 10, 2015
Investigator Signature 
Date
Print Name and Title
Site #
Site Name
Address
Phone Number


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TABLE OF CONTENTS
1
BACKGROUND ...................................................................................................................9
2
STUDY RATIONALE..........................................................................................................9
2.1
Rationale for Flow Cytometry and RNA-Seq………………………………………....9
2.2
Risk / Benefit Assessment............................................................................................9
3
STUDY OBJECTIVES........................................................................................................12
3.1
Primary Objective ........................................................................................................12
3.2
Secondary Objectives...................................................................................................12
4
STUDY DESIGN..................................................................................................................12
4.1
Study Overview............................................................................................................12
5
CRITERIA FOR EVALUATION......................................................................................13
5.1
Primary Efficacy Endpoint...........................................................................................13
      5.2    Secondary Efficacy Endpoint……………………………………………………….....13
5.3
Safety Evaluations........................................................................................................13
6
SUBJECT SELECTION .....................................................................................................13
6.1
Study Population..........................................................................................................13
6.2
Inclusion Criteria..........................................................................................................13
6.3
Exclusion Criteria ........................................................................................................13
7
CONCURRENT MEDICATIONS.....................................................................................14
7.1
Allowed Medications and Treatments .........................................................................14
7.2    Prohibited Medications and Treatments.....………………...…………………………14
8
STUDY TREATMENTS.....................................................................................................15
8.1
Supply of Study Drug at the Site .................................................................................15
8.2
Storage .........................................................................................................................15
8.3
Dosage/Dosage Regimen……………………………………………………………...15
8.4
Administration instructions..........................................................................................15
       8.5    Study Drug Accountability…………………………………………………………....15
       8.6    Measures of Treatment Compliance..………………………………………………...15
9
STUDY PROCEDURES AND GUIDELINES..................................................................16
9.1
Clinical Assessments....................................................................................................16
9.2
Clinical Laboratory Measurements .............................................................................17
10 EVALUATIONS BY VISIT................................................................................................17
10.1 Visit 0 (Screening) .......................................................................................................17
10.2 Visit 1 (Week 0)...........................................................................................................18
10.3 Visit 2 (Week 1)...........................................................................................................18
10.4 Visit 3 (Week 2)...........................................................................................................18
10.5 Visit 4 (Week 3)...........................................................................................................18
10.6 Visit 5 (Week 4)...........................................................................................................18
10.7 Visit 6 (Week 8)...........................................................................................................18
10.8 Visit 7 (Week 12).........................................................................................................19


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10.9 Visit 8 (Week 16).........................................................................................................19
10.10 Visit 9 (Week 24).........................................................................................................19
10.11 Visit 10 (Week 36).......................................................................................................19
10.12 Visit 11 (Week 52).......................................................................................................19
10.13 Early Withdrawal Visit ................................................................................................20
11 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION ........................20
11.1 Adverse Events ............................................................................................................20
11.2 Serious Adverse Experiences (SAE)............................................................................22
11.3 Serious Adverse Experiences Reporting………………………………………….……22
12 DISCONTINUATION AND REPLACEMENT OF SUBJECTS ...................................23
12.1 Early Discontinuation of Study Drug……………………………………..…….….....23
12.2 Withdrawal of Subjects................................................................................................24
13 PROTOCOL VIOLATIONS………………………………………………………………24
14 STATISTICAL METHODS AND CONSIDERATIONS................................................24
13.1 Analysis of Primary Endpoint......................................................................................25
      13.3   Analysis of Secondary Endpoint……………………………………………………....25
      13.2
Sample Size..................................................................................................................25
15 DATA COLLECTION, RETENTION AND MONITORING........................................26
15.1 Data Collection Instruments.........................................................................................26
15.2 Data Management Procedures .....................................................................................26
15.3 Data Quality Control and Reporting ............................................................................27
15.4 Archival of Data...........................................................................................................27
15.5 Availability and Retention of Investigational Records ................................................27
15.6 Subject Confidentiality ................................................................................................27
16 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS...................27
16.1 Protocol Amendments..................................................................................................28
16.2 Institutional Review Boards and Independent Ethics Committees..............................28
16.3 Informed Consent Form...............................................................................................28
16.4 Publications..................................................................................................................29
16.5 Investigator Responsibilities........................................................................................29
17      References………………………………………………………………………………...30
List of Figures
    Fig 1. Multi-parameter flow cytometry of punch biopsies ………………………….….…....11
    Fig 2. RNA-sequencing studies at UCSF.……………………………………..……..………11
    Fig 3. Power to detect differentially expressed genes using RNA-Seq…………….…….…..26
List of Tables
     Table 1. AE Severity Grading……………………………………………………………..…20
     Table 2. AE Relationship to Study Drug……………...………………………………….…..20
Appendix
     Appendix 1. Evaluation Schedule ..........................................................................................32


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LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BUN
blood urea nitrogen
CBC
CFR
Complete blood count
Code of Federal Regulations
CRF
CXR
case report form
chest X-ray
DMC
Data Monitoring Committee
DSMB
Data Safety Monitoring Board
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
HIPAA
Health Insurance Portability and Accountability Act of 1996
ICF
informed consent form
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IL-17
Interleukin-17
IRB
IUD
Institutional Review Board
Intrauterine device
PASI
PGA
Psoriasis Area and Severity Index
Physician Global Assessment
PI
Principal Investigator
PK
QOL
RNA-seq
RT-PCR
Pharmacokinetic
Quality of life
RNA-sequencing
Reverse transcriptase polymerase chain reaction
SAE
serious adverse experience
SGOT
serum glutamic oxaloacetic transaminase
SGPT
SQ
Th-17
serum glutamate pyruvate transaminase
subcutaneously
T-helper 17


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PROTOCOL SYNOPSIS
TITLE
Characterization of the response to secukinumab in plaque psoriasis using 
novel immunologic and genetic profiling
SPONSOR
Wilson Liao, MD
FUNDING
Novartis Pharmaceuticals
STUDY DESIGN 
& OVERVIEW
This is a single-arm, open-label study, which will examine the effect of 
secukinumab on the immunologic and genetic environment within psoriatic 
lesions. 
PRIMARY 
OBJECTIVE
Perform quantitative analysis of the immunologic changes in immune cell 
populations after secukinumab treatment in 15 patients at weeks 2, 4, and 
12 compared to baseline week 0. The immunologic profiles in psoriasis 
patients will also be compared to healthy control skin surgical discard 
specimens (n=10). 
SECONDARY 
OBJECTIVES
Quantify the number of differentially expressed genes in each cell 
population by RNA-seq at weeks 2, 4, 12 after secukinumab compared to 
baseline.
NUMBER OF 
SUBJECTS
15
SUBJECT 
SELECTION
CRITERIA
Inclusion Criteria:
1. Ability to provide written informed consent and comply with the 
protocol. 
2. At least 18 years of age.
3. Diagnosis of predominately plaque psoriasis for at least 6 months prior 
to enrollment.
4. Subject is considered a candidate for phototherapy or systemic therapy
5. PASI ≥ 12
6. PGA ≥ 3
7. Subject has a negative Quantiferon Gold, or if positive undergoes 
CXR. If CXR negative, subject initiated prophylactic therapy with 
isoniazid for a course of 9 months with one month of therapy 
completed prior to first dose of secukinumab.
8. Subject does not have active or chronic hepatitis B or C. 
9. Subject does not have HIV (human immunodeficiency virus).
10. Subject is unlikely to conceive due to male, post-menopausal, or using 
adequate contraceptive (barrier, hormonal, implant, or permanent 
sterilization methods).
11. Physical exam within clinically acceptable limits.
Exclusion Criteria:
1. Subject is unable to provide written informed consent or comply with 
the protocol.
2. Subject is younger than 18 years of age.


