An Open-label, Prospective, Non-randomized, Multicenter Study to Evaluate Clear Skin Effect on Health Related Quality of Life Outcomes at 16 and 52 Weeks in Patients With Moderate to Severe Plaque Psoriasis Treated With Secukinumab 300 mg s.c. With or Without Previous Exposure to Systemic Therapy.
Phase: PHASE4
Conditions: Plaque Psoriasis
Sponsor: Novartis Pharmaceuticals

Clinical Development – Medical Affairs Region Europe
Cosentyx®/Secukinumab/AIN457
Clinical Trial Protocol CAIN457A3401 / NCT02752776
An open-label, prospective, non-randomized, multicenter 
study to evaluate clear skin effect on health-related quality 
of life outcomes at 16 and 52 weeks in patients with 
moderate to severe plaque psoriasis treated with 
secukinumab 300 mg s.c. with or without previous 
exposure to systemic therapy
Authors:
 
Document type:
Clinical Trial Protocol 
EUDRACT number:
2015-003701-42
Version number:
v00 (Original protocol)
Development phase:
Phase 4
Release date:
21-Oct-2015
Property of Novartis
Confidential
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis
Clinical Trial Protocol Template Version 2.0, November, 2013

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Table of contents
Table of contents .................................................................................................................2
List of tables ........................................................................................................................5
List of figures ......................................................................................................................5
List of abbreviations............................................................................................................6
Glossary of terms.................................................................................................................8
Protocol summary................................................................................................................9
1
Introduction .......................................................................................................................16
1.1
Background............................................................................................................16
1.2
Purpose ..................................................................................................................18
2
Study objectives.................................................................................................................18
2.1
Primary objective...................................................................................................18
2.2
Secondary objectives .............................................................................................19
19
3
Investigational plan ...........................................................................................................20
3.1
Study design...........................................................................................................20
3.2
Rationale for study design .....................................................................................22
Rationale for conducting an interventional study..............................................................23
Rationale for selection of patient reported outcomes........................................................23
Rationale for selection of factors potentially impacting on skin efficacy and QoL 
outcomes................................................................................................................25
3.3
Rationale for dose/regimen, route of administration and duration of treatment....26
3.4
Rationale for choice of comparator .......................................................................27
3.5
Purpose and timing of interim analyses/design adaptations..................................27
3.6
Risks and benefits..................................................................................................27
4
Population..........................................................................................................................29
4.1
Inclusion criteria ....................................................................................................29
4.2
Exclusion criteria...................................................................................................30
5
Treatment...........................................................................................................................32
5.1
Study treatment......................................................................................................32
5.1.1
Investigational and control drugs..........................................................32
5.1.2
Additional treatment..............................................................................32
5.2
Treatment subpopulations......................................................................................33
5.3
Treatment assignment and randomization.............................................................33
5.4
Treatment blinding.................................................................................................34
5.5
Treating the patient................................................................................................34

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5.5.1
Patient numbering .................................................................................34
5.5.2
Dispensing the study drug.....................................................................34
5.5.3
Handling of study and additional treatment..........................................35
5.5.4
Instructions for prescribing and taking study treatment........................35
5.5.5
Permitted dose adjustments and interruptions of study treatment ........36
5.5.6
Rescue medication ................................................................................37
5.5.7
Concomitant medication .......................................................................37
5.5.8
Prohibited medication ...........................................................................38
5.5.9
Exposure to light ...................................................................................40
5.5.10
Emergency breaking of assigned treatment code..................................40
5.6
Study completion and discontinuation...................................................................40
5.6.1
Study completion and post-study treatment..........................................40
5.6.2
Discontinuation of study treatment .......................................................40
5.6.3
Withdrawal of informed consent...........................................................41
5.6.4
Loss to follow-up ..................................................................................41
5.6.5
Early study termination.........................................................................41
6
Visit schedule and assessments .........................................................................................42
Recommended visit windows............................................................................................43
Possible order of assessments:...........................................................................................43
6.1
Information to be collected on screening failures..................................................49
6.2
Patient demographics/other baseline characteristics .............................................49
6.2.1
Demographics .......................................................................................49
6.2.2
Psoriasis medical history / previous psoriasis therapies .......................49
6.2.3
Smoking history ....................................................................................50
6.2.4
Co-morbidities – cardiovascular medical history .................................50
6.2.5
Relevant medical history / current medical conditions.........................50
6.2.6
Prior and concomitant medications.......................................................50
6.2.7
Determination of tuberculosis status.....................................................50
6.2.8
Other Baseline characteristics...............................................................53
6.3
Treatment exposure and compliance .....................................................................53
6.4
Efficacy..................................................................................................................53
6.4.1
Investigator’s global assessment (IGA mod 2011) ...............................53
6.4.2
Assessment of psoriasis area and severity index (PASI) and total 
body surface area (BSA) .......................................................................54
6.4.3
Definitions of efficacy variables based on PASI ..................................55
6.4.4
Appropriateness of efficacy assessments..............................................56
6.5
Safety.....................................................................................................................56

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6.5.1
Physical examination ............................................................................56
6.5.2
Vital signs..............................................................................................56
6.5.3
Height, weight, waist and hip circumference........................................57
6.5.4
Laboratory evaluations..........................................................................57
6.5.5
Pregnancy and assessments of fertility .................................................58
6.5.6
Appropriateness of safety measurements..............................................58
6.6
Other assessments..................................................................................................58
6.6.1
Health-related quality of life.................................................................58
6.6.2
Resource utilization...............................................................................62
6.6.3
Pharmacokinetics ..................................................................................62
6.6.4
Other biomarkers...................................................................................62
7
Safety monitoring..............................................................................................................63
7.1
Adverse events.......................................................................................................63
7.2
Serious adverse event reporting.............................................................................65
7.3
Pregnancy reporting...............................................................................................65
8
Data review and database management.............................................................................66
8.1
Site monitoring ......................................................................................................66
8.2
Data collection.......................................................................................................66
8.3
Database management and quality control............................................................67
8.4
Data monitoring committee...................................................................................68
8.5
Adjudication committee.........................................................................................68
9
Data analysis......................................................................................................................68
9.1
Analysis sets ..........................................................................................................68
9.2
Patient demographics and other baseline characteristics.......................................68
9.3
Treatments .............................................................................................................68
9.3.1
Prior and concomitant medications.......................................................69
9.4
Analysis of the primary variable............................................................................69
9.4.1
Variable.................................................................................................69
9.4.2
Statistical model, hypothesis, and method of analysis..........................69
9.4.3
Handling of missing values/censoring/discontinuations.......................69
9.4.4
Sensitivity analyses ...............................................................................70
9.5
Analysis of secondary variables ............................................................................70
9.5.1
Efficacy variables..................................................................................70
Exploratory efficacy variables...........................................................................................70
9.5.2
Safety variables .....................................................................................70
9.5.3
Health-related quality of life.................................................................71

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9.5.4
Resource utilization...............................................................................71
9.5.5
Pharmacokinetics ..................................................................................71
9.5.6
Pharmacogenetics/pharmacogenomics .................................................71
9.5.7
Biomarkers............................................................................................71
9.5.8
PK/PD ...................................................................................................71
9.6
Interim analyses.....................................................................................................72
9.7
Sample size calculation..........................................................................................72
10 Ethical considerations........................................................................................................72
10.1
Regulatory and ethical compliance........................................................................72
10.2
Informed consent procedures.................................................................................72
10.3
Responsibilities of the investigator/qualified site staff and IRB/IEC....................73
10.4
Publication of study protocol and results...............................................................73
11 Protocol adherence ............................................................................................................73
11.1
Protocol amendments.............................................................................................73
12 References .........................................................................................................................74
13 Appendix 1: Clinically notable laboratory values and vital signs.....................................79
List of tables
Table 5-1
Overview of treatment during the study................................................33
Table 5-2
Prohibited medication ...........................................................................39
Table 6-1
Assessment schedule.............................................................................45
Table 6-2
Overview of study drug administration for Treatment Period 2...........49
Table 6-3
The IGA mod 2011 rating scale............................................................54
Table 6-4
The PASI scoring system......................................................................55
List of figures
Figure 3-1
Study design..........................................................................................21
Figure 6-1
Tuberculosis screening flowchart .........................................................52

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List of abbreviations
AE
Adverse Event
AIN457
Secukinumab
ALP
Alkaline Phosphatase
ALT
Alanine Aminotransferase
AST
Aspartate Aminotransferase
bpm
Beats per Minute
BSA
Body Surface Area
CHMP
Committee for Medicinal Products for Human Use
CRF
Case Report Form (paper or electronic)
CRO
Contract Research Organization
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Committee
DS&E
Drug Safety and Epidemiology
eCRF
Electronic Case Report Form
EMA
European Medicines Agency
EOT
End of Treatment 
EQ-5D
EuroQoL 5-Dimension Health Questionnaire©
GCP
Good Clinical Practice
H
Head (PASI scoring system)
hCG
Human Chorionic Gonadotropin
HAQ©-DI
Health Assessment Questionnaire©-Disability Index
HIV
Human Immunodeficiency Virus
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Conference on Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
IFU
Instructions for Use
IGA mod 2011
Novartis Investigator’s Global Assessment modified 2011

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IL
Interleukin
IN
Investigator Notification
IRB
Institutional Review Board
L
Lower limbs (PASI scoring system)
LLN
Lower Limit of Normal
LPFT
Last Patient First Treatment
MCID
Minimal Clinically Important Difference
MedDRA
Medical Dictionary for Regulatory Activities
NRS
Numeric Rating Scale
NYHA
New York Heart Association 
PASI
Psoriasis Area and Severity Index
PBI
Patient Benefit Index
PRO
Patient Reported Outcomes
PsA
Psoriatic Arthritis
PUVA
Psoralen Ultraviolet A
QFT
Quantiferon TB-Gold Test
QoL
Quality of Life
SAE
Serious Adverse Event
s.c.
Subcutaneous, subcutaneously
SUSAR
Suspected Unexpected Serious Adverse Reaction
T
Trunk (PASI scoring system)
TB
Tuberculosis
TCS
Topical Corticosteroid
TSQM
Treatment Satisfaction Questionnaire for Medication
U
Upper limbs (PASI scoring system)
ULN
Upper Limit of Normal
UV
Ultraviolet
UVB
Ultraviolet B
WBC
White Blood Cells
WHO
World Health Organization

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Glossary of terms
Assessment
A procedure used to generate data required by the study.
Enrollment
Point/time of patient entry into the study at which informed 
consent must be obtained prior to starting any of the procedures 
described in the protocol.
Medication number
A unique identifier on the label of each investigational/study drug 
package in studies that dispense medication using an electronic 
study system or commercially available study drug labelled 
according to local regulations will be used.
Protocol
A written account of all the procedures to be followed in a study, 
which describes all the administrative, documentation, analytical 
and clinical processes used in the study.
Premature patient withdrawal
Point/time when the patient exits from the study prior to the 
planned completion of all study drug administration and/or 
assessments; at this time all study drug administration is 
discontinued and no further assessments are planned unless the 
patient will be followed for progression and/or survival.
Study drug
Any single drug or combination of drugs administered to the 
patient as part of the required study procedures; includes 
investigational drug(s), active drug run-ins or background therapy.
Patient number 
A number assigned to each patient who enrolls into the study.
Variable
A measured value or assessed response that is determined in 
specific assessments and used in data analysis to evaluate the 
drug being tested in the study.

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Protocol summary
Protocol number
CAIN457A3401
Title
An open-label, prospective, non-randomized, multicenter study to 
evaluate clear skin effect on health-related quality of life outcomes at 16 
and 52 weeks in patients with moderate to severe plaque psoriasis 
treated with secukinumab 300 mg s.c. with or without previous exposure 
to systemic therapy.
Brief title
Study of effects of secukinumab on quality of life (QoL) in psoriasis 
patients with or without prior exposure to systemic therapy. 
Sponsor and Clinical 
Phase
Novartis, Phase IV 
Investigation type
Drug
Study type
Interventional
Purpose and rationale
Understanding the patient’s perspective on their disease and treatment is 
an important component of clinical research and medical practice. 
Secukinumab 300 mg s.c. is indicated for the treatment of moderate to 
severe plaque psoriasis in adults who are candidates for systemic 
therapy. Candidates for systemic therapy can be divided into 
3 sub-populations:

Subpopulation A: Patients who are naïve to any systemic 
treatment, e.g. patients failing or intolerant to previous topical 
treatment, including narrow band ultraviolet B (UVB) but never 
exposed 
to 
any 
systemic 
treatment, 
with 
or 
without 
contraindications to the use of conventional systemic treatment
and in need of a first systemic treatment.

Subpopulation B:
Patients who have been previously 
exposed to at least one conventional systemic therapy;
either because of failure or intolerance to their previous 
conventional systemic treatment, they are in need of first 
biologic systemic treatment.

Subpopulation C:
Patients who have been previously 
exposed to at least one biologic systemic therapy; either 
because of failure or intolerance to their previous biologic 
systemic treatment, they are in need of a different biologic 
systemic treatment.
The purpose of this patient centric study is to assess the impact of the 
exposure to a previous treatment prior to starting treatment with 
secukinumab 300 mg s.c. on QoL outcomes in relation to the highest skin 
efficacy response expected at Week 16 and the skin efficacy response at 
Week 52. The study population will consist of 3 pre-identified 
subpopulations (see above) and the overall population of these patients 
with moderate to severe plaque psoriasis. 
 
 
 

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Primary Objective

To assess the proportion of patients achieving a Dermatology 
Life Quality Index (DLQI) 0/1 response at Week 16 in 
3 pre-defined subpopulations and in the overall study population.
Secondary Objectives

To assess the proportion of patients achieving a DLQI 0/1 
response at Week 52 in 3 pre-defined subpopulations and in the 
overall study population.

To assess the effects of treatment with secukinumab 300 mg 
with respect to changes in EuroQoL 5-Dimension Health 
Questionnaire© (EQ-5D©), Health Assessment Questionnaire©-
Disability Index (HAQ©-DI), Numeric Rating Scale (NRS), 
Treatment Satisfaction Questionnaire for Medication (TSQM)
and Patient Benefit Index (PBI) response over time up to 
Week 16 and Week 52 compared to Baseline in 3 pre-defined 
subpopulations and in the overall study population.

To assess the proportion of patients achieving psoriasis area 
and severity index (PASI) 50, PASI 75, PASI 90, PASI 100 and 
Investigator’s Global Assessment modified 2011 (IGA mod 
2011) 0/1 responses at Week 16 and Week 52 in 3 pre-defined 
subpopulations and in the overall study population.

To assess the proportion of patients with DLQI scores 2-5, 6-10, 
11-20, 21-30 at Week 16 and Week 52 compared to Baseline in 
3 pre-defined subpopulations and in the overall study population.

To assess the overall safety and tolerability of treatment with 
secukinumab 300 mg in 3 pre-defined subpopulations and in the 
overall study population.

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Study design
This is an open-label, prospective, non-randomized, multicenter study of 
secukinumab 300 mg s.c. in patients with moderate to severe plaque 
psoriasis with or without previous exposure to systemic therapy. The 
study will take place across Europe in approximately 250 study centers in 
30 European countries. The study will be implemented in both 
hospital-based and office-based investigational sites. Secukinumab is 
intended for use under the guidance and supervision of a physician 
experienced in the diagnosis and treatment of psoriasis and whose 
center fulfills International Conference on Harmonization (ICH) Good 
Clinical Practice (GCP) quality requirements for the conduct of clinical 
trials. 
Population
The study population will consist of a representative group of male and 
female patients (≥18 years old) with moderate to severe plaque 
psoriasis. Moderate to severe plaque-type psoriasis is defined as a total 
PASI score of ≥ 10, IGA mod 2011 ≥ 3 and a body surface area (BSA)
≥10% at Baseline. Prior to entering the study, patients may either be 
naïve to systemic treatment (with or without contraindications to 
conventional systemic treatments) or have had prior exposure to any 
systemic therapy (conventional or biologic) used to treat their psoriasis.
Patients may have received topical treatment and narrow band UVB 
treatment prior to study entry.
Inclusion criteria

Patients must be able to understand and communicate with the 
Investigator and comply with the requirements of the study 
(including administration of secukinumab s.c. injections at home) 
and must provide written, signed and dated informed consent 
before any study related activity is performed. Where relevant, a 
legal representative will also sign the informed study consent 
according to local laws and regulations.

Men or women aged at least 18 years at time of Screening.

Moderate to severe plaque-type psoriasis diagnosed for at least 
3 months prior to Screening and candidate for systemic therapy.

Moderate to severe plaque-type psoriasis is defined at Baseline
by: 
-
PASI score ≥ 10 and
-
IGA mod 2011 score ≥ 3 and
-
BSA ≥ 10%

Candidate for systemic therapy is defined as a patient having 
moderate to severe plaque-type psoriasis that is inadequately 
controlled by:
-
Topical treatment (patients who were naïve to systemic 
treatments).
-
Phototherapy and/or previous systemic therapy (systemic 
therapy could be either conventional or biologic).
Exclusion criteria

Forms of psoriasis other than moderate to severe plaque-type
psoriasis, e.g. drug-induced psoriasis (i.e. new onset or current 
exacerbation from beta-blockers, calcium channel inhibitors or 
lithium) at Screening.

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
Patients with previous treatment with any agent targeting 
interleukin (IL)-17 directly or IL-17 receptor A (e.g. secukinumab, 
ixekizumab, or brodalumab).

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 human 
chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL).

Women of child-bearing potential, defined as all women 
physiologically capable of becoming pregnant unless they use 
effective contraception during the entire study or longer if 
required by locally approved prescribing information (e.g. 
20 weeks in EU). Barrier method: condom or occlusive cap 
(diaphragm or cervical/vault caps) with spermicide (where 
available). Note: 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 patient (periodic abstinence such as
calendar, ovulation, symptothermal, post-ovulation methods 
or
withdrawal 
are 
not 
acceptable 
methods 
of 
contraception). 
-
Female 
sterilization: 
have 
had 
a 
surgical 
bilateral 
oophorectomy (with or without hysterectomy) or tubal 
ligation at least 6 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 patients on the study, the 
vasectomized male partner should be the sole partner for 
that patient.
-
Use of established oral, injected or implanted hormonal 
methods of contraception, intrauterine device or intrauterine 
system post-ovulation methods).
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
-
6 months of spontaneous amenorrhea with serum FSH 
levels > 40 mIU/mL [for US only: and estradiol < 20 pg/mL] 
or
-
Surgical 
bilateral 
oophorectomy 
(with 
or 
without
hysterectomy) or tubal ligation at least 6 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 is she 
considered not of child bearing potential. 

Active ongoing inflammatory diseases other than psoriasis that 
might confound the evaluation of the benefit of secukinumab 
therapy. 

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
Underlying condition (including but not limited to metabolic, 
hematologic, renal, hepatic, pulmonary, neurologic, endocrine, 
cardiac, infectious or gastrointestinal), which in the opinion of the 
Investigator significantly immunocompromises the patient and/or 
places the patient at unacceptable risk for receiving an 
immunomodulatory therapy. Patients who are treated with 
secukinumab and have Crohn’s disease are eligible but should 
be followed closely.

Investigator discretion should be used for patients with 
preexisting or recent-onset central or peripheral nervous system 
demyelinating disorders. 

Significant medical problems including but not limited to the 
following: uncontrolled hypertension (systolic ≥160 mmHg 
and/or diastolic ≥95 mmHg), congestive heart failure (New York 
Heart Association (NYHA) status of class III or IV). 

Patients with a serum creatinine level exceeding 176.8 μmol/L 
(2.0 mg/dL). 

Screening total white blood cell (WBC) count < 2 500/μL, or 
platelets < 100 000/μL or neutrophils < 1 500/μL or hemoglobin 
< 8.5 g/dL. 

Active systemic infections during the last 2 weeks (exception: 
common cold) prior to Baseline and any infections that reoccur 
on a regular basis; Investigator discretion should be used 
regarding patients who have travelled or resided in areas of 
endemic mycoses, such as histoplasmosis, coccidioidomycosis 
or blastomycosis and for patients with underlying conditions that 
may predispose them to infection, such as advanced or poorly 
controlled diabetes. 

History of an ongoing, chronic or recurrent infectious disease or 
evidence of tuberculosis infection as defined by a positive or 
indeterminate QuantiFERON TB-Gold test (QFT) at Screening.
Patients with a positive or indeterminate QFT test may 
participate in the study if a full tuberculosis (TB) work-up 
(according to local practice/guidelines) completed within 
12 weeks prior to Day 1 (Baseline) establishes conclusively that 
the patient has no evidence of active TB. If presence of latent 
TB is established then treatment must have been initiated and 
maintained according to local country guidelines prior to Day 1 
(Baseline). 

Past medical history record of, or current infection with, human 
immunodeficiency virus (HIV), hepatitis B virus or hepatitis C 
virus prior to Baseline. 

History of lymphoproliferative disease or any known malignancy 
or history of malignancy of any organ system within the past 
5 years (except for Bowen’s disease of the skin, or basal cell 
carcinoma or actinic keratosis that have been treated with no 
evidence of recurrence in the past 12 weeks; carcinoma in situ 
of the cervix or non-invasive malignant colon polyps that have 
been removed).

Current severe progressive or uncontrolled disease, which in the 
judgment of the clinical Investigator renders the patient 
unsuitable for the study or puts the patient at increased risk (e.g. 
myocardial infarction within 26 weeks prior to Baseline). 

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
Inability or unwillingness to undergo repeated venipuncture 
(e.g. because of poor tolerability or lack of access to veins) or 
self-injection with pre-filled syringes (PFSs).

Patients who are allergic to rubber or latex or with history of 
hypersensitivity reactions to any of the excipients.

Any medical or psychiatric condition, which in the Investigator’s 
opinion would preclude the participant from adhering to the 
protocol or completing the study per protocol.

History or evidence of ongoing alcohol or drug abuse within the 
last 6 months before Baseline.

Plan for administration of live vaccines during the study period or 
6 weeks prior to Baseline.

Use of investigational treatment within 4 weeks before Baseline, 
or within a period of 5 half-lives of the investigational treatment, 
whichever is longer. 

Patients not willing to limit UV light exposure (e.g. sunbathing 
and/or the use of tanning devices) during the course of the 
study.
Investigational and 
reference therapy
Secukinumab 300 mg will be provided in 2 × 1 mL 150 mg secukinumab 
PFSs for s.c. injection. Secukinumab 300 mg (2 × PFSs of the 150 mg 
dose) will be self-administered by the patient at Baseline, once weekly at 
Weeks 1, 2 and 3, and thereafter at 4-weekly intervals starting from 
Week 4 until Week 16 (Treatment Period 1) or until Week 48 (Treatment 
Period 2). 
Patients will receive instructions for use (IFU) and training from study 
center staff on how to use and self-administer the study drug. The 
injections up to Week 16 and the subsequent ones occurring during a 
visit will be performed by the patient (or caregiver) at the study center, 
under the supervision of the study site staff. The injections not occurring 
during a study center visit will be performed by the patients (or caregiver) 
at their home. Training kits may be supplied by Novartis to study centers 
not familiar with use of PFS. 
Efficacy assessments

Investigator’s Global Assessment modified 2011 (IGA mod. 2011)

Psoriasis Area and Severity Index (PASI)

Body Surface Area (BSA)
Safety assessments

Adverse events

Vital signs (e.g. pulse rate, blood pressure)

Laboratory assessments (e.g. hematology, chemistry, urine tests)

Physical examination
Other assessments
Psoriasis / Psoriatic arthritis related questionnaires:

Numeric Rating Scale (NRS) - itching, scaling and pain visual analog 
scale (VAS)

Health Assessment Questionnaire©-Disability Index (HAQ©-DI for 
patients with concomitant PsA only)

Treatment Satisfaction Questionnaire for Medication (TSQM)

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
Patient Benefit Index (PBI)
Dermatology related questionnaires:

Dermatology Life Quality Index (DLQI)

General health related questionnaire:

EuroQoL 5-Dimension Health Status Questionnaire (EQ-5D©)
Data analysis
The primary analysis variable is the proportion of patients achieving a 
DLQI 0/1 response at Week 16 in subpopulations of patients with 
moderate to severe plaque psoriasis naïve to conventional systemic 
treatments, or previously exposed to at least one conventional or biologic 
systemic treatments for psoriasis, and in the overall study population. 
The primary analysis of this study will be purely descriptive without any 
formal group comparisons or hypothesis testing. For the proportions, 
(descriptive) 95% confidence intervals (CIs) will be reported additionally.
Key words
Plaque psoriasis, DLQI, EQ-5D©, 
HAQ©-DI, multicenter, NRS, 
PASI, PBI, psoriasis, QoL, secukinumab, TSQM