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3. Subject has predominately non-plaque form of psoriasis.
4. Subject with mild psoriasis (PASI<12 and PGA<3) or is not a 
candidate for phototherapy or systemic treatments.
5. Subject has drug-induced psoriasis.
6. Subject with current, or a history of, severe psoriatic arthritis well 
controlled on current therapy.
7. Subjects with a serum creatinine level exceeding 176.8 μmol/L (2.0 
mg/dl).
8. Screening total white blood cell (WBC count) < 2,500/μl, platelets < 
100,000/μl, neutrophils < 1,500/μl, or hemoglobin <8.5 g/dl.
9. Evidence of active tuberculosis infection as defined by a positive 
QuantiFERON TB-Gold test (QFT) with a positive chest X-ray at 
screening, or untreated latent tuberculosis defined by positive QFT with 
a negative chest X-ray without prophylactic therapy with isoniazid for a 
course of 9 months with one month of therapy completed prior to first 
dose of secukinumab.
10. History of an active, ongoing, chronic or recurrent infectious disease 
including past medical history record of HIV, hepatitis B or hepatitis C.
11. Subjects possess other diagnoses that, in the investigator’s opinion, 
preclude him/her from safely participating in this study or interfere 
with the evaluation of the subject’s psoriasis.
12. History of known or suspected intolerance to any of the ingredients of 
the investigational study product.
13.  Pregnant or nursing (lactating) women, where pregnancy is defined as 
the state of a female after conception and until the termination of 
gestation, confirmed by a positive hCG laboratory test (>10 mIU/mL).
14. Women of child-bearing potential, defined as all women 
physiologically capable of becoming pregnant, unwilling to use 
effective contraception during the study and for 6 weeks after stopping 
treatment. 
STUDY 
TREATMENT
Secukinumab (Cosentyx™) 300mg SQ at weeks 0, 1, 2, 3, 4, and every 4 
weeks thereafter until week 48.
STUDY 
DURATION
The total duration of the study is expected to be 78 weeks: 26 weeks for 
recruitment and 52 weeks for site visits.
PRIMARY 
ENDPOINT
Percentage of CD4+ T effector cells expressing IL17 at weeks 2, 4, 12 
after secukinumab compared to baseline. 
SECNDARY 
ENDPOINT
Number of differentially expressed genes in each cell population by RNA-
seq at weeks 2, 4, 12 after secukinumab compared to baseline.
SAFETY 
EVALUATIONS
Safety and tolerability will be assessed by adverse events, vital signs, 
physical examinations (including   skin   examinations   and   injection-
site evaluations), and concomitant medication review. Laboratory 
assessments will be performed at screening. 


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STATISTICS
Primary Analysis 
Plan
Flow Cytometry: One sample paired t test comparing mean change in 
lesional IL-17A positive, CD4+ T lymphocytes compared to baseline.
RNA-seq: Identification of differentially expressed genes compared to 
baseline within each immune population studied using the statistical 
program EdgeR (paired analysis).
ETHICAL 
CONSIDER-
ATIONS
This study will be conducted in accordance with applicable laws and 
regulations and according to the recommendations of International 
Conference on Harmonization Good Clinical Practice (ICH GCP) 
guidelines and those of the Declaration of Helsinki (Edinburgh, 2000); 
only after approval for the study has been obtained from the relevant 
regulatory authority and relevant independent ethics committee (IEC). The 
institutional review board (IRB)/IEC must review and approve the protocol 
and informed consent form (ICF) before any subjects are enrolled. The 
subject must be consented using the approved ICF before any procedures 
specified in the protocol are performed.


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1
BACKGROUND
Secukinumab is the first FDA-approved therapy for moderate to severe plaque psoriasis in 
the class of recombinant high-affinity, fully human monoclonal antibody of the 
IgG1/kappa isotype that selectively targets Interleukin-17A (IL-17A). In the psoriatic 
skin, IL-17A is thought to be produced by infiltrating Th17 cells, neutrophils and mast 
cells. Upon activation of keratinocytes by IL-17A along with other synergistic 
inflammatory cytokines, further recruitment and activation of neutrophils, lymphocytes 
and myeloid cells eventually lead to a sustained local cutaneous inflammation that drives 
the psoriatic epidermal changes mediated by keratinocytes. This includes increase in 
epidermal thickness (acanthosis), increase in outer stratum corneum (hyperkeratosis) and 
retention of nuclei in the cornified layer (parakeratosis) (Martin 2013).
Secukinumab interferes in this pathologic process by selectively binding to IL-17A, 
thereby preventing IL-17A interaction with the IL-17 receptor expressed on keratinocytes. 
By its mechanism of action, secukinumab prevents and reverses key pathologic processes 
in psoriasis leading to normalization of skin histology.
Non-clinical studies have not shown any impediment to using secukinumab administered 
subcutaneously in man. 
The approval of secukinumab (Cosentyx™) is based on the safety and efficacy outcomes 
from 10 Phase II and Phase III studies, which included over 3,990 patients with moderate-
to-severe plaque psoriasis. This included the four pivotal Phase III trials – ERASURE, 
FIXTURE, FEATURE and JUNCTURE.
For more detail refer to the Prescribing Information.
2
STUDY RATIONALE
The University of California San Francisco Psoriasis Center has dual expertise in both 
immunologic and genetic analyses of psoriasis. Therefore, this unique proposal will 
examine the effect of secukinumab on the immunologic and genetic environment within 
psoriatic lesions.
2.1
Rationale for Flow Cytometry and RNA-Seq
Regarding understanding the impact of biologics on the molecular profile of psoriatic 
skin, a fundamental question that has not yet been adequately answered is: What is the 
response of specific cell populations in lesional skin to biologic treatment? A number of 
recent studies have used techniques such as RT-PCR, gene microarrays, and 
immunohistochemistry to evaluate changes in lesional skin in response to treatment with 
biologic agents (Zaba, Krueger, Hendriks, Johnston, Russell). These studies are limited by 
the use of bulk skin tissue, which does not permit precise quantitative analysis of 
individual cell types, and by the reliance on limited gene probe libraries used in RT-PCR 
or microarray analysis. Ideally, in order to understand the fundamental biology of how a 
biologic medication improves psoriasis, one would like to be able to isolate the different 
cell populations and study their individual characteristics.  Until now, this has not been 
possible.  


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At UCSF, we have developed innovative technologies to characterize individual skin cell 
populations at the protein and RNA level.  Using a novel flow cytometry protocol, we are 
able to separately analyze distinct skin populations such as CD4+ T cells, CD8+ T cells, 
regulatory T cells, and myeloid dendritic cells and measure the production of proteins 
such as IL-17, TNF-, IFN-, and IL-2 in parallel (Figure 1).  Because this technique is 
based on protein expression, it offers a truly functional view of the activity of cell 
populations in psoriasis, as methods using microarrays can measure only mRNA 
production, which does not necessarily accurately reflect protein expression (Villarino).
Moreover, we are able to perform RNA-sequencing on distinct cell populations. RNA-seq 
is a novel technique of quantifying gene expression in which RNA species are sequenced 
rather than hybridized as in microarrays. RNA-seq provides greater sensitivity than 
microarrays, particularly for low-expressed transcripts (Li et al). RNA-seq can also 
identify the expression of coding and noncoding transcripts that are absent on microarray 
platforms. Utilizing our innovative skin biopsy digestion protocol and cell sorting protocol 
described above, we are now able to perform RNA-seq on individual cell populations 
(Figure 2), permitting an understanding of the genetic and immunologic profile of 
individual cell types within psoriatic lesions.  Importantly, this cell type-level RNA-seq 
analysis has never previously been utilized to evaluate changes in patients undergoing 
biologic therapy.
Flow cytometry panel: Live/dead, CD45, CD3, CD4, CD8, Foxp3, IL-2, IL-17A, IL17-
F, TNF-, IFN-, IL-21, IL-22 and IL-23
RNA-seq cell types: CD4+ T effectors, CD4+ T Regs, CD8+ T effectors