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1
Introduction
1.1
Background
Psoriasis is an immune-mediated, chronic relapsing inflammatory disease that mainly affects 
the skin and is characterized by variable clinical features. Plaque (also called plaque-type or 
chronic plaque) psoriasis is the most frequent clinical presentation. Chronic plaque psoriasis 
can have a profound impact on several aspects of a patient’s life. Psoriasis affects not only the 
skin itself but has been demonstrated to be closely related to the deterioration of patient’s 
emotional, social, occupational, and physical functioning (Eskin et al 2014). The impact of 
untreated chronic psoriasis on quality of life (QoL) has been demonstrated to be similar to the 
effects of cancer or congestive heart failure (Bhutani et al 2013). For these reasons, 
understanding the patient’s perspective on their psoriasis and impact on daily activities and 
disease treatment is a critical component of clinical research and practice. 
Broadly accepted assessment systems to measure the effect of psoriasis treatments on patients 
through a clinician-reported outcome are the Psoriasis Area and Severity Index (PASI) or the 
Investigator Global Assessment (IGA) (Feldman et al 2005; Langley et al 2013). The 
correlation between clinician-reported outcomes and patient-reported outcomes (PROs) has 
been studied to some extent (Revicki et al 2008); however, a better understanding from the 
view of the patient on the individual impact on the disease, influencing factors and effect of 
secukinumab during short and long term treatment is needed. Several PRO measures are 
available for psoriasis evaluation and are starting to be included as valuable endpoints in 
clinical trials (Gniadecki et al 2012, Revicki et al 2007, Lebwohl et al 2010, and Viswanathan 
et al 2014). A combination of general health-related, dermatology-related and psoriasis-
related questionnaires provides a comprehensive overview from different patient perspectives.
The EuroQOL 5-Dimension Health Questionnaire© (EQ-5D©) assesses each subject’s overall 
health status and is a standardized tool for measuring health outcomes. It has been extensively 
used in several dermatological conditions including psoriasis (Rønneberg Mehren et al 2014).
The tool was used during the Phase 3 clinical program for secukinumab.
The Dermatology Life Quality Index (DLQI) developed in 1994 (Finlay and Khan 1994), was 
the first dermatology-specific QoL instrument. Widely used (tested across >40 different skin 
conditions and available in > 90 languages, Basra et al 2008); it is a self-administered 
assessment of 6 domains: daily activities, leisure, personal relationships, symptoms and 
feelings, treatment, and work/school over the previous week. Several studies demonstrated a 
good correlation between the reduction in PASI score and the reduction in DLQI
(Vender et al 2012, Driessen et al 2010).  Secukinumab demonstrated clinically meaningful 
improvements in DLQI score in Phase 3 studies; however, the impact of previous psoriasis 
treatment on DLQI scoring has not yet investigated in depth. 
 
 
 
 
 

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In a large, multinational, population-based survey of psoriasis and/or PsA in North America 
and Europe, patients indicated that their most bothersome signs or symptoms were itching 
(43%) and scaling (23%) (Lebwohl et al 2014). The Numeric Rating Scale (NRS) is an 
11-point visual analog scale (VAS) used to evaluate the patient assessment of their main skin 
symptoms and signs such as itching, scaling and pain. 
Since psoriasis is an immune-mediated, chronic inflammatory disease, it may also result in 
systemic pathological effects. The severe forms have been associated with several diseases 
that have similar pathogenic factors. A comorbidity classically associated with psoriasis is 
psoriatic arthritis (PsA) (Moll et al 1973, Gladman 2004, Gladman et al 2005, Ibrahim et al 
2009). The Health Assessment Questionnaire©-Disability Index (HAQ©-DI) assesses the long 
term influence of chronic disease on functional ability and activity restriction in patients with 
a history of PsA (Fries et al 1982). Eighteen percent of patients in the Phase 3 program 
reported concomitant PsA at Baseline hence confirmation from a large study would be 
important.
Treatment success is highly influenced by patient satisfaction, as demonstrated by several 
studies investigating treatment satisfaction in psoriatic patients treated with biologics.
Although satisfaction with treatment was generally high, room for improvement was 
constantly detected in the “effectiveness” domain, which included the rapidity of onset of the 
clinical improvement in the “side-effects” and “convenience” domains of the Treatment 
Satisfaction Questionnaire for Medication (TSQM) (van Cranenburgh et al 2013, van den 
Reek et al 2014). The Patient Benefit Index (PBI) is a tool developed to assess patient relevant 
benefits in the treatment of psoriasis with a focus on perception of disease control; before 
treatment, the patient is asked about those benefits of treatment that are personally important 
to him/her; during or after treatment, the extent to which these patient-defined aims of 
treatment are being/were achieved is recorded (Feuerhahn et al 2012). Psoriasis is perceived 
by a significant number of patients as uncontrollable as well as incurable. This can trigger 
patient reactions such as anger or annoyance that might influence the perception of the 
treatment success (Linder et al 2009). Neither the TSQM nor PBI PROs were assessed during 
the Phase 3 clinical program for secukinumab.
Skin efficacy and QoL may be impacted by factors such as presence of co-morbidities
(Henseler et al 1995, Christophers 2007, Naldi et al 2010, Augustin et al 2010), the duration 
of the disease (Ros et al 2014), the localization of the plaques (Finlay and Coles 1995, O’Neill 
et al 1996, Touw et al 2001), and a concomitant treatment with topical medications for 
psoriasis (Heydendael et al 2004, Paul et al 2011, Albrecht et al 2011). A deeper knowledge 
of the relevance of these factors will help clinicians in better managing their patients and 
meeting patient expectations.
Secukinumab (AIN457) is a recombinant high-affinity fully human monoclonal anti-human 
interleukin-17A (IL-17A) antibody of the IgG1/κ-class. Secukinumab binds to human IL-17A 
and neutralizes the bioactivity of this cytokine. IL-17A is the central lymphokine of a newly 
defined subset of inflammatory T cells, the Th17 cells which, in several animal models, are 
pivotal in several autoimmune and inflammatory processes. IL-17A is mainly produced by 
memory effector CD4+ and CD8+ T lymphocytes (Lowes et al 2008; Kagami et al 2010). In 
the skin, this cytokine acts principally on keratinocytes to induce their activation and 
proliferation (Nestle et al 2009). A recent study showed that neutrophils may also be a 

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relevant source of the inflammatory cytokine IL-17A in psoriasis lesions (Reich et al 2015). 
IL-17A is being recognized as one of the principal pro-inflammatory cytokines in immune 
mediated inflammatory diseases. Its neutralization is expected to treat the underlying 
pathophysiology of immune mediated disease and as a consequence provide relief of 
symptoms (Patel et al 2013). An extensive Phase 2/3 program conducted in 3 430 patients 
demonstrated secukinumab to be very effective in treating plaque psoriasis, with 300 mg 
being the dose that delivered the most clinically meaningful benefit to patients with respect to 
achievement of almost clear to clear skin, improved QoL, speed of onset of action, and 
sustainability of symptom relief. From a safety perspective, secukinumab was well tolerated. 
Secukinumab was approved in the European Union (EU) in January 2015 for the treatment of 
moderate-to-severe plaque psoriasis in patients who are candidates for systemic therapy.
Systemic therapy includes conventional treatments, (e.g. cyclosporin, methotrexate, fumaric 
acid esters, acitretin, oral steroids, psoralen ultraviolet A (PUVA)) and biologic treatments 
(e.g. adalimumab, infliximab, etanercept, and ustekinumab). 
1.2
Purpose
Understanding the patient’s perspective on their disease and treatment is an important 
component of clinical research and medical practice. The purpose of this patient centric study 
is to assess whether patient QoL outcomes are impacted by the exposure to prior treatment 
prior to starting treatment with secukinumab 300 mg s.c. in relation to the highest skin 
efficacy response expected at Week 16 and the skin efficacy response at Week 52. Feedback 
from patients on QoL outcomes will be assessed using a combination of dermatology-related,
general health-related and psoriasis-related questionnaires: DLQI 
 
 EQ-5D© (overall health status); NRS (itching, scaling and pain
VAS); HAQ -DI (functional ability and activity restriction - only in patients with concomitant 
PsA); TSQM (treatment satisfaction) and PBI (treatment benefit). The use of these PROs was 
discussed and agreed with dermatologist and patient representatives.
 
 
 
 
 
Finally skin efficacy and QoL will be investigated to generate hypotheses on possible 
correlations of relevance. 
2
Study objectives
2.1
Primary objective

To assess the proportion of patients achieving a DLQI 0/1 response at Week 16 in 
3 pre-defined subpopulations and in the overall study population.

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2.2
Secondary objectives

To assess the proportion of patients achieving a DLQI 0/1 response at Week 52 in 
3 pre-defined subpopulations and in the overall study population.

To assess the effects of treatment with secukinumab 300 mg with respect to changes in
EQ-5D©, HAQ©-DI, NRS, TSQM and PBI response over time up to Week 16 and 
Week 52 compared to Baseline in 3 pre-defined subpopulations and in the overall study 
population.

To assess the proportion of patients achieving PASI 50, PASI 75, PASI 90, PASI 100 and 
IGA mod 2011 0/1 responses at Week 16 and Week 52 in 3 pre-defined subpopulations 
and in the overall study population.

To assess the proportion of patients with DLQI scores 2-5, 6-10, 11-20, 21-30 at Week 16 
and Week 52 compared to Baseline in 3 pre-defined subpopulations and in the overall 
study population.

To assess the overall safety and tolerability of treatment with secukinumab 300 mg in 
3 pre-defined subpopulations and in the overall study population.

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3
Investigational plan
3.1
Study design
The study will utilize an open-label, prospective, non-randomized but stratified multicenter 
study design. The study will take place across Europe, in approximately 250 study centers in 
30 European countries. The study will be implemented in both hospital-based and office-
based settings; secukinumab is intended for use under the guidance and supervision of a 
physician experienced in the diagnosis and treatment of psoriasis and whose center fulfills 
ICH Good Clinical Practice (GCP) quality requirements for the conduct of clinical trials
(CHMP/EWP/2454/02 corr).
Eligible patients will be categorized at Baseline according to previous exposure to treatment 
in one of the following 3 subpopulations: 

Subpopulation A: Patients who are naïve to any systemic treatment, e.g. patients failing 
or intolerant to previous topical treatment, including narrow band UVB, but never exposed 
to any systemic treatment, with or without contraindications to the use of conventional 
systemic treatment and in a need of a first systemic treatment.

Subpopulation B: Patients who have been previously exposed to at least one 
conventional systemic therapy; either because of failure or intolerance to their previous 
conventional systemic treatment, they are in a need of a first biologic systemic treatment;

Subpopulation C: Patients who have been previously exposed to at least one biologic 
systemic therapy; either because of failure or intolerance to their previous biologic 
systemic treatment, they are in a need of a different biologic systemic treatment.
All patients are scheduled to receive s.c. injections of secukinumab 300 mg at Week 0, 1, 2 
and 3 during the first 4 weeks followed by monthly maintenance dosing of 300 mg 
secukinumab starting at Week 4 until Week 48. Consideration should be given to 
discontinuing treatment in patients who have shown no response up to 16 weeks of treatment 
(e.g. patients who did not achieve a PASI 50 response). If discontinued, patients will complete 
the end of study visit assessments. Some patients with an initially partial response (e.g. 
patients who achieve a PASI 50 response but not a PASI 75 response) may subsequently 
improve with continued treatment beyond 16 weeks. 
The primary endpoint is the proportion of patients achieving a DLQI 0/1 response at Week 16 
in the 3 pre-defined subpopulations and in the overall study population. The study design is 
presented in Figure 3-1.

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Figure 3-1
Study design
Screening
Treatment Period 1
(Baseline to Week 16)
Treatment Period 2
(Week 16 to Week 52)
- 4 weeks
W0
W1
W2
W3
W4
W8
W12
W16
W20
W24
W28
W32
W36
W40
W44
W48
W52
Secukinumab 300 mg s.c.
Subpopulation A
Secukinumab 300 mg s.c.
Subpopulation B
Secukinumab 300 mg s.c.
Subpopulation C
Notes: The primary endpoint will be assessed at Week 16.
Subpopulation A: Patients who are naïve to any systemic treatment, e.g. patients failing or intolerant to previous topical treatment, including narrow band UVB, but 
never exposed to any systemic treatment, with or without contraindications to the use of conventional systemic treatment and in a need of a first systemic treatment.
Subpopulation B: Patients who have been previously exposed to at least one conventional systemic therapy; either because of failure or intolerance to their 
previous conventional systemic treatment, they are in a need of a first biologic systemic treatment;
Subpopulation C: Patients who have been previously exposed to at least one biologic systemic therapy; either because of failure or intolerance to their previous 
biologic systemic treatment, they are in a need of a different biologic systemic treatment.