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Figure 1. Multi-parameter flow cytometry of punch biopsies obtained from patients with psoriasis.  
We have recently developed and optimized a new flow cytometric-based protocol for comprehensively 
studying leukocyte populations isolated from human skin (Sanchez Rodriguez et al). Traditional approaches 
have relied on culturing skin biopsy specimens for 10-20 days in the presence of growth factors, to allow 
infiltrating leukocytes to expand in response to these factors. It is becoming increasingly appreciated that 
lymphocytes cultured for this length of time can alter their functional capabilities and may not accurately 
reflect in vivo differentiation and function. Using a single 4mm punch biopsy of freshly isolated human skin, 
we are now able to isolate lymphocytes and monocytes and immediately assess their functional activities in 
the absence of growth factors. We perform 15-color flow cytometry on these specimens, allowing for the 
quantification of multiple cytokine, chemokine, and cell surface and intracellular differentiation/activation 
markers at the protein level. Using this technique on 5mm skin punch biopsy specimens, we have analyzed 
the intracellular cytokine expression patterns from T cells infiltrating lesional and non-lesional skin of a 
patient with psoriasis (shown above). This data shows increased Tregs (denoted by Foxp3 expression) and 
increased TNF-, IL-17 and IFN- production from T cells infiltrating lesional psoriatic plaques when 
compared to non-lesional (normal appearing) skin from the same patient. All graphs are pre-gated on live 
CD3+CD4+ T cells. Numbers indicate percentage of cells per quadrant.
Figure 2. RNA-sequencing studies at UCSF. Whole transcriptome RNA-sequencing of CD4+ Tregs and 
Teffs isolated from normal human skin. Tregs and Teffs were sorted from normal skin using expression of 
CD25 and CD27. RNA was isolated from these purified cell fractions and subjected to whole transcriptome 
RNA-sequencing. Scatter plot shows grouped Treg vs. Teff comparisons.


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2.2
Risk / Benefit Assessment
Details of the risk and benefits of secukinumab are outlined in the Prescribing 
Information. Side effects of secukinumab include nasopharyngitis (11.4%), diarrhea 
(4.1%), and upper respiratory infections (2.5%). Serious side effects include anaphylaxis 
and exacerbation of Crohn’s disease. The risk to subjects in this trial will be minimized by 
compliance with the inclusion/exclusion criteria, proper study design, and close clinical 
monitoring.
In regards to skin biopsy procedures, as in any surgical procedure, there are certain 
inherent risks including bleeding, post-operative pain, infection, reactions to sutures, 
anesthetics or topical antibiotics, and scarring. All reasonable efforts will be made to 
minimize the possibility of these potential complications.
The benefit to subjects is that they will be receiving an approved therapy for moderate-to-
severe psoriasis. Although it cannot be guaranteed, secukinumab has shown to be safe and 
effective in moderate-to-severe psoriasis. An additional benefit to patients is that they are 
contributing to society by helping the enhancement of science. 
3
STUDY OBJECTIVES
3.1
Primary Objective
Perform quantitative analysis of the immunologic and genetic changes in immune cell 
populations after secukinumab treatment in 15 patients at weeks 2, 4, 12 compared to 
baseline week 0. The immunologic profiles in psoriasis patients will also be compared to 
healthy control skin surgical discard specimens (n=10). 
3.2
Secondary Objectives
Quantify the number of differentially expressed genes in each cell population by RNA-seq 
at weeks 2, 4, 12 after secukinumab compared to baseline.
4
STUDY DESIGN
4.1
Study Overview
This is a single center, open-label study. 15 subjects are planned. Screening data will be 
reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and 
none of the exclusion criteria will be entered into the study. Each subject will be 
administered FDA approved dose of secukinumab 300mg subcutaneously at weeks 0, 1, 2, 
3, 4, then every 4 weeks thereafter until week 48. All 15 patients will undergo skin 
biopsies at weeks 0, 2, 4, and 12 for molecular profiling. Total duration of subject 
participation will be 52 weeks.  Total duration of the study is expected to be 78 weeks, 
which includes 26 weeks of recruitment.


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5
CRITERIA FOR EVALUATION
5.1
Primary Analysis Endpoint
Percentage of CD4+ T effector cells expressing IL17 at weeks 2, 4, 12 after secukinumab 
compared to baseline. 
5.2
Secondary Analysis Endpoint
Number of differentially expressed genes in each cell population by RNA-seq at weeks 2, 
4, 12 after secukinumab compared to baseline.
5.3
Safety Evaluations
Safety and tolerability to secukinumab will be assessed by adverse events, vital signs, 
physical examinations (including skin examinations and injection-site evaluations), and 
concomitant medication review. Laboratory assessments will be performed at screening.
6
SUBJECT SELECTION
6.1
Study Population
Subjects with a diagnosis of predominately plaque psoriasis for at least 6 months prior to 
enrollment who meet the inclusion and exclusion criteria will be eligible for participation 
in this study.  
6.2
Inclusion Criteria
1. Ability to provide written informed consent and comply with the protocol. 
2. At least 18 years of age.
3. Diagnosis of predominately plaque psoriasis for at least 6 months prior to enrollment.
4. Subject is considered a candidate for phototherapy or systemic therapy
5. PASI ≥ 12
6. PGA ≥ 3
7. Subject has a negative Quantiferon Gold, or if positive undergoes CXR. If CXR 
negative, subject initiated prophylactic therapy with isoniazid for a course of 9 months 
with one month of therapy completed prior to first dose of secukinumab.
8. Subject does not have active or chronic hepatitis B or C. 
9. Subject does not have HIV (human immunodeficiency virus).
10. Subject is unlikely to conceive due to male, post-menopausal, or using adequate 
contraceptive (barrier, hormonal, implant, or permanent sterilization methods).
11. Physical exam within clinically acceptable limits.
6.3 Exclusion Criteria
1. Subject is unable to provide written informed consent or comply with the protocol.
2. Subject is younger than 18 years of age.
3. Subject has predominately non-plaque form of psoriasis.
4. Subject with mild psoriasis (PASI<12 and PGA<3) or is not a candidate for 
phototherapy or systemic treatments.


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5. Subject has drug-induced psoriasis.
6. Subject with current, or a history of, severe psoriatic arthritis well controlled on 
current therapy.
7. Subjects with a serum creatinine level exceeding 176.8 μmol/L (2.0 mg/dl).
8. Screening total white blood cell (WBC count) < 2,500/μl, platelets < 100,000/μl, 
neutrophils < 1,500/μl, or hemoglobin <8.5 g/dl.
9. Evidence of active tuberculosis infection as defined by a positive QuantiFERON TB-
Gold test (QFT) with a positive chest X-ray at screening, or untreated latent 
tuberculosis defined by positive QFT with a negative chest X-ray without prophylactic 
therapy with isoniazid for a course of 9 months with one month of therapy completed 
prior to first dose of secukinumab.
10. History of an ongoing, chronic or recurrent infectious disease including past medical 
history record of HIV, hepatitis B or hepatitis C.
11. Subjects possess other diagnoses that, in the investigator’s opinion, preclude him/her 
from safely participating in this study or interfere with the evaluation of the subject’s 
psoriasis.
12. History of known or suspected intolerance to any of the ingredients of the 
investigational study product.
13. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a 
female after conception and until the termination of gestation, confirmed by a positive 
hCG laboratory test (>10 mIU/mL).
14. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unwilling to use effective contraception during the study and for 6 
weeks after stopping treatment. Effective contraception is defined as either:
Barrier method: Condom or occlusive cap (diaphragm or cervical/vault caps) with 
spermicide (where available). Spermicides alone are not a barrier method of contraception 
and should not be used alone.
The following methods are considered more effective than the barrier method and are also 
acceptable:

Total abstinence: When this is in line with the preferred and usual lifestyle of the 
subject (Periodic abstinence [e.g. calendar, ovulation, symptothermal, post-
ovulation methods] and withdrawal are not acceptable methods of contraception)

Female sterilization: have had a surgical bilateral oophorectomy (with or without 
hysterectomy) or tubal ligation at least six weeks before taking study treatment. In 
case of oophorectomy alone, only when the reproductive status of the woman has 
been confirmed by follow up hormone level assessment.

Male partner sterilization (at least 6 months prior to screening). For female 
subjects on the study, the vasectomised male partner should be the sole partner for 
that subject.

Use of established oral, injected or implanted hormonal methods of contraception, 
intrauterine device (IUD) or intrauterine system (IUS)


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NOTE: Women are considered post-menopausal and not of child bearing potential if 
they have had: 12 months of natural (spontaneous) amenorrhea with an appropriate 
clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of 
spontaneous amenorrhea with serum FSH levels >40 mIU/mL and estradiol <20 
pg/mL or surgical bilateral oophorectomy (with or without hysterectomy) or tubal 
ligation at least six weeks before taking study treatment. In case of oophorectomy 
alone - only when the reproductive status of the woman has been confirmed.
7
CONCURRENT MEDICATIONS
7.1
Allowed Medications and Treatments
All prior concomitant medications must be on a stable dose for at least 4 weeks before the 
first study treatment administration. All subjects should be maintained on the same 
medications throughout the entire study period, as medically feasible. Any changes in 
medications and medication dosing will be recorded on the CRF. After the screening 
period, the use of concomitant medication for psoriasis in all body regions is restricted to 
bland emollients and other non-medicated interventions.
7.2
Prohibited Medications and Treatments
The following are prohibited during the study and prior to the study for a set duration as 
follows: 

Systemic anti-psoriatic treatments including methotrexate, cyclosporine, 
corticosteroids, and cyclophosphamide: 4 weeks.

Biological immunomodulating agents including infliximab, etanercept, and 
adalimumab: 12 weeks

Ustekinumab: 6 months 

Other systemic psoriasis treatments including retinoids: 4 weeks

Photochemotherapy: 4 weeks

Phototherapy (UVA/UVB):  2 weeks

Topical treatment that is likely to impact signs and symptoms of psoriasis such as 
corticosteroids, vitamin D analogues, pimecrolimus, retinoids, salicylic acid, lactic 
acid, tacrolimus, tar, urea, α-hydroxy or fruit acids: 2 weeks

 Live vaccinations: 6 weeks

Any investigational treatment or participation in any interventional trial: 4 weeks or 
5 half-lives, whichever is longer 
8
STUDY TREATMENTS  
Secukinumab (Cosentyx™) 
8.1
Supply of Study Drug at the Site
Novartis will ship the study drug to the investigational sites. The study drug is supplied in 
a carton of one 150 mg/mL (300 mg dose) Sensoready pens. Each kit of study drug will be 
labeled with the required FDA warning statement, the protocol number, and directions for 
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8.2
Storage
Secukinumab Sensoready pens must be refrigerated at 2ºC to 8ºC (36ºF to 46ºF). The 
medication will be kept in a temperature-monitored refrigerator at the study site. The 
product will be kept in the original carton until the time of use.
8.3
Dosage/Dosage Regimen
Secukinumab will be administered at a dose of 300mg subcutaneously through the study, 
which a FDA-approved and recommended dose for secukinumab. There is no weight-
based dosing. The dosing schedule will be as follows: secukinumab 300mg 
subqutaneously once a week at weeks 0, 1, 2, 3, and 4, then every four weeks thereafter 
until week 48. 
8.4
Administration Instructions 
All doses of study treatment will be administered at the study site after the study 
assessments for the visit have been completed at visits occurring between week 1 and 16. 
After week 16 subjects will administer the medication independently every 4 weeks only 
after they have shown the competency to self-administer the treatment outside of the study 
site. There will be no medication given after week 48. 
The subject should be instructed to contact the investigator if he/she is unable for any 
reason to attend a study visit as scheduled. All dates and times of injections done to the 
subject during the study must be recorded on the Dosage Administration Record CRF. 
The investigator will promote compliance by instructing the subject to attend the study 
visits as scheduled and by stating that compliance is necessary for the subject’s safety and 
the validity of the study.
8.5
Study Drug Accountability
The qualified site personnel will maintain an accurate record of the shipment and 
dispensing of study treatment in a treatment accountability log. All study treatment kits 
assigned to the subject during the study will be recorded. 
8.6
Measures of Treatment Compliance
Subjects will be given scheduled doses of secukinumab at each visit from visit 0 (week 1) 
until visit 8 (week 16). After week 16, subjects will be given a dosing diary to record their 
scheduled injections administered at home every 4 weeks.
9
STUDY PROCEDURES AND GUIDELINES
A Schedule of Events representing the required testing procedures to be performed for the 
duration of the study is diagrammed in Appendix 1.
Prior to conducting any study-related activities, written informed consent and the Health 
Insurance Portability and Accountability Act (HIPAA) authorization must be signed and 
dated by the subject.
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CCA 94118
All blood draws will take place at Health Exams, Inc laboratory: 3580 California St., San 
Francisco, CA 94118.
9.1
Clinical Assessments
9.1.1
Medical History 
Relevant medical history, including history of current disease, and information regarding 
underlying diseases will be recorded at Screening.
11.1.2
Concomitant Medications
All concomitant medication and concurrent therapies will be documented at Screening, at 
every site visit, and at early termination when applicable.  Dose, route, unit frequency of 
administration, and indication for administration and dates of medication will be captured.
9.1.3
Demographics 
Demographic information (date of birth, gender, race) will be recorded at Screening.
9.1.4
Physical Examination
A complete physical examination will be performed by either the investigator or a sub-
investigator who is a physician at screening and weeks 0, 12, 24, and 52. New abnormal 
physical exam findings must be documented and will be followed by a physician or other 
qualified staff at the next scheduled visit.
9.1.5
Vital Signs
Body temperature, blood pressure, pulse and respirations will be performed after resting 
for 5 minutes at all site visits. 
9.1.6
Adverse Events
Information regarding occurrence of adverse events will be captured throughout the study. 
Duration (start and stop dates and times), severity/grade, outcome, treatment and relation 
to study drug will be recorded on the case report form (CRF).
9.1.7
PASI and PGA
Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA) will 
be completed at screening and weeks 0, 4, 8, 12, 24, 36, and 52.
9.1.8
Photography
Photographs (full front and back) will be taken at weeks 0, 2, 4, 12, and 52. 
9.2 Clinical Laboratory Measurements
9.2.1
Hematology
Blood will be obtained and sent to the clinical hematology lab for a complete blood count 
(hemoglobin, hematocrit, red blood cell count, white blood cell count, white blood cell 