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3.2
Rationale for study design
The pool of eligible patients affected by moderate to severe psoriasis is stratified into 
3 subpopulations to study whether a previous exposure to systemic treatments may have an 
effect on skin efficacy and QoL while on treatment with the same regimen of secukinumab 
300 mg as per the EU SmPC. Therefore, there is neither the need for blinding the study 
treatment nor to randomize the patients. In addition, the interest in this study is to assess how 
 
 
 
The inclusion of homogeneous subpopulations is needed in order to ensure sufficient power to 
detect clinically relevant outcomes in each category. 
The primary endpoint of this trial will be assessed at Week 16. This time point was chosen 
because the plateau of efficacy of treatment with secukinumab 300 mg was reached at 
16 weeks in the Phase 3 trials (see Section 1). A correlation between the PASI response and 
the DLQI response at Week 12 was already observed in the Phase 3 trials and it is also 
expected to be observed at Week 16 (DLQI response was not collected at Week 16 in the 
Phase 3 placebo-controlled trials). 
Secukinumab will be used according to the posology described in the EU SmPC. The 
recommended dose is 300 mg of secukinumab by subcutaneous (s.c.) injection with initial 
dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. 
Each 300 mg dose is given as 2 s.c. injections of 150 mg. Consideration will be given to 
discontinuing treatment in patients who have shown no response up to 16 weeks of treatment. 
Some patients with an initial partial response may subsequently improve with continued 
treatment beyond 16 weeks.
According to the EU S3 Guidelines on the systemic treatment of psoriasis vulgaris, the drugs 
that produce the highest PASI reduction by the end of induction therapy are also associated 
with the greatest reduction in DLQI (Katugampola et al 2007, Pathirana et al 2009). 
Furthermore, as the study design provides for a total treatment duration of 52 weeks, it also 
allows for the long-term assessment of the impact of the exposure to a previous treatment 
prior to start of treatment with secukinumab 300 mg s.c. on QoL outcomes and is aligned with 
the duration of the core Phase 3 trials.
Secukinumab was approved in the EU for the treatment of moderate-to-severe plaque
psoriasis in patients who are candidates for systemic therapy.
Systemic therapy includes conventional treatments, (e.g. cyclosporin, methotrexate, fumaric 
acid esters, acitretin, oral steroids, PUVA) and biologic treatments (e.g. adalimumab, 
infliximab, etanercept, and ustekinumab). Hence, candidates for systemic therapy may be 
divided into 3 different patient subpopulations:

Subpopulation A: Patients who are naïve to any systemic treatment, e.g. patients failing 
or intolerant to previous topical treatment, including narrow band ultraviolet B (UVB) but 
never exposed to any systemic treatment, with or without contraindications to the use of 
conventional systemic treatment and in need of a first systemic treatment.

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
Subpopulation B: Patients who have been previously exposed to at least one 
conventional systemic therapy; either because of failure or intolerance to their previous 
conventional systemic treatment, they are in need of first biologic systemic treatment.

Subpopulation C: Patients who have been previously exposed to at least one biologic 
systemic therapy; either because of failure or intolerance to their previous biologic 
systemic treatment, they are in need of a different biologic systemic treatment.
Feedback from patients on their QoL outcomes will be assessed using a combination of 
dermatology-related, general health-related and psoriasis-related questionnaires: DLQI 
 
; EQ-5D© (overall health status); NRS 
(itching, scaling and pain VAS); HAQ -DI (functional ability and activity restriction - only in 
patients with concomitant PsA); TSQM (treatment satisfaction) and PBI (treatment benefit). 
The selection of these PROs was discussed and agreed with dermatologist and patient 
representatives in order to provide meaningful data to characterize the patients’ perspective 
while keeping a reasonable burden on responders to questionnaires. 
Rationale for conducting an interventional study
An interventional study is required to introduce high quality standardizations for the trial 
conduct and to mitigate risks for data variability that could compromise the subsequent data 
analysis:

A mandatory treatment regimen of secukinumab 300 mg s.c. as per the EU SmPC
streamlines possible differences in the approved prescribing information of participating 
European countries.

Local medical assessment practices are also streamlined with regard to rules and processes 
for captured study outcomes and concomitant use of psoriasis medication (e.g. topical 
treatments).

It is necessary to harmonize the wash-out period for other systemic anti-psoriasis therapies 
prior to the start of the study to ensure robust data.

ICH GCP E6 guideline adherence during study conduct enables the collection of high 
quality data (e.g. completeness and correctness of data).
Rationale for selection of patient reported outcomes
The EQ-5D© assesses each subject’s overall health status and is a standardized tool for use as 
measure of health outcome. It has been extensively used in several dermatological conditions 
including psoriasis (Rønneberg Mehren et al 2014). It consists of a descriptive system of 
5 symptom domains, each with 3 response levels (no problems, some problems, severe 
problems), and the EQ-5D© VAS from 0 (worst possible health state) to 100 (best possible 
health state), both of which are completed by the subject. The EQ-5D© minimal important 
difference in psoriasis patients with body surface area (BSA) >5% is in the range of 3.82-8.43 
(Shikiar et al 2006). The tool was used during the Phase 3 clinical program for secukinumab.
Large improvements from Baseline were seen in the pain/discomfort domain, including 
extreme pain, and in the anxiety/depression domain for secukinumab compared to placebo 
and gains in overall health status from Baseline were seen versus placebo and etanercept at 
Week 12 (Study CAIN457A2302: +19.5 and +16.9 for 300 mg and 150 mg doses, -0.7 for 

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placebo; Study CAIN457A2303: +22.3 and +19.7 for 300 mg and 150 mg doses, +14.4 for 
etanercept, +2.2 for placebo).
The Dermatology Life Quality Index (DLQI) developed in 1994 (Finlay and Khan 1994), was 
the first dermatology-specific QoL instrument. Widely used (tested across >40 different skin 
conditions and available in >90 languages, Basra et al 2008), it is a self-administered 
assessment of 6 domains: daily activities, leisure, personal relationships, symptoms and 
feelings, treatment, and work/school over the previous one week. DLQI total scores range 
from 0 to 30 (sum of 10 questions, each ranging from 0 (not at all) to 3 (very much)) with 
higher scores indicating greater impairment in health-related QoL (HR-QoL). Several studies 
demonstrated a good correlation between the reduction in PASI score and the reduction in 
DLQI (Vender et al 2012, Driessen et al 2010). 
In a meta-analysis including randomized controlled trials of biological agents for the 
treatment of moderate-to-severe psoriasis, the authors highlighted how the achievement of a 
better DLQI response was greater in patients with >75% mean PASI reduction compared to 
those achieving a mean PASI reduction of 50–75% or below (Mattei et al 2014). Although 
PASI 75 is considered a meaningful cut-off, the European Medicines Agency (EMA)
Guidelines (CHMP/EWP/2454/02 corr) define treatment success on the basis of at least 90% 
improvement in PASI from Baseline. While the additional QoL benefit of achieving mean 
PASI reductions of 90% is intuitive, it still needs to be demonstrated. 
Results from the secukinumab Phase 3 program have shown that a large proportion of patients 
suffering from moderate to severe plaque psoriasis were able to achieve PASI 90 response at 
16 weeks, when treated with 300 mg s.c. (PASI 90 response rate up to 70%). The response 
rate was maintained up to Week 52 (PASI 90 response rate of 63%). In addition, 81.8% of 
patients with cleared or almost cleared skin at Week 24 maintained clear skin at Week 52 
(Callis et al 2014, Rich et al 2013, Sigurgeirsson et al 2014, Paul et al 2014). In Study
CAIN457A2303, secukinumab showed clear superiority over etanercept in both primary 
(PASI 75 and IGA 0/1) and secondary endpoints including the DLQI 0/1 assessment. 
Furthermore, an early onset of efficacy, based on 50% improvement in PASI scores was 
observed at Week 3 with secukinumab 300 mg s.c. compared to Week 8 with etanercept 
(Blauvelt et al 2015).
The Minimal Clinically Important Difference (MCID) of the DLQI in inflammatory skin 
diseases has been estimated in 5 studies in the range of 2.2-6.9 points (Langley et al 2014). In 
patients with psoriasis and on biologic therapy, a ≥ 5-point reduction in total DLQI score is 
considered the MCID (Augustin et al 2011). Mean decreases (improvements) in DLQI from 
Baseline were -11.5 and -10.1 for the secukinumab 300 mg and 150 mg doses versus -1.1 for 
placebo (p < 0.0001 for each dose versus placebo) in Study CAIN457A2302 at Week 12 
and -10.4 and -9.7 for secukinumab 300 mg and 150 mg, respectively, versus -7.9 for 
etanercept and -1.9 for placebo in Study CAIN457A2303 (p < 0.0001 for each dose versus 
either placebo or etanercept) at Week 12. Thus secukinumab demonstrated clinically 
meaningful improvements in DLQI score in both large studies, but whether a previous 
psoriasis treatment may impact on DLQI scoring has not yet deeply investigated. 
 

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In a large, multinational, population-based survey of psoriasis and/or PsA in North America 
and Europe patients indicated that their most bothersome signs or symptoms were itching 
(43%) and scaling (23%) (Lebwohl et al 2014). The NRS is an 11-point VAS used to evaluate 
the patient assessment of their main skin symptoms and signs such as itching, scaling and pain. 
Since psoriasis is an immune-mediated, chronic inflammatory disease, it may also result in 
systemic pathological effects. The severe forms have been associated with several diseases 
that have similar pathogenic factors. Psoriatic arthritis is a comorbidity classically associated 
with psoriasis (Moll et al 1973, Gladman 2004, Gladman et al 2005, Ibrahim et al 2009). The 
HAQ©-DI assesses the long term influence of chronic disease on functional ability and 
activity restriction in patients with a history of PsA (Fries et al 1982). The HAQ©-DI score 
can range from 0 to 3, with 0 indicating no disease, and 3 indicating worst possible disease. A 
change in score of 0.3 is usually considered clinically meaningful. The mean decrease 
(improvement) in HAQ©-DI from Baseline was greatest for the secukinumab 300 mg group at 
12 weeks (-0.38 and -0.18 for 300 mg and 150 mg secukinumab vs. -0.04 for placebo) and 
was sustained at 52 weeks (-0.39 and -0.20 for 300 mg and 150 mg secukinumab). For the 300 
mg dose, these results are clinically important (i.e. beyond the MCID) in this comorbid 
population and favor the 300 mg secukinumab dose. Eighteen percent of patients in the Phase 
3 program reported concomitant PsA at Baseline hence confirmation from a large study would 
be important.
Treatment success is highly influenced by patient satisfaction, as demonstrated by several 
studies investigating treatment satisfaction in psoriatic patients treated with biologics.
Although satisfaction with treatment was generally high, room for improvement was 
constantly detected in the “effectiveness” domain, which included the rapidity of onset of the 
clinical improvement in the “side-effects” and “convenience” domains of the TSQM
(van Cranenburgh et al 2013, van den Reek et al 2014).
The PBI is another tool developed to assess patient relevant benefits in the treatment of 
psoriasis: before treatment, the patient is asked about those benefits of treatment that are 
personally important to him/her; during or after treatment, the extent to which these patient-
defined aims of treatment are being/were achieved is recorded (Feuerhahn et al 2012). Both 
PROs, TSQM and PBI, were not assessed during the Phase 3 clinical program of secukinumab.
Rationale for selection of factors potentially impacting on skin efficacy 
and QoL outcomes
Compared to PsA, other comorbidities have been described as associated with psoriasis, 
including the metabolic syndrome as an independent risk factor for death and its individual 
components, which include arterial hypertension, adiposity and abnormalities in lipid and 
glucose metabolism (Henseler et al 1995, Christophers 2007, Naldi et al 2010, Augustin et al 
2010). This association is believed to account, at least partially, for the higher rate of 
cardiovascular complications observed among patients with psoriasis and contribute to the 
decreased life expectancy observed in patients with severe disease. Treatment of psoriasis has 