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differential, and platelet count) determinations for assessment of systemic evidence for 
infection and/or inflammation at Screening.
9.2.2
Blood Chemistry Profile
Blood will be obtained and sent to the clinical chemistry lab for determination of 
electrolyte levels, serum BUN, creatinine, AST, ALT, and alkaline phosphatase at 
screening.
9.2.3
Pregnancy Test
A urine pregnancy test will be obtained at the study site for female subjects of 
childbearing age at screening and weeks 0, 4, 8, 12, 16, 24, 36, and 52.
9.2.4
Hepatitis B/C and HIV Testing
Blood will be obtained and sent to the clinical lab for determination of hepatitis B and C 
and HIV status at Screening.
9.2.5
Quantiferon Gold with or without chest X-ray
Blood will be obtained and sent to the clinical lab for determination of tuberculosis 
infection at Screening. If positive, a chest X-ray will be obtained to assess for active vs. 
latent tuberculosis status.
10
EVALUATIONS BY VISIT
See Appendix 1. 
1.1
Visit 0 (Screening)
1.
Review inclusion/exclusion criteria.
2.
Review the study with the subject and obtain written informed consent and 
HIPAA authorization and assent, if appropriate.
3.
Assign the subject a unique screening number.
4.
Record demographics data.
5.
Record medical history, including a history of plaque psoriasis, diagnosis date, 
and prior treatments for psoriasis.
6.
Record concomitant medications.
7.
Perform a complete physical examination.
8.
Perform PASI and PGA.
9.
Perform and record vital signs.
10. Collect blood for clinical laboratory tests (CBC, serum electrolytes, BUN, 
Creatinine, AST, ALT, alkaline phosphatase, Hepatitis B/C, HIV, Quantiferon 
Gold with/without CXR).
11. Perform urine pregnancy test (if applicable).
1.2
Visit 1 (Week 0)
1. Record any Adverse Experiences.
2. Concomitant medications review.
3. Perform a complete physical examination.
4. Perform and record vital signs.


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5. Perform PASI and PGA.
6. Perform urine pregnancy test (if applicable)
7. Perform skin biopsy procedure.
8. Obtain photographs.
9. Dispense study medication.
1.3
Visit 2 (week 1)
1. Record any Adverse Experiences.
2. Concomitant medications review.
3. Perform and record vital signs.
4. Dispense study medication.
10.4
Visit 3 (week 2) 
1. Record any Adverse Experiences
2. Concomitant medications review.
3. Perform and record vital signs.
4. Perform skin biopsy procedure.
5. Obtain photographs.
6. Dispense medication.
10.5
Visit 4 (week 3) 
1. Record any Adverse Experiences.
2. Concomitant medication review.
3. Perform and record vital signs.
4. Dispense study medication.
10.6
Visit 5 (week 4)
1. Record any Adverse Experiences.
2. Concomitant medications review.
3. Perform and record vital signs.
4. Perform PASI and PGA.
5. Perform urine pregnancy test (if applicable)
6. Perform skin biopsy procedure.
7. Obtain photographs.
8. Dispense study medication.
10.7
Visit 6 (week 8)
1. Record any Adverse Experiences.
2. Concomitant medications review.
3. Perform and record vital signs.
4. Perform PASI and PGA assessments.
5. Perform urine pregnancy test (if applicable).
6. Dispense study medication.
10.8
Visit 7 (week 12)
1. Record any Adverse Experiences.
2. Concomitant medications review.


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3. Perform complete physical exam.
4. Perform and record vital signs.
5. Perform PASI and PGA.
6. Perform urine pregnancy test (if applicable)
7. Perform skin biopsy.
8. Obtain photographs.
9. Dispense study medication
10.9
Visit 8 (week 16)
1. Record any Adverse Experiences.
2. Concomitant medications review.
3. Perform and record vital signs.
4. Perform PASI and PGA.
5. Perform urine pregnancy test (if applicable)
6. Dispense study medication
10.10 Visit 9 (week 24)
1. Record any Adverse Experiences.
2. Concomitant medications review.
3. Perform complete physical examination.
4. Perform and record vital signs.
5. Perform PASI and PGA.
6. Perform urine pregnancy test (if applicable).
7. Dispense study medication.
10.11 Visit 10 (week 36)
1. Record any Adverse Experiences.
2. Concomitant medications review.
3. Perform and record vital signs.
4. Perform PASI and PGA.
5. Perform urine pregnancy test (if applicable).
6. Dispense study medication.
10.12 Visit 11: END OF STUDY (week 52)
1. Record any Adverse Experiences.
2. Concomitant medications review.
3. Perform complete physical examination.
4. Perform and record vital signs.
5. Perform PASI and PGA.
6. Perform urine pregnancy test (if applicable).
7. Obtain photographs.
10.13 EARLY TERMINATION
1. Record any Adverse Experiences.
2. Concomitant medications review.
3. Perform complete physical examination.


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4. Perform and record vital signs.
5. Perform PASI and PGA.
6. Perform urine pregnancy test (if applicable).
7. Obtain photographs.
11 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION
11.1
Adverse Events
Definition of an AE: Any untoward medical occurrence in a subject administered a 
pharmaceutical product that does not necessarily have a causal relationship with the 
treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not considered related to the 
investigational medicinal product.
Investigational Medicinal Product (IMP) includes the drug under evaluation and the 
comparator drug(s) if specified as part of the research objective, given at any time during 
the study. Medical conditions/diseases present before starting the drug of interest are only 
considered adverse events if they worsen after starting the drug of interest.
The occurrence of adverse events will be sought by non-directive questioning of the 
patient at each visit during the study. Adverse events also may be detected when they are 
volunteered by the patient during or between visits or through physical examination, 
laboratory test, or other assessments. All adverse events will be recorded in the study 
database including the following information:
1. the severity grade (mild, moderate, severe)
2. its relationship to the drug(s) of interest (suspected/not suspected)
3. its duration (start and end dates or if continuing at final exam)
4. whether it constitutes a serious adverse event (SAE)
AE Severity
The National Cancer Institute’s Common Terminology Criteria for Adverse Events 
(CTCAE) Version 3.0 should be used to assess and grade AE severity, including 
laboratory abnormalities judged to be clinically significant. The modified criteria can be 
found in the study manual.  If the experience is not covered in the modified criteria, the 
guidelines shown in Error! Reference source not found. below should be used to grade 
severity.  It should be pointed out that the term “severe” is a measure of intensity and that 
a severe AE is not necessarily serious.


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Table 1.  AE Severity Grading
Severity (Toxicity Grade)
Description
Mild (1)
Transient or mild discomfort; no limitation in activity; no medical 
intervention or therapy required. The subject may be aware of the sign 
or symptom but tolerates it reasonably well.
Moderate (2)
Mild to moderate limitation in activity, no or minimal medical 
intervention/therapy required.
Severe (3)
Marked limitation in activity, medical intervention/therapy required, 
hospitalizations possible.
Life-threatening (4)
The subject is at risk of death due to the adverse experience as it 
occurred. This does not refer to an experience that hypothetically 
might have caused death if it were more severe.
Table 2.  AE Relationship to Study Drug
Relationship
to Drug
Comment
Definitely
Previously known toxicity of agent; or an event that follows a reasonable temporal 
sequence from administration of the drug; that follows a known or expected response 
pattern to the suspected drug; that is confirmed by stopping or reducing the dosage of 
the drug; and that is not explained by any other reasonable hypothesis.
Probably
An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to the suspected drug; that is 
confirmed by stopping or reducing the dosage of the drug; and that is unlikely to be 
explained by the known characteristics of the subject’s clinical state or by other 
interventions.
Possibly
An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to that suspected drug; but 
that could readily have been produced by a number of other factors.
Unrelated
An event that can be determined with certainty to have no relationship to the study 
drug.


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11.2
Serious Adverse Experiences (SAE)
A SAE is any untoward medical occurrence that at any dose:

results in death,

is life-threatening,

requires inpatient hospitalization or prolongation of existing hospitalization,

results in persistent or significant disability/incapacity,

is a congenital anomaly/birth defect, 

is otherwise a significant medical event.
This includes any SAEs likely to arise from the trial indication or progression of 
underlying/concomitant illness(es) (e.g. progression of cancer in oncology trials), unless 
specified in the protocol as study specific exemptions.
Any SAE, irrespective of causality, occurring after the subject has provided informed 
consent and until four weeks after the subject has stopped study participation must be 
reported unless otherwise stated in the protocol. SAEs occurring after four weeks from 
ending study participation should only be reported if considered by the Investigator 
attributable to the exposure to the investigational drug(s) during the trial period. This 
includes the period in which the study protocol interferes with the standard medical 
treatment given to a subject, even if study treatment has not yet started (e.g. withdrawal of 
previous treatment during washout period, change in treatment to a fixed dose of 
concomitant medication).
11.3
Serious Adverse Experience Reporting
Study sites will document all SAEs that occur (whether or not related to study drug) per 
UCSF CHR Guidelines.  The collection period for all SAEs will begin after informed 
consent is obtained and end after procedures for the final study visit have been completed.
SAEs occurring after four weeks from ending study participation should only be reported 
if considered by the Investigator attributable to the exposure to the investigational drug(s) 
during the trial period. This includes the period in which the study protocol interferes with 
the standard medical treatment given to a subject, even if study treatment has not yet 
started (e.g. withdrawal of previous treatment during washout period, change in treatment 
to a fixed dose of concomitant medication).
In accordance with the standard operating procedures and policies of the local Institutional 
Review Board (IRB)/Independent Ethics Committee (IEC), the site investigator will report 
SAEs to the IRB/IEC.  
Timelines: All serious adverse events (SAEs) must be reported by the sites to Sponsor 
within 24 hours of occurrence of the SAE. The timelines for investigator initiated trials 
reporting to Novartis will be done as per Third Party Study/Investigator Initiated Trial 
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Follow-up reports: SAEs will be followed until resolution or until it is judged to be 
permanent, and an assessment will be made at each visit (or more frequently, if necessary) 
of any changes in severity, the suspected relationship to the drug of interest, the 
interventions required to treat it, and the outcome. 
The Sponsor shall support Novartis in the following-up of all SAEs so that complete 
information is available to maintain patient safety and also as part of any commitments by 
Novartis to any Health authority OR specific Health authority follow-up requests for the 
product under investigation.
Pregnancies: Any occurrences of a pregnancy in a patient (or a patients partner) during 
study participation will be collected. All pregnancies will be followed up to determine 
outcome, including spontaneous or voluntary termination, details of the birth, and the 
presence or absence of any birth defects, congenital abnormalities, or maternal and/or 
newborn complications.
12
DISCONTINUATION AND REPLACEMENT OF SUBJECTS
12.1 Early Discontinuation of Study Drug 
A subject may be discontinued from study treatment at any time if the subject, the 
investigator, or the Sponsor feels that it is not in the subject’s best interest to continue.  
The following is a list of possible reasons for study treatment discontinuation: 

Subject withdrawal of consent (or assent)

Subject is not compliant with study procedures

Adverse event that in the opinion of the investigator would be in the best interest 
of the subject to discontinue study treatment

Protocol violation requiring discontinuation of study treatment

Lost to follow-up

Sponsor request for early termination of study

Positive pregnancy test (females)
If a subject is withdrawn from treatment due to an adverse event, the subject will be 
followed and treated by the Investigator until the abnormal parameter or symptom has 
resolved or stabilized.  
All subjects who discontinue study treatment should come in for an early discontinuation 
visit as soon as possible and then should be encouraged to complete all remaining 
scheduled visits and procedures.
All subjects are free to withdraw from participation at any time, for any reason, specified 
or unspecified, and without prejudice.
Reasonable attempts will be made by the investigator to provide a reason for subject 
withdrawals.  The reason for the subject’s withdrawal from the study will be specified in 
the subject’s source documents Refer to Section 10.13 for early termination procedures.


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12.2
Withdrawal of Subjects from the Study
A subject may be withdrawn from the study at any time if the subject, the investigator, or 
the Sponsor feels that it is not in the subject’s best interest to continue.  
All subjects are free to withdraw from participation at any time, for any reason, specified 
or unspecified, and without prejudice.
Reasonable attempts will be made by the investigator to provide a reason for subject 
withdrawals.  The reason for the subject’s withdrawal from the study will be specified in 
the subject’s source documents. As noted above, subjects who discontinue study treatment 
early (i.e., they withdraw prior to Visit 11) should have an early discontinuation visit. 
Refer to Section 10.13 for early termination procedures. Subjects who withdraw after 
Visit 1 but prior to Visit 52 should be encouraged to come in for a final visit (and the 
procedures to be followed would include those for their next scheduled visit). Subjects 
who sign the informed consent form (ICF) and who are discontinued or withdraw from the 
study before study product administration will be defined as screen failures. No data will 
be collected in the CRFs for screen failure subjects.
13
PROTOCOL VIOLATIONS
A protocol violation occurs when the subject, investigator, or Sponsor fails to adhere to 
significant protocol requirements affecting the inclusion, exclusion, subject safety and 
primary endpoint criteria.  Protocol violations for this study include, but are not limited to, 
the following:

Failure to meet inclusion/exclusion criteria.

Use of a prohibited concomitant medication.

Non-compliance with study drug regimen.

Non-compliance with study visit procedures.

Failure to comply with Good Clinical Practice (GCP) guidelines will also result in 
a protocol violation. The PI will determine if a protocol violation will result in 
withdrawal of a subject.
When a protocol violation occurs, it will be discussed with the investigator and a Protocol 
Violation Form detailing the violation will be generated. This form will be signed by a 
Sponsor representative and the Investigator. A copy of the form will be filed in the site’s 
regulatory binder and in the Sponsor’s files.
14 STATISTICAL METHODS AND CONSIDERATIONS
Prior to the analysis of the final study data, a detailed Statistical Analysis Plan (SAP) will 
be written describing all analyses that will be performed.  The SAP will contain any 
modifications to the analysis plan described below.  
14.1 Analysis of Primary Endpoint
Flow Cytometry: One sample paired t-test comparing mean change in lesional IL-17A 
positive, CD4+ T lymphocytes at weeks 2, 4, 12 compared to baseline.


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14.2
Analysis Secondary Endpoint
RNA-seq: Identification of differentially expressed genes at weeks 2, 4, 12 compared to 
baseline within each immune population studied using the statistical program EdgeR 
(paired analysis).
14.3  Safety Data
Safety and tolerability data will be summarized by treatment group. 
Adverse event rates will be coded by body system and MedDra classification term. 
 Adverse events will be tabulated by treatment group and will include the number of 
patients for whom the event occurred, the rate of occurrence, and the severity and 
relationship to study drug.  
14.4 Sample Size
15 subjects will receive secukinumab for a treatment period of 52 weeks (i.e. last injection 
on week 48). All subjects will undergo skin biopsies for molecular profiling.
Sample size justification
Flow cytometry: Since these measurements using real-time flow cytometry have never 
been previously reported, we will have to estimate the minimum effect size that would be 
clinically relevant. Given the results of pilot testing of our methods using ustekinumab in 
plaque psoriasis, we believe a reduction in lesional IL-17A positive, CD4+ T lymphocytes 
of 10% is clinically meaningful (i.e., results in clinical improvement). The standard 
deviation of the change in lesional IL-17A positive, CD4+ T-lymphocytes in the patient 
population is estimated at 10% (also extrapolated from data generated with ustekinumab). 
Therefore, our standardized effect size is 1.00. For the statistical analysis, we will set 
alpha at 0.05, beta at 0.20 (power = 0.8). The resulting sample size estimate for a one 
sample paired.
RNA-seq: To determine statistical power to identify differentially expressed genes as 
measured by RNA-seq, we used the Scotty (Busby et al.) power calculator which uses a t-
statistic and incorporates the variance attributable to read depth. Performing RNA-seq on 
15 samples before and after treatment to a read depth of 50 million per sample as 
proposed here, we can detect >97% of transcripts displaying 2X fold change and >80% of 
transcripts displaying 1.5X fold change with p<0.01 (Figure 3).