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the potential to significantly improve patient outcomes and possibly also protect against co-
morbidities (Reich 2012).
The burden of the physical and psychological comorbidities and stigma associated with 
psoriasis and the external factors and coping strategies modulated by the patient’s personality 
accumulated over the course of their lives may induce a progressive impairment in these 
patients, hence the duration of the disease is another important factor potentially impacting on 
the QoL (Ros et al 2014).
Several studies have demonstrated that plaques localization on visible body parts (legs, arms, 
and head) had a greater impact on the QoL than lesions located on other areas (Finlay and 
Coles 1995, O’Neill and Kelly 1996). It is also very likely that cosmetic disfigurement and 
itch may contribute to determining the burden of the illness (Touw et al 2001). For etanercept 
and adalimumab, data from post hoc analyses were published that suggested a similar 
sequential change in psoriasis symptom patterns in different body regions for treatment 
responders. Skin symptom improvements started from the head and trunk region in particular 
with improvement in desquamation and induration. Resolution of erythema and improvement
in plaques in the body region extremities, especially the lower extremities, were observed 
later (Griffiths et al 2015, Navarini et al 2012). A prospectively planned exploration on the 
dynamics of psoriasis symptom patterns once secukinumab treatment has started can deepen 
the understanding of symptom progress to better manage expectations of patients in daily 
medical practice.
Concomitant psoriasis treatments are very common in the management of moderate to severe 
psoriasis, with the aim to optimize the systemic treatment effect on the skin or when co-
morbidities are associated e.g. PsA (Heydendael et al 2004, Paul et al 2011). Examples of 
these co-medications are topical steroids, PUVA, emollients or a combination of these. Their 
concomitant use with a biologic treatment could have a significant impact on patient QoL and 
satisfaction (Albrecht et al 2011).
3.3
Rationale for dose/regimen, route of administration and duration 
of treatment
The efficacy and safety of secukinumab 300 mg s.c. for the treatment of moderate-to-severe 
plaque psoriasis has been demonstrated in the Phase 3 clinical program as described in 
Section 1. The 300 mg s.c. dose of secukinumab consistently delivered the most clinically 
meaningful benefit to patients compared to the 150 mg s.c. dose across all pivotal studies for 
all time points (Week 12 to Week 52) and the best risk/benefit profile as the safety profile of 
the 300 mg dose did not significantly differ from that of the 150 mg dose in the clinical 
program.
Pre-filled syringes (PFS) have been selected for secukinumab s.c. administration in this study 
as these have been successfully used by patients in the Phase 3 clinical trials (Blauvelt et al 
2015, Langley et al 2014), which showed the use of PFS was safe and well tolerated. 
Self-injection with the PFS, following the utilized instructions for use (IFU), showed no 
significant safety hazards and was found to be acceptable to study participants and to the 
competent authorities for other secukinumab studies (CAIN457A2312, CAIN4572313 and 
CAIN457A3301). Use of PFSs was approved by the EMA.

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Based on the results from the pivotal secukinumab Phase 3 studies in moderate to severe 
plaque psoriasis (CAIN457A2302 and CAIN457A2303), the plateau of efficacy was observed 
around Week 16; therefore, Week 16 has been selected as the time point for the core study, as 
described in Section 3.2.
A second treatment period will follow for an additional 36 weeks, bringing the total treatment 
period to 52 weeks, to provide continued treatment for patients who respond to treatment 
between Baseline and Week 16 (e.g. patients who achieved a PASI 75 response) and for 
patients who have an initial partial response to treatment between Baseline and Week 16 (e.g. 
patients who achieved a PASI 50 response but not a PASI 75 response; consideration should 
be given to discontinuing treatment in patients who have shown no response up to 16 weeks 
of treatment). The total treatment duration of 52 weeks is aligned with the treatment duration 
of the Phase 3 clinical studies.
Phase 3 studies in the secukinumab clinical program included a 12-week follow-up period, 
deemed necessary to evaluate the safety of secukinumab after the last dose administration. 
Considering that in this study the posology used is the one approved in the EU SmPC and no 
new safety signals are expected (Blauvelt et al 2015) such treatment free follow-up is not 
deemed necessary in this study protocol.
3.4
Rationale for choice of comparator
This study is designed primarily to assess whether the improvement of QoL, measured by the 
proportion of patients achieving a DLQI 0/1 response in patients with moderate to severe 
plaque psoriasis treated with secukinumab 300 mg s.c. varies within 3 subpopulations of 
patients naïve to or previously exposed to systemic treatments for psoriasis. Therefore, no 
placebo or other comparator treatment will be included in the study.
3.5
Purpose and timing of interim analyses/design adaptations
An interim analysis describing the self-reported Baseline characteristics and HR-QoL of 
patients prior to treatment may be performed for this study after last patient, first treatment 
(LPFT). Details will be described in the Statistical Analysis Plan (SAP).  
3.6
Risks and benefits 
Secukinumab has shown confirmed efficacy in psoriasis and preliminary efficacy in several 
inflammatory diseases, e.g. rheumatoid arthritis, ankylosing spondylitis, PsA: up to 12 000 
patients have been enrolled in studies with secukinumab with over 9 600 having received 
active drug at doses ranging from single and/or multiple doses of 0.1 mg/kg to 30 mg/kg i.v. 
and 25 mg to 300 mg s.c. An extensive Phase 2/3 program (conducted in 4 546 patients, 3 430 
of those treated with secukinumab) demonstrated secukinumab to be very effective in treating 
plaque psoriasis, with 300 mg being the dose that delivered the highest benefit to patients with 
respect to achievement of almost clear to clear skin, improved QoL, speed of onset of action, 
and sustainability of symptom relief. From a safety perspective, secukinumab was overall well 
tolerated. 
Secukinumab has the potential to increase the risk of infections. In clinical studies, infections 
have been observed in patients receiving secukinumab. Most of these were mild or moderate 

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upper respiratory tract infections such as nasopharyngitis and did not require treatment 
discontinuation.
Related to the mechanism of action of secukinumab, non-serious 
mucocutaneous Candida infections were more frequently reported for secukinumab than 
placebo in the psoriasis clinical studies (3.55 per 100 patient years for secukinumab 300 mg 
versus 1.00 per 100 patient years for placebo). Caution should be exercised when considering 
the use of secukinumab in patients with a chronic infection or a history of recurrent infection, 
and exclusion criteria are applied in this study to minimize the risk (Section 4.2). Patients will
be instructed to seek medical advice if signs or symptoms suggestive of an infection occur. 
If a patient develops a serious infection, the patient will be closely monitored and 
secukinumab should not be administered until the infection resolves. No increased 
susceptibility to tuberculosis was reported from clinical studies. However, secukinumab
should not be given to patients with active tuberculosis. Anti-tuberculosis therapy should be 
considered prior to initiation of secukinumab in patients with latent tuberculosis. Exclusion 
criteria are applied in this study to minimize the risk (Section 4.2) and additional guidance is 
provided in Section 6.2.7. 
Caution should be exercised when treating with secukinumab patients with Crohn’s disease as 
exacerbations of Crohn’s disease, in some cases serious, were observed in clinical studies in 
both secukinumab and placebo groups. Patients who are treated with secukinumab and have 
Crohn’s disease will be eligible but will be followed closely.
If an anaphylactic or other serious allergic reaction occurs, administration of secukinumab
should be discontinued immediately and appropriate therapy initiated.
The removable needle cap of the PFS contains a derivative of natural rubber latex. No natural 
rubber latex has to date been detected in the removable needle cap. Nevertheless, the use of 
secukinumab PFS in latex-sensitive individuals has not been studied and there is therefore a 
potential risk of hypersensitivity reactions, which cannot be completely ruled out. Exclusion 
criteria are applied in this study to minimize the risk (Section 4.2).
Live vaccines should not be given concurrently with secukinumab. Patients receiving 
secukinumab may receive concurrent inactivated or non-live vaccinations. In a study, after 
meningococcal and inactivated influenza vaccinations, a similar proportion of healthy 
volunteers treated with 150 mg of secukinumab and those treated with placebo were able to 
achieve an adequate immune response of at least a 4-fold increase in antibody titers to 
meningococcal and influenza vaccines. The data suggest that secukinumab does not suppress 
the humoral immune response to the meningococcal or influenza vaccines. Exclusion criteria 
are applied in this study to minimize the risk (Section 4.2).
Most of the experience to date has been with secukinumab s.c. doses up to 300 mg and i.v. 
doses up to 10 mg/kg; there are limited data at this time for higher doses. No cases of 
overdose have been reported for secukinumab. Single doses of secukinumab up to 30 mg/kg 
(i.e. approximately 2 000 to 3 000 mg) have been administered i.v. in clinical studies in other 
autoimmune indications, and doses up to 3 × 10 mg/kg i.v. have been administered in 
psoriasis studies without acute dose-limiting toxicity. 
Adverse events (AEs)/serious adverse events (SAEs) occurring during clinical trials with 
secukinumab should be managed based on the best clinical judgment of the Investigator in the 
context of the underlying disease and treated as clinically warranted. 

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Novartis standard processes aligned with international guidelines apply for the reporting of 
safety events.
Secukinumab 300 mg was approved in EU in January 2015 for the treatment of moderate to 
severe plaque psoriasis in adults who are candidates for systemic therapy on the basis of the 
Phase 2/3 program data. This Phase 4 study will be conducted in compliance with the 
requirements of Section 4.4, Warnings and Precautions of the EU SmPC). 
From the standpoint of the overall risk-benefit assessment, the current study with 
secukinumab is justified. 
Further details are provided in the EU SmPC and in the Investigator’s Brochure (IB) for 
secukinumab. 
4
Population
The study population will consist of a representative group of male and female patients (≥18 
years old) with moderate to severe plaque-type psoriasis. Moderate to severe plaque-type 
psoriasis is defined for this study by taking into consideration the European Psoriasis 
guideline (CHMP/EWP/2454/02 2004 corr), the published European Consensus (Mrowietz et 
al 2011) and the definition used in the Phase 3 clinical program. Hence, moderate to severe 
plaque-type psoriasis is defined by a total PASI score of ≥ 10, an IGA mod 2011 score ≥ 3 
and a BSA ≥ 10%. Prior to entering the study, patients may either be naïve to systemic 
treatment (with or without contraindications to conventional systemic treatments) or have 
previously been exposed to at least one systemic therapy (conventional or biologic) to treat 
their psoriasis.
4.1
Inclusion criteria
Patients eligible for inclusion in this study must fulfill all of the following criteria:
1. Patients must be able to understand and communicate with the Investigator and 
comply with the requirements of the study (including administration of s.c. injections 
at home) and must provide written, signed and dated informed consent before any 
study related activity is performed. Where relevant, a legal representative will also 
sign the informed study consent according to local laws and regulations.
2. Men or women aged at least 18 years at time of Screening.
3. Moderate to severe plaque-type psoriasis diagnosed for at least 3 months prior to 
Screening and candidate for systemic therapy.
Moderate to severe plaque-type psoriasis is defined at Baseline by: 

PASI score ≥ 10 and

IGA mod 2011 score ≥ 3 and

BSA ≥ 10%
Candidate for systemic therapy is defined as a patient having moderate to severe plaque-
type psoriasis that is inadequately controlled by:

Topical treatment (patients who were naïve to systemic treatments).

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
Phototherapy and/or previous systemic therapy (either conventional or biologic
systemic therapy).
4.2
Exclusion criteria
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No 
additional exclusions may be applied by the Investigator in order to ensure that the study 
population will be representative of all eligible patients.
The exclusion criteria are compliant with the information reported in the EU secukinumab 
PFS SmPC; however, additional criteria are used or additional details provided due to the 
study context (e.g. to allow appropriate assessment of efficacy or safety in accordance with 
ICH GCP requirements). 
1. Forms of psoriasis other than moderate to severe plaque-type psoriasis, e.g. drug-
induced psoriasis (i.e. new onset or current exacerbation from beta-blockers, calcium 
channel inhibitors or lithium) at Screening.
2. Patients with previous treatment with any agent targeting interleukin (IL)-17 directly 
or IL-17 receptor A (e.g. secukinumab, ixekizumab, or brodalumab).
3. 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 
human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL).
4. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant unless they use effective contraception during the entire study or 
longer if required by locally approved prescribing information (e.g. 20 weeks in EU). 
Barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) with 
spermicide (where available). Note: 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 patient (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 6 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 
patients on the study, the vasectomized male partner should be the sole partner 
for that patient.