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Fig 3. Power to detect differentially 
expressed genes using RNA-Seq.
15 DATA COLLECTION, RETENTION AND MONITORING
15.1
Data Collection Instruments
The Investigator will prepare and maintain adequate and accurate source documents 
designed to record all observations and other pertinent data for each subject. Study 
personnel at each site will enter data from source documents corresponding to a subject’s 
visit into the protocol-specific electronic or paper Case Report Form (eCRF) when the 
information corresponding to that visit is available. Subjects will not be identified by 
name in the study database or on any study documents, but will be identified by a site 
number, subject number and initials.
If a correction is required for an eCRF, the time and date stamps track the person entering 
or updating eCRF data and creates an electronic audit trail. If a correction is made on a 
paper CRF, the study staff member will line through the incorrect data, write in the correct 
data and initial and date the change.
The Investigator is responsible for all information collected on subjects enrolled in this 
study.  All data collected during the course of this study must be reviewed and verified for 
completeness and accuracy by the Investigator. A copy of the CRF will remain at the 
Investigator’s site at the completion of the study.
15.2
Data Management Procedures
The data will be entered into a validated database.  The Data Management group will be 
responsible for data processing, in accordance with procedural documentation.  Database 
lock will occur once quality assurance procedures have been completed.
All procedures for the handling and analysis of data will be conducted using good 
computing practices meeting FDA guidelines for the handling and analysis of data for 
clinical trials.


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15.3
Data Quality Control and Reporting
After data have been entered into the study database, a system of computerized data 
validation checks will be implemented and applied to the database on a regular basis. On 
eCRFs, queries are entered, tracked, and resolved through the EDC system directly. On 
paper, query reports (Data Clarification Requests) pertaining to data omissions and 
discrepancies will be forwarded to the Investigators and study monitors for resolution.  
The study database will be updated in accordance with the resolved queries.  All changes 
to the study database will be documented.
15.4
Archival of Data
The database is safeguarded against unauthorized access by established security 
procedures; appropriate backup copies of the database and related software files will be 
maintained.  Databases are backed up by the database administrator in conjunction with 
any updates or changes to the database.  
At critical junctures of the protocol (e.g., production of interim reports and final reports), 
data for analysis is locked and cleaned per established procedures.
15.5
Availability and Retention of Investigational Records
The Investigator must make study data accessible to the monitor, other authorized 
representatives of the Sponsor (or designee), IRB/IEC, and Regulatory Agency (e.g., 
FDA) inspectors upon request.  A file for each subject must be maintained that includes 
the signed Informed Consent, HIPAA Authorization and Assent Form and copies of all 
source documentation related to that subject.  The Investigator must ensure the reliability 
and availability of source documents from which the information on the CRF was derived.
All study documents (patient files, signed informed consent forms, copies of CRFs, Study 
File Notebook, etc.) must be kept secured for a period of two years following marketing of 
the investigational product or for two years after centers have been notified that the IND 
has been discontinued. There may be other circumstances for which the Sponsor is 
required to maintain study records and, therefore, the Sponsor should be contacted prior to 
removing study records for any reason.
15.6
Subject Confidentiality
In order to maintain subject confidentiality, only a site number, subject number and 
subject initials will identify all study subjects on CRFs and other documentation submitted 
to the Sponsor.  Additional subject confidentiality issues (if applicable) are covered in the 
Clinical Study Agreement.
16 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS
The study will be conducted according to the Declaration of Helsinki, Protection of 
Human Volunteers (21 CFR 50), Institutional Review Boards (21 CFR 56), and 
Obligations of Clinical Investigators (21 CFR 312).
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other 
records will be identified by a coded number and initials only. All study records will be 
kept in a locked file cabinet and code sheets linking a patient’s name to a patient 


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identification number will be stored separately in another locked file cabinet.  Clinical 
information will not be released without written permission of the subject, except as 
necessary for monitoring by the FDA.  The Investigator must also comply with all 
applicable privacy regulations (e.g., Health Insurance Portability and Accountability Act 
of 1996, EU Data Protection Directive 95/46/EC).
16.1
Protocol Amendments
Any amendment to the protocol will be written by the PI or a sub-investigator with the 
PI’s approval. Protocol amendments cannot be implemented without prior written 
IRB/IEC approval except as necessary to eliminate immediate safety hazards to patients.  
A protocol amendment intended to eliminate an apparent immediate hazard to patients 
may be implemented immediately, provided the IRBs are notified within five working 
days.
16.2
Institutional Review Boards and Independent Ethics Committees
The protocol and consent form will be reviewed and approved by the IRB/IEC of each 
participating center prior to study initiation.  Serious adverse experiences regardless of 
causality will be reported to the IRB/IEC in accordance with the standard operating 
procedures and policies of the IRB/IEC, and the Investigator will keep the IRB/IEC 
informed as to the progress of the study.  The Investigator will obtain assurance of 
IRB/IEC compliance with regulations.
Any documents that the IRB/IEC may need to fulfill its responsibilities (such as protocol, 
protocol amendments, Investigator’s Brochure, consent forms, information concerning 
patient recruitment, payment or compensation procedures, or other pertinent information) 
will be submitted to the IRB/IEC.  The IRB/IECs written unconditional approval of the 
study protocol and the informed consent form will be in the possession of the Investigator 
before the study is initiated.  The IRB/IECs unconditional approval statement will be 
transmitted by the Investigator to the designee prior to the shipment of study supplies to 
the site.  This approval must refer to the study by exact protocol title and number and 
should identify the documents reviewed and the date of review.
Protocol and/or informed consent modifications or changes may not be initiated without 
prior written IRB/IEC approval except when necessary to eliminate immediate hazards to 
the patients or when the change(s) involves only logistical or administrative aspects of the 
study.  Such modifications will be submitted to the IRB/IEC and written verification that 
the modification was submitted and subsequently approved should be obtained.  
The IRB/IEC must be informed of revisions to other documents originally submitted for 
review; serious and/or unexpected adverse experiences occurring during the study in 
accordance with the standard operating procedures and policies of the IRB; new 
information that may affect adversely the safety of the patients of the conduct of the study; 
an annual update and/or request for re-approval; and when the study has been completed.
16.3
Informed Consent Form 
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH 
GCP, US Code of Federal Regulations for Protection of Human Subjects (21 CFR 