Use of established oral, injected or implanted hormonal methods of 
contraception, intrauterine device or intrauterine system
post-ovulation 
methods).
NOTE: Women are considered post-menopausal and not of child bearing 
potential if they have had: 

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
12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile (e.g. age appropriate, history of vasomotor symptoms) or

6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL 
[for US only: and estradiol < 20 pg/mL] or

Surgical bilateral oophorectomy (with or without hysterectomy) or tubal 
ligation at least 6 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 is she considered not of 
child bearing potential. 
5. Active ongoing inflammatory diseases other than psoriasis that might confound the 
evaluation of the benefit of secukinumab therapy. 
6. Underlying condition (including but not limited to metabolic, hematologic, renal, 
hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal), 
which in the opinion of the Investigator significantly immunocompromises the patient
and/or places the patient at unacceptable risk for receiving an immunomodulatory 
therapy. Patients who are treated with secukinumab and have Crohn’s disease are 
eligible but should be followed closely.
7. Investigator discretion should be used for patients with preexisting or recent-onset 
central or peripheral nervous system demyelinating disorders. 
8. Significant medical problems including but not limited to the following: uncontrolled 
hypertension (systolic ≥160 mmHg and/or diastolic ≥95 mmHg), congestive heart 
failure (New York Heart Association (NYHA) status of class III or IV). 
9. Patients with a serum creatinine level exceeding 176.8 μmol/L (2.0 mg/dL). 
10. Screening total white blood cell (WBC) count < 2 500/μL, or platelets < 100 000/μL 
or neutrophils < 1 500/μL or hemoglobin < 8.5 g/dL. 
11. Active systemic infections during the last 2 weeks (exception: common cold) prior to 
Baseline and any infections that reoccur on a regular basis; Investigator discretion 
should be used regarding patients who have travelled or resided in areas of endemic 
mycoses, such as histoplasmosis, coccidioidomycosis or blastomycosis and for 
patients with underlying conditions that may predispose them to infection, such as 
advanced or poorly controlled diabetes. 
12. History of an ongoing, chronic or recurrent infectious disease or evidence of 
tuberculosis infection as defined by a positive or indeterminate QuantiFERON 
TB-Gold test (QFT) at Screening. Patients with a positive or indeterminate QFT test 
may participate in the study if a full tuberculosis (TB) work-up (according to local 
practice/guidelines) completed within 12 weeks prior to Day 1 (Baseline) establishes 
conclusively that the patient has no evidence of active TB. If presence of latent TB is 
established then treatment must have been initiated and maintained according to local 
country guidelines prior to Day 1 (Baseline).
13. Past medical history record of, or current infection with, human immunodeficiency 
virus (HIV), hepatitis B virus or hepatitis C virus prior to Baseline. 
14. History of lymphoproliferative disease or any known malignancy or history of 
malignancy of any organ system within the past 5 years (except for Bowen’s disease
of the skin, or basal cell carcinoma or actinic keratosis that have been treated with no 

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evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-
invasive malignant colon polyps that have been removed).
15. Current severe progressive or uncontrolled disease, which in the judgment of the 
clinical Investigator renders the patient unsuitable for the study or puts the patient at 
increased risk (e.g. myocardial infarction within 26 weeks prior to Baseline). 
16. Inability or unwillingness to undergo repeated venipuncture (e.g. because of poor 
tolerability or lack of access to veins) or self-injection with the PFS.
17. Patients who are allergic to rubber or latex or with history of hypersensitivity reactions 
to any of the excipients.
18. Any medical or psychiatric condition, which in the Investigator’s opinion would 
preclude the participant from adhering to the protocol or completing the study per 
protocol.
19. History or evidence of ongoing alcohol or drug abuse within the last 6 months before 
Baseline.
20. Plan for administration of live vaccines during the study period or 6 weeks prior to 
Baseline.
21. Use of investigational treatment within 4 weeks before Baseline, or within a period of 
5 half-lives of the investigational treatment, whichever is longer. 
22. Patients not willing to limit UV light exposure (e.g. sunbathing and/or the use of 
tanning devices) during the course of the study.
5
Treatment
5.1
Study treatment
5.1.1
Investigational and control drugs
The same investigational treatment will be given to all patients recruited in the 
3 subpopulations: secukinumab/AIN457 300 mg s.c. as per EU-approved SmPC. No reference 
therapy will be given.
Secukinumab for s.c. injection will be supplied in single boxes each containing prefilled 
syringes (PFS) of 150 mg secukinumab in a 1 mL liquid formulation. The study drug supplies 
will be open label. Secukinumab 300 mg (2 × PFS of the 150 mg dose) will be 
self-administered by the patient at Baseline, Weeks 1, 2, 3, 4, 8, and 12 during Treatment 
Period 1 and at Week 16, 20, 24, 28, 32, 36, 40, 44 and 48 during Treatment Period 2.
Patients will receive instructions and training from study center staff on how to use and 
self-administer the study drug. The injections up to Week 16 and the subsequent ones 
occurring during a visit will be performed by the patient (or caregiver) at the study center, 
under the supervision of the investigational site staff. The injections not occurring during a 
study center visit will be performed by the patient (or caregiver) at their home. 
5.1.2
Additional treatment
No additional treatment other than the investigational drug will be provided for this study.

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5.2
Treatment subpopulations
Eligible patients will be stratified at Baseline according to previous exposure to treatment in 
3 subpopulations: 

Subpopulation A: 646 patients who are naïve to any systemic treatment, e.g. patients 
failing or intolerant to previous topical treatment, including narrow band ultraviolet B 
(UVB) but never exposed to any systemic treatment, with or without contraindications to 
the use of conventional systemic treatment and in need of a first systemic treatment.

Subpopulation B: 646 patients who have been previously exposed to at least one 
conventional systemic therapy; either because of failure or intolerance to their previous 
conventional systemic treatment, they are in need of first biologic systemic treatment.

Subpopulation C: 323 patients who have been previously exposed to at least one 
biologic systemic therapy; either because of failure or intolerance to their previous 
biologic systemic treatment, they are in need of a different biologic systemic treatment.
All patients will be assigned to receive the same treatment regimen:

Secukinumab 300 mg regimen: Secukinumab 300 mg s.c. (supplied in single boxes 
each containing 2 × PFS of the 150 mg dose for s.c. injection) self-administered at 
Baseline, once weekly at Week 1, 2 and 3, and thereafter at 4-weekly intervals 
starting Week 4 until Week 48 inclusive. 
The treatment administration schedule is presented in Table 5-1 and the treatment 
administration schedule is presented in Table 6-2. 
Table 5-1
Overview of treatment during the study
Treatment Period 1 (Baseline to Week 16)
(Self-administration at Study Center)
(Self-administration at Home)
Baseline &
Weeks 1, 2, 3, 4, 8, and 12 
None
Treatment Period 2 (Week 16 to Week 52)
(Self-administration at Study Center)
(Self-administration at Home)
Week 16, 20, 24, 36 and 48
Week 28, 32, 40 and 44
5.3
Treatment assignment and randomization 
This is a non-randomized, single regimen study. At the Screening Visit, every patient will be 
registered in an electronic study system. The Investigator or his/her delegate will check that 
the patient fulfills all the inclusion/exclusion criteria before assigning study drug to the patient. 
At Baseline, eligible patients will be stratified according to previous exposure to treatment in 
3 subpopulations as described above (Section 5.2).
To ensure that recruitment of patients fulfils the required sample size for each of the 
subpopulations the electronic study system will indicate the stop of the allocation to a 

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subpopulation when the planned number of patients is achieved in the respective 
subpopulation.
5.4
Treatment blinding
This is an open-label, single regimen study; the study drug will not be blinded. 
5.5
Treating the patient
Sponsor qualified medical personnel will be readily available to advise on trial related 
medical questions or problems.
5.5.1
Patient numbering
Each patient is uniquely identified by a Patient Number, which is composed of the study 
center number assigned by Novartis and a sequential number assigned by the Investigator. 
Once assigned to a patient, the Patient Number will not be reused. 
Upon signing the informed consent form (ICF), the patient is assigned the next sequential 
number by the Investigator. The Investigator or his/her staff will contact the electronic study 
system and provide the requested identifying information for the patient to register them into 
the study. The study center should select the case report form (CRF) book with a matching 
Patient Number from the data capture system to enter data. 
If the patient fails to be treated for any reason, the electronic study system must be notified 
that the patient was not treated. The reason for not being treated will be entered in the CRF.
5.5.2
Dispensing the study drug
Each study site will be supplied by Novartis with study drug in packaging of similar 
appearance depending on the commercial availability of the study drug. The study drug 
packaging has either a 2-part label or commercially available drug will be used following 
local requirements. Investigator staff will select the study drug to dispense to the patient after 
successful registration of the patient in the electronic study system. If applicable, immediately 
before dispensing study drug to the patient, Investigator staff will detach the outer part of the 
label from the packaging and affix it to the source document (Drug Label Form) for that 
patient’s unique Patient Number or drug accountability records for the commercially available 
kits must be completed to allow traceability.
From Week 28, once the home study drug administration applies, patients will be expected to 
perform home drug administrations at the protocol specified time-points. For these cases, the 
Investigator will dispense, supported by the electronic study system, an appropriate number of 
investigational treatment packages for home administrations. The patients will record details 
including the date of administration at home in a self-administration log and will return the 
used medication (if in compliance with local rules and guidelines) and medication packaging, 
together with the self-administration log, at their next visit to the study center. Patients will be 
asked to return all unused study drug and packaging at each scheduled study visit and by the 
very latest at the end of the study. 

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5.5.3
Handling of study and additional treatment
5.5.3.1
Handling of study treatment
The study drug must be received by appropriate personnel at the study center, handled and 
stored safely and properly, and kept in a secured location to which only appropriate study
personnel have access. Upon receipt, all study drugs should be stored according to the local 
process instructions. Clinical supplies are to be dispensed only in accordance with the 
protocol. Technical complaints are to be reported as per Novartis processes.
The PFS sealed in their outer box must be stored in a locked refrigerator between 2°C and 8°C 
(36°F and 46°F) and must be carefully controlled in accordance with regulations governing 
investigational medicinal products, local regulations and in accordance with instructions from
the Novartis Drug Supply Management or Novartis Drug Supply Chain or corresponding 
service providers. The study drug should be protected from the light and must not be frozen.
Study drug labels, if applicable, will be in the local language and comply with the legal 
requirements of each country. They will include storage conditions for the study drug 
including the study drug number.
The Pharmacist, Investigator, or other qualified study center personnel must maintain an 
accurate record of the shipment and dispensing of the study drug. Monitoring of drug 
accountability will be performed by the field monitor continuously during study center visits 
and finally reconciled at the completion of the study. 
Patients will be asked to return all used study drug (if possible according to local guidelines 
and practice), unused study drug and packaging at the following visit but latest at the end of 
the study or at the time of discontinuation of study drug. 
At the conclusion of the study, and as appropriate during the course of the study, study drug 
documentation will be archived by site personnel and by the Novartis monitor or similar study 
function as per Novartis processes.
5.5.3.2
Handling of additional treatment 
Not applicable.
5.5.4
Instructions for prescribing and taking study treatment 
Patients will self-administer secukinumab by s.c. injection using a PFS. Each 300 mg dose 
will consist of 2 × 150 mg s.c. injections of 1 mL each. The dosing frequency will be either 
weekly or every 4 weeks in accordance with the administration schedule (Table 5-1 and Table 
6-2). The last dose administration will occur at Week 48. 
Patients will receive instructions and training from study center staff on how to 
self-administer the study drug. The injections up to Week 16 and the subsequent ones 
occurring during a visit will be done by the patient (or caregiver) at the study center, under the 
supervision of the Investigator or study staff (at Baseline, Weeks 1, 2, 3, 4, 8, and 12 during 
Treatment Period 1; and Week 16, 20, 24, 36 and 48 during Treatment Period 2).
The patient will be instructed on the use of secukinumab via review of IFU for secukinumab 
PFS (PFS-IFU). At subsequent visits, the Investigator/qualified study center staff will observe 

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the self-administration of secukinumab at the clinic. The injections not occurring during a 
study center visit will be done by eligible patients (or caregiver) at their home (Weeks 28, 32, 
40 and 44) during Treatment Period 2.
All dosages prescribed and dispensed to the patient during the study must be recorded in the 
eCRF. 
The patient will document all doses, dates and times of self-administration at home in a 
self-administration log. Patients are required to return the self-administration log at every visit 
to the study center.
The Investigator should promote compliance by instructing the patient to take the study drug
exactly as prescribed and by stating that compliance is necessary for the patient’s safety and 
the validity of the study. The patient should be instructed to contact the Investigator if he/she 
is unable for any reason to take the study drug as prescribed.
At the beginning of the study, the Investigator/qualified study center staff will determine if 
self-administration is appropriate for the patient, e.g. manual dexterity, ability to follow the 
secukinumab PFS-IFU. If a patient requires a caregiver to administer study drug, the caregiver 
should be trained by the Investigator/qualified study center staff. If a caregiver is not available 
at a particular visit or the patient is having problems with self-administration, the 
Investigator/qualified study center staff may administer the study drug to the patient. However, 
all patients should be trained sufficiently and be comfortable with the study drug self-
administration before the first home administration visit. Patients should be instructed to 
contract the Investigator site staff in case of any issue during study drug home administration. 
Records of study drug kits assigned to the patient during the study must be documented. 
At each visit, all study assessments, including the completion of PROs, should be completed 
prior to self-injection of the study drug.
5.5.5
Permitted dose adjustments and interruptions of study treatment
In general, treatment interruptions are not permitted. No dose adjustment of study drug is 
permitted and no interruption of the study drug should be planned during the study, with the 
following exceptions.
For patients who are unable to tolerate the protocol-specified dosing scheme, dose 
interruptions of study drug are permitted in order to keep the patient on study drug. The 
following guidelines should be followed:

Study drug interruption is permitted if, in the opinion of the Investigator, a patient is 
deemed to be placed at a safety risk unless dosing is temporarily interrupted. In such cases 
study drug should be interrupted only during the time that this risk is present and ongoing. 
Study drug can be started again at the next scheduled visit after resolution of the safety 
risk.

The effect of secukinumab on live vaccines is unknown; therefore, live vaccines should 
not be administered during participation in the study. If the patient received a live virus 
vaccination during the study, the patient must discontinue study drug and complete the 
end-of-study visit.

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If a dose of secukinumab was dispensed by the electronic study system but not administered 
to a patient, this deviation event must be recorded in the CRF.
5.5.6
Rescue medication
Rescue medication is not permitted in this study.
As per the EU-approved SmPC, consideration should be given to discontinuing treatment in 
patients who have shown no response up to 16 weeks of treatment. Some patients with 
initially partial response may subsequently improve with continued treatment beyond 
16 weeks.
5.5.7
Concomitant medication
All treatments administered during the 6 months prior to start of study drug (including any
treatments started during the Screening period) for any reason NOT including psoriasis will 
be entered in the eCRF. The start date, end date, dose, unit, frequency, route and reason for 
administration should be recorded. 
In addition, psoriasis treatments used from the time the patient started psoriasis treatment will 
be reported in the eCRF. All topical treatments, systemic treatments and phototherapies for 
psoriasis administered will be entered in the eCRF (Section 6.2.2).
The Investigator/qualified study center staff should instruct the patient to notify the study 
center about any new medications that he/she takes after being enrolled into the study. All 
medications, procedures and significant non-drug therapies (including physical therapy and 
blood transfusions) administered after the patient starts study drug must be recorded on the 
appropriate eCRF page. 
5.5.7.1
Permitted concomitant medications (not for psoriasis or psoriatic 
arthritis)
Concomitant medications are allowed if not listed in Table 5-2. Dose adjustments of these 
medications should be avoided during the study. If a dose adjustment of these medications 
does occur, it must be recorded on the appropriate eCRF page. There is no restriction on the 
use of topical corticosteroids (TCS) different from treatment of psoriasis but their use must be 
recorded under the Concomitant Medications eCRF.
There is no restriction on the use of anti-histamines or corticosteroid drops (for use in the eye 
or ear) during the study.
5.5.7.2
Permitted concomitant medications for psoriasis
After the Screening period, the use of concomitant emollients (not supplied by Novartis) or 
other non-medicated interventions (not listed in Table 5-2) for psoriasis affecting all body 
regions is allowed. Use of emollients must be recorded on the concomitant medications eCRF. 
Use of any other non-medicated interventions must also be recorded in the eCRF.
Use of emollients is recommended as a first line intervention but TCS are allowed as a second 
line intervention for the treatment of plaques at the discretion of the Investigator during the 
treatment periods. Use of mild potent TCS for limited periods (e.g. up to 7 consecutive days) 

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is recommended as the first step whilst use of moderate to potent TCS should be considered as 
the last step, at the discretion of the Investigator. Use of these TCS therapies will be recorded 
on appropriate eCRF pages including the reason for usage.
5.5.7.3
Permitted concomitant medications for psoriatic arthritis
The use of non-steroidal anti-inflammatory drugs, analgesics or any other medications used to 
treat PsA will be permitted only if not listed in Table 5-2. Use of these medications must be 
recorded on the appropriate eCRF page.
Dose adjustments of these medications should be avoided during the study. If a dose 
adjustment of these medications should occur, it must be recorded in the eCRF.
5.5.8
Prohibited medication
Use of any treatments displayed in Table 5-2 that could confound the efficacy of secukinumab 
are NOT allowed during the study for any indication and wash-out periods for these 
treatments are indicated in Table 5-2. If the use of these treatments is required, then the 
patient must NOT be enrolled into the study. 
The Investigator/qualified study center staff must instruct the patient to notify them about any 
new treatments the patient takes after the start of the study drug. All prohibited medications 
and significant non-drug therapies administered after the patient starts study drug must be 
recorded in the eCRF. 
If a prohibited medication listed in Table 5-2 is used during the study, the patient must 
discontinue use of the prohibited medication if he/she wishes to continue in the study. At the 
discretion of the Investigator/qualified study center staff, if the patient’s use of a prohibited 
medication listed in Table 5-2 presents undue safety risk for the patient, the patient should be 
discontinued from study drug as per Section 5.6.2. 
If the patient received a live virus vaccination during the study, the patient must discontinue 
study drug and complete the end-of-study visit.
Any other protocol deviation that results in a significant risk to the patient’s safety will be 
recorded. 

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Table 5-2
Prohibited medication
Prior Therapy (before Baseline Visit [Day 1])
Prohibited medications†, ‡ 
Washout period 
(before Baseline Visit 
[Day 1])
Any biologic drug directly targeting IL-17 or the IL-17RA (e.g.
secukinumab, ixekizumab or brodalumab)
No prior use allowed
Alefacept, briakinumab, efalizumab, ustekinumab 
6 months
Biological immunomodulating agents other than above 
(e.g. etanercept, adalimumab, infliximab)
12 weeks
Other systemic immunomodulating treatments§
(e.g. methotrexate, cyclosporine A, corticosteroids (oral, i.v., 
intramuscular, s.c., intra-articular, transdermal)§, cyclophosphamide)
4 weeks
Other systemic psoriasis treatments (e.g. apremilast, retinoid, 
fumarates)
4 weeks
Photo chemotherapy (e.g. PUVA) 
4 weeks
Phototherapy (e.g. UVA, UVB) 
2 weeks
Live virus vaccinations
6 weeks
Any investigational treatment or participation in any interventional 
study
4 weeks or 5 half-lives 
(whichever is longer)
Prior Therapy (before Baseline Visit)
Stable period
(before Baseline Visit 
[Day 1])
Any other treatment known to worsen psoriasis (e.g. beta-blockers, 
calcium channel blockers, lithium)
Stable at least 4 weeks 
before Baseline Visit 
(Day 1)
Abbreviations: PUVA: psoralen ultraviolet A; UVA: ultraviolet A; UVB: ultraviolet B
† If the prohibited treatment was used during the study for any indication, the patient must discontinue 
use of the prohibited treatment if he/she wishes to continue in the study. 
‡ In case of undue safety risk for the patient, the patient should discontinue the study drug at the 
discretion of the Investigator/qualified study center staff. If the patient received a live virus vaccination 
during the study, the patient must discontinue the study drug.
§ Inhalative corticosteroids with only a topical effect (e.g. to treat asthma) and topical corticosteroids for 
ocular use (e.g. eye drops) are not considered “systemic immunomodulating treatments” and are 
therefore acceptable for use as comedication. 

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5.5.9
Exposure to light
Patients need to be advised to limit exposure to UV light (including extensive sunbathing 
and/or use of UV tanning devices) during the study to avoid possible effects on psoriasis.
5.5.10
Emergency breaking of assigned treatment code
Not applicable.
5.6
Study completion and discontinuation
5.6.1
Study completion and post-study treatment 
Study completion is defined as all patients who have been enrolled at Baseline and completed 
the study as described in the protocol.
The Investigator must provide follow-up medical care for all patients who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care.
5.6.2
Discontinuation of study treatment
If discontinuation occurs for any reason in a treatment period (i.e. Treatment Period 1 or 2), 
the Investigator/qualified site staff must make every effort to determine the primary reason for 
the patient’s discontinuation from the study. This information will then be recorded by 
Investigator/qualified site staff in the applicable eCRF section. 
The study drug must be discontinued under the following circumstances:

Withdrawal of informed consent.

Emergence of the following AEs: AEs that in the judgment of the Investigator/qualified 
site staff (taking into account the patient’s overall status) prevent the patient from
continuing participation in the study (for example, sepsis or serious infection).

Any laboratory abnormalities that in the judgment of the Investigator/qualified site staff 
(taking into consideration the patient’s overall status) prevents the patient from continuing 
participation in the study.

Pregnancy (see Section 6.5.5 and Section 7.3).

Use of prohibited treatment as per guidance in Section 5.5.8.

Any other protocol deviation that results in a significant risk to the patient’s safety.
Patients discontinued from study drug will NOT be considered discontinued from the study. 
On the applicable section of the eCRF, the Investigator/qualified site staff must record the 
date and primary reason for stopping the study drug.
At the time of the study drug discontinuation visit, 

IF it has been at least 4 weeks after the last dose of study drug, THEN the assessments 
described for the end of Treatment Period 1 (EOT1) visit/Week 16 (for early 
discontinuation during Treatment Period 1) or the end of the Treatment Period 2 (EOT2) 
visit/Week 52 (for early discontinuation during Treatment Period 2) should be completed 
at this visit. 

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
IF it has not been at least 4 weeks after the last dose of study drug at the time of the study 
drug discontinuation visit, THEN the patient should be scheduled to return 4 weeks post 
last dose for their EOT1 visit (Week 16) or EOT2 visit (Week 52) assessments, 
respectively. 
The Investigator/qualified site staff must contact the electronic study system on every study 
visit including when the patient completes the EOT1 visit (Week 16) or EOT2 Visit (Week 
52) assessments to register the patient’s completion of the study (Treatment Period 1 or 2, 
respectively) due to study drug discontinuation.
Patients who discontinue study drug should not be considered withdrawn from the study 
(except if the patient withdraws their informed consent).
See Section 6 for the required assessments of these patients after study drug discontinuation. 
Patients who are discontinued from the study will not be replaced.
5.6.3
Withdrawal of informed consent
Patients may voluntarily withdraw consent to participate in the study for any reason at any 
time.
Withdrawal of consent occurs only when a patient does not want to participate in the study 
anymore, does not want any further visits or assessments, does not want any further study-
related contacts, and does not allow analysis of already obtained biologic material.
If a patient withdraws consent, the Investigator must make every effort (e.g. telephone, e-mail, 
letter) to determine the primary reason for this decision and record this information. The study 
drug must be discontinued and no further assessments or no follow-up visits conducted. All 
biological material that has not been analyzed at the time of withdrawal must not be used. 
Further attempts to contact the patient are not allowed unless safety findings require 
communicating or follow-up.
5.6.4
Loss to follow-up
For patients whose status is unclear because they fail to appear for study visits without stating 
an intention to withdraw, the Investigator should show due diligence by contacting the patient, 
family or family physician as agreed in the informed consent process or later in the study and 
by documenting in the source documents steps taken to contact the patient, e.g. dates of 
telephone calls, registered letters, etc. A patient should not be considered lost to follow-up 
until his/her scheduled end of study visit date has passed. 
5.6.5
Early study termination
The study can be terminated at any time for any reason by Novartis. Should this be necessary, 
the patient should be seen as soon as possible and treated as a discontinued patient as 
described in Section 6. The Investigator may be informed of additional procedures to be 
followed in order to ensure that adequate consideration is given to the protection of the 
patient’s interests. The Investigator will be responsible for informing the Institutional Review 
Boards/Independent Ethics Committees (IRBs/IECs) of the early termination of the study or if 
prior agreed with Novartis, the sponsor or delegates could inform these institutions on behalf 
of the investigational site, if allowed as per local practice.