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50.25[a,b], CFR 50.27, and CFR Part 56, Subpart A), the Health Insurance Portability and 
Accountability Act (HIPAA, if applicable), and local regulations.
The Investigator will prepare the informed consent form, assent and HIPAA authorization 
and provide the documents to the Sponsor or designee for approval prior to submission to 
the IRB/IEC.  The consent form generated by the Investigator must be acceptable to the 
Sponsor and be approved by the IRB/IEC.  The written consent document will embody the 
elements of informed consent as described in the International Conference on 
Harmonization and will also comply with local regulations. The Investigator will send an 
IRB/IEC-approved copy of the Informed Consent Form to the Sponsor (or designee) for 
the study file.
A properly executed, written, informed consent will be obtained from each subject prior to 
entering the subject into the trial.  Information should be given in both oral and written 
form and subjects (or their legal representatives) must be given ample opportunity to 
inquire about details of the study.  If appropriate and required by the local IRB/IEC, assent 
from the subject will also be obtained.  If a subject is unable to sign the informed consent 
form (ICF) and the HIPAA authorization, a legal representative may sign for the subject.   
A copy of the signed consent form (and assent) will be given to the subject or legal 
representative of the subject and the original will be maintained with the subject’s records.
16.4
Publications 
The preparation and submittal for publication of manuscripts containing the study results 
shall be in accordance with a process determined by mutual written agreement among the 
study Sponsor and participating institutions.  The publication or presentation of any study 
results shall comply with all applicable privacy laws, including, but not limited to, the 
Health Insurance Portability and Accountability Act of 1996. 
16.5
Investigator Responsibilities
By signing the Agreement of Investigator form, the Investigator agrees to:
1.
Conduct the study in accordance with the protocol and only make changes after 
notifying the Sponsor (or designee), except when to protect the safety, rights or 
welfare of subjects.
11
Personally conduct or supervise the study (or investigation).
12
Ensure that the requirements relating to obtaining informed consent and IRB review 
and approval meet federal guidelines, as stated in § 21 CFR, parts 50 and 56.
13
Report to the Sponsor or designee any AEs that occur in the course of the study, in 
accordance with §21 CFR 312.64.
14
Ensure that all associates, colleagues and employees assisting in the conduct of the 
study are informed about their obligations in meeting the above commitments.
15
Maintain adequate and accurate records in accordance with §21 CFR 312.62 and to 
make those records available for inspection with the Sponsor (or designee).
16
Ensure that an IRB that complies with the requirements of §21 CFR part 56 will be 


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responsible for initial and continuing review and approval of the clinical study.
17
Promptly report to the IRB and the Sponsor (or designee) all changes in the research 
activity and all unanticipated problems involving risks to subjects or others (to 
include amendments and IND safety reports).
18
Seek IRB approval before any changes are made in the research study, except when 
necessary to eliminate hazards to the patients/subjects.
19
Comply with all other requirements regarding the obligations of clinical investigators 
and all other pertinent requirements listed in § 21 CFR part 312.
17
References
Bell RJ, Lijovic M, La China M, Schwarz M, Fradkin P, Bradbury J, et al. Psychological well-
being in a cohort of women with invasive cancer nearly 2 years after diagnosis. Support Care 
Cancer 2010; 18: 921-9.
Busby MA, Stewart C, Miller CA, Grzeda KR, Marth GT. Scotty: a web tool for designing RNA-
Seq experiments to measure differential gene expression. Bioinformatics. 2013 Mar 1;29(5):656-7.
Gupta MA, Gupta AK. Depression and suicidal ideation in dermatology patients with acne, 
alopecia areata, atopic dermatitis and psoriasis. Br J Dermatol. 1998 Nov;139(5):846-50.
Hendriks AG, van der Velden HM, Wolberink EA, Seyger MM, Schalkwijk J, Zeeuwen PL et al. 
The effect of adalimumab on key drivers in the pathogenesis of psoriasis. Br J Dermatol. 
2014;170(3):571-80.
Johnston A, Guzman AM, Swindell WR, Wang F, Kang S, Gudjonsson JE. Early tissue responses 
in psoriasis to the anti-TNF- biologic etanercept suggest reduced IL-17R expression and 
signaling. Br J Dermatol. 2014; doi 10.111/bjd.12937.
Klocek M, Kubinyi A, Bacior B, Kawecka-Jaszcz K. Effect of physical training on quality of life 
and oxygen consumption in patients with congestive heart failure. Int J Cardiol 2005; 103: 323-9.
Krueger JG, Fretzin S, Suarez-Farinas M, Haslett PA, Phipps KM, Cameron GS et al. IL-17A is 
essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy 
Clin Immunol. 2012;130(1):145-54.
Kryczek I, Bruce AT, Gudjonsson JE, Johnston A, Aphale A, Vatan L et al. Induction of IL-17+ T 
cell trafficking and development by IFN-gamma: mechanism and pathological relevance in 
psoriasis. J Immunol. 2008;181(7):4733-41.
Li B, Tsoi LC, Swindell WR, Gudjonsson JE, Tejasvi T, Johnston A et al. Transcriptome analysis 
of psoriasis in large case-control sample: RNA-seq provides insights into disease mechanisms. J 
Invest Dermatol. 2014;134(7):1828-38.
Martin DA, Towne JE, Kricorian G, et al (2013)] The emerging role of IL-17 in the pathogenesis 
of psoriasis: preclinical and clinical findings. J Invest Dermatol; 133:17–26.
Matza LS, Boye KS, Yurgin N. Validation of two generic patient-reported outcome measures in 
patients with type 2 diabetes. Health Qaul Life Outcomes 2007; 5: 47.
Page SA, Verhoff MJ, Emes CG. Quality of life, bypass surgery, and the elderly. Can J Cardiol 
1995; 11: 777-82.
Perrott SB, Murray AH, Lowe J, Mathieson CM. The psychosocial impact of psoriasis: physical 


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severity, quality of life, and stigmatization.  Physiology and Behavior. 200 Sep15;70(5):567-71.
Russell CB, Rand H, Bigler J, Kerkof K, Timour M, Bautista E et al. Gene expression profiles 
normalized in psoriatic skin by treatment with brodalumab, a human anti-IL-17 receptor 
monoclonal antibody. J Immunol. 2014;192(8)3828-36.
Ryan C, Sadlier M, De Vol E, Patel M, Lloyd AA, Day A, et al. Genital psoriasis is associated 
with significant impairment in quality of life and sexual functioning. J Am Acad Dermatol. 2015 
Mar 27. Epub ahead of print.
Sanchez Rodriguez R, Pauli ML, Neuhaus IM, Yu SS, Arron ST, Harris HW et al. Memory 
regulatory T cells reside in human skin. J Clin Invest. 2014;124(3):1027-36.
Villanova F, Glutter B, Tosi I, Grys K, Sreeneebus H, Perera GK, et al. Characterization of innate 
lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis. J 
Invest Dermatol. 2014;134(4):984-91.
Villarino AV, Katzman SD, Gallo E, et al. Posttranscriptional silencing of effector cytokine 
mRNA underlies the anergic phenotype of self-reactive T cells. Immunity. 2011 Jan;34(1):50-60.
Zaba LC, Suarez-Farinas M, Fuentes-Duculan J, Nograles KE, Guttman-Yassky E, Cardinale I. 
Effective treatment of psoriasis with etanercept is linked to suppression of  IL-17 signaling, not 
immediate response TNF genes. J Allergy Clin Immunol 2009;124(5):1022-10.


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Protocol Template © CFFT TDN   Effective: 12 SEP 2007
APPENDIX 1.  EVALUATION SCHEDULE
Visit number
0
1
2
3
4
5
6
7
8
9
10
11
Time of Visit
Screen-
ing
wk 
0
wk 
1
wk 
2
wk 
3
wk 
4
wk 
8
wk 
12
wk 
16
wk 
24
wk 
36
wk 
52
Inclusion/Exclusion 
criteria
x
Informed consent
x
Review Medical 
History
x
Physical 
examination
x
x
x
x
x
Vital Signs
x
x
x
x
x
x
x
x
x
x
x
x
PASI and PGA
x
x
x
x
x
x
x
x
x
Laboratory 
assessments*
x
Urine Pregnancy 
x
x
x
x
x
x
x
x
x
Adverse events
x
x
x
x
x
x
x
x
x
x
x
Review con meds
x
x
x
x
x
x
x
x
x
x
x
x
Biopsy Procedures 
x
x
x
x
Photography
x
x
x
x
x
Dispense study 
medication
x
x
x
x
x
x
x
x
x
x
*CBC with differential, BUN, Cr, AST/ALT/Alk Phos, Hep B/C screening, Quantiferon Gold +/- CXR