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6
Visit schedule and assessments
Screening will be flexible in duration and is recommended not to exceed 4 weeks. The 
patients will sign the ICF, be evaluated for eligibility and will have all Screening visit 
assessments done as indicated in Table 6-1.
Table 6-1 lists all of the assessments and indicates with an “X” at which visits the assessments 
are performed. An ‘S’ indicates the data for that assessment are in the source documents at the 
study center. 
If for any reason the patient is a screen failure, the patient may be rescreened. If the reason for 
screen failure is regarded as a transient constraint for study participation then there is no 
restriction on the number of times a potential patient may be rescreened or on how much time 
must pass from the date of screen failure and the date of rescreening. 
IF a patient rescreens for the study, THEN the patient must sign a new ICF and be issued a 
new Patient Number prior to any Screening assessment being conducted for the patient under 
the new Screening Patient Number. For all patients, the Investigator/qualified study center
staff will record if the patient was rescreened on the CRF and any applicable Screening
numbers the patient was issued prior to the current Screening number.
The date of the new informed consent signature must be entered on the appropriate CRF page. 
Informed consent for a screened or rescreened patient must be obtained prior to performing 
any study-related assessment or collecting any data for the Screening Visit. For rescreening, 
all Screening assessments must be performed in accordance with the protocol, except for the 
TB work up, if applicable, if performed not more than 12 weeks prior to Day 1 (Baseline). If 
the date of the TB work-up is less than 12 weeks from Baseline then the TB work-up does not 
have to be repeated; however, the patient must repeat the QFT analyzed by the central 
laboratory. 
During the study, patients may be seen at an unscheduled visit, e.g. if they experience 
deterioration of psoriasis or suspected AEs. During these unscheduled visits, study drug will 
NOT be administered.
Patients should be seen for all visits on the designated day or as closely as possible to the 
original planned visit schedule (recommended visit windows are in Table 6-1) calculated 
starting from Baseline. Every effort should be made to respect the timeframe for all visits. 

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Recommended visit windows
Treatment periods:

± 2 days for Visits 2, 3, 4, 5 and 9 (Baseline, Week 1, 2, 3, 4 and 16) in Treatment 
Period 1; 

± 2 days for all study drug home administrations

± 5 days for all other study visits 

Visit 1 and Visit 2 must not be conducted on the same day and all relevant information for 
Visit 2 must be available before treating the patient. It is recommended that the Screening
period does not exceed 4 weeks.
Patients who discontinue study drug prematurely for any reason (other than withdrawal of 
informed consent) before the end of the main treatment period will enter a 4 weeks post 
treatment follow-up period, unless the patient withdraws his/her informed consent, in which 
case an end-of study visit should be performed, if agreeable by the patient.
If a patient refuses to return for these assessments or is unable to do so, every effort should be 
made to contact them, or a knowledgeable informant, by telephone or by sending appropriate 
correspondence (i.e. certified letter) immediately. At this contact, the safety (e.g. potential 
occurrence of AEs or SAEs) and the primary reason for the patient’s premature withdrawal 
should be determined. As a minimum, these patients will be contacted for safety evaluations 
during the 4 weeks following the last dose of study drug or the 30 days point following the 
last study visit (whichever is later). Documentation of attempts to contact the patient should 
be recorded in the patient source documents.
Possible order of assessments:
Overall, it has been estimated that completion of PROs may take up to a maximum of 
approximately 60 minutes; it is recommended that the PROs might be administered to patients 
in the same sequence at each visit.
Suggested guidelines for conduct of the visit assessments are provided below:

Patient to complete PROs prior to any other study assessments or influence by the study 
site in the following order:

NRS (itching, scaling and pain VAS)

DLQI

EQ-5D©

HAQ©-DI (only for patients with concomitant PsA)

TSQM

PBI

 
 

Investigator/qualified site staff to complete Investigator/qualified site staff assessments.

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Recommended order is:

IGA mod 2011 

PASI and BSA

Physical examination 

All remaining study visit procedures (e.g. laboratory sample collection, vital signs 
measurements) must be completed prior to study drug dosing.

Contact the electronic study system

(Self-)Administration of study drug.

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Table 6-1
Assessment schedule
Treatment Period 1
Treatment Period 2
Period
Scr
EOT1
EOT2
Unsd
Comments
Visit
1
2
3
4
5
6
7
8
9a, b
10
11
12
13
14c
aVisit 9, patients will have the last assessment 
for Treatment Period 1 performed prior to 
administration of study drug. 
bVisit 9 assessments must be completed for 
patients who discontinue study drug 
prematurely during the Treatment Period 1; 
patient should then enter the post treatment 
follow-up period. 
cVisit 14 assessments must be completed for 
patients who discontinue treatment prematurely 
during the Treatment Period 2.
dUnscheduled visit – assessments at discretion 
of the Investigator.
Week
-4 to 
BL
BL
1
2
3
4
8
12
16
20
24
36
48
52
Recommended visit 
window (days)
±2
±2
±2 ±2 ±5 ±5 ±5
±2
±5
±5
±5
±5
±5
Informed consent
X
Demographics
X
Inclusion/exclusion 
criteria
X
X
These assessments are supported by and 
stored within the source documentation. Data 
relating to inclusion/exclusion criteria are 
captured in the corresponding eCRF.
Smoking history
X
Cardiovascular history
X
Psoriasis: medical 
history / previous 
psoriasis therapies
X
Other medical history
X
Prior and concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examination
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
Height
X
X
Weight
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X

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Treatment Period 1
Treatment Period 2
Period
Scr
EOT1
EOT2
Unsd
Comments
Visit
1
2
3
4
5
6
7
8
9a, b
10
11
12
13
14c
aVisit 9, patients will have the last assessment 
for Treatment Period 1 performed prior to 
administration of study drug. 
bVisit 9 assessments must be completed for 
patients who discontinue study drug 
prematurely during the Treatment Period 1; 
patient should then enter the post treatment 
follow-up period. 
cVisit 14 assessments must be completed for 
patients who discontinue treatment prematurely 
during the Treatment Period 2.
dUnscheduled visit – assessments at discretion 
of the Investigator.
Week
-4 to 
BL
BL
1
2
3
4
8
12
16
20
24
36
48
52
Recommended visit 
window (days)
±2
±2
±2 ±2 ±5 ±5 ±5
±2
±5
±5
±5
±5
±5
Waist and hip 
circumference
X
X
X
X
Laboratory sampling: 
safety panel
(clinical chemistry, 
hematology, urine
dipstick)
X
X
X
X
X
X
X
X
X
X
X
Samples will be shipped to the central 
laboratory for analysis.
Urine dipstick to be used locally
Fasting labs: glucose, 
lipid panel, hsCRP, 
HbA1C
X
X
X
X
QuantiFERON® TB-
Gold in-tube test
X
X
Serum pregnancy test
X
X
Only for females of child-bearing potential.
Urine pregnancy test 
(local)
X
X
X
X
X
X
X
In the event of a positive urine pregnancy test, 
study drug must be withheld and a serum 
pregnancy test performed at the same visit. A 
urine pregnancy test is not required for a 
woman who is sterile or who is post-
menopausal.

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Treatment Period 1
Treatment Period 2
Period
Scr
EOT1
EOT2
Unsd
Comments
Visit
1
2
3
4
5
6
7
8
9a, b
10
11
12
13
14c
aVisit 9, patients will have the last assessment 
for Treatment Period 1 performed prior to 
administration of study drug. 
bVisit 9 assessments must be completed for 
patients who discontinue study drug 
prematurely during the Treatment Period 1; 
patient should then enter the post treatment 
follow-up period. 
cVisit 14 assessments must be completed for 
patients who discontinue treatment prematurely 
during the Treatment Period 2.
dUnscheduled visit – assessments at discretion 
of the Investigator.
Week
-4 to 
BL
BL
1
2
3
4
8
12
16
20
24
36
48
52
Recommended visit 
window (days)
±2
±2
±2 ±2 ±5 ±5 ±5
±2
±5
±5
±5
±5
±5
Site assessments:
IGA mod 2011
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BSA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PRO assessments:
NRS (pain, itching 
and scaling VAS)
X
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
EQ-5D©
X
X
X
X
X
X
X
X
X
HAQ©-DI
X
X
X
X
X
X
X
X
X
Only for patients with concomitant PsA..
TSQM
X
X
X
X
X
X
X
X
X
PBI
X
X
X
X
X
X
X
X
X
AE assessment 
(including injection site 
reactions)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Registration, drug 
supply, or completion
Xe
X
X
X
X
X
X
X
X
X
X
X
X
Xf
eRegistration only
fCompletion only

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Treatment Period 1
Treatment Period 2
Period
Scr
EOT1
EOT2
Unsd
Comments
Visit
1
2
3
4
5
6
7
8
9a, b
10
11
12
13
14c
aVisit 9, patients will have the last assessment 
for Treatment Period 1 performed prior to 
administration of study drug. 
bVisit 9 assessments must be completed for 
patients who discontinue study drug 
prematurely during the Treatment Period 1; 
patient should then enter the post treatment 
follow-up period. 
cVisit 14 assessments must be completed for 
patients who discontinue treatment prematurely 
during the Treatment Period 2.
dUnscheduled visit – assessments at discretion 
of the Investigator.
Week
-4 to 
BL
BL
1
2
3
4
8
12
16
20
24
36
48
52
Recommended visit 
window (days)
±2
±2
±2 ±2 ±5 ±5 ±5
±2
±5
±5
±5
±5
±5
Dispense study drug 
X
X
X
X
X
X
X
X
X
Xg
Xg
X
gincluding kits for home administration
Self-administration log
S
S
S
Sh
S
Patients must return the self-
administration log along with all 
dispensed PFS and drug packaging at 
every visit.
hin case of early discontinuation
Complete Screening 
period eCRF
X
Complete end of main 
treatment period eCRF
X
Complete end of 
treatment period eCRF
X
Abbreviations: X = assessment to be recorded on clinical data base; S = assessment to be recorded on source documentation only
AE: adverse event; BL: baseline; BSA: body surface area; eCRF: electronic case report form; DLQI: Dermatology Life Quality Index; EOT: end of 
treatment; EQ-5D©: EuroQOL 5 dimension; 
 HAQ©-DI: Health Assessment Questionnaire Disability Index; IGA Mod 2011: 
Investigator’s Global Assessment Modified 2011; NRS: Numeric Rating Scale; PASI: Psoriasis Area and Severity Index; PBI: Patient Benefit Index; 
TSQM: Treatment Satisfaction Questionnaire for Medication

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The treatment administration schedule is presented in Table 6-2. 
Table 6-2
Overview of study drug administration for Treatment Period 2
Visit 
9
10
11
12
13
14
15
16
17
18
Week
16
20
24
28
32
36
40
44
48
52
Recommended visit 
window (days)
±2
±5
±5
±2
±2
±5
±2
±2
±5
±5
Study drug 
administration 
S
S
S
H
H
S
H
H
S
Abbreviations: H = home administration; S = administration at study center
6.1
Information to be collected on screening failures 
All patients who have signed informed consent but discontinue prior to first intake of study 
drug on Day 1 (Baseline Visit) are considered to be screen failures. If a patient discontinues 
prior to or at Day 1, the reason for screen failure will be entered on the appropriate eCRF page. 
For details on completing the eCRF please refer to the CRF completion guideline. In brief the 
Screening information such as the visit date, information on demography, informed consent, 
and the inclusion/exclusion criteria, must be completed. The AE eCRF should be completed 
for any AEs that occurred during the Screening period. Information on withdrawal of consent 
must be completed if consent is withdrawn during the Screening period. The Death eCRF 
should be completed in the case of death during the Screening period.
For all patients who sign the informed consent and enter into the next period of the study, all 
AEs occurring after the informed consent is signed will be recorded on the AE eCRF page.
At the discretion of Investigators, abnormal test findings if judged clinically significant should 
be recorded after informed consent signature on the AE eCRF page.
6.2
Patient demographics/other baseline characteristics 
All Baseline assessments should be performed prior to first study drug administration. These 
may occur during the Screening period or at the Baseline Visit depending on the assessment 
(Table 6-1). 
6.2.1
Demographics
Patient demographic data to be collected on all patients include: date of birth, sex, race, 
ethnicity, height, weight and child-bearing potential (for females only).
6.2.2
Psoriasis medical history / previous psoriasis therapies
Patient’s disease history will be collected at the Screening Visit. The information to be 
collected and entered as “psoriasis history” and “prior psoriasis therapies” includes the 
following:

Date of first diagnosis of psoriasis prior to the Baseline Visit (by a physician).

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
Previous treatments of psoriasis (including previous use of topical or systemic therapies as
well as phototherapy and/or photochemotherapy) and the reason for discontinuation.

Presence of PsA and the date of first diagnosis (by a physician).
6.2.3
Smoking history
The current and/or previous use of tobacco products will be recorded, as well as the 
approximate consumption per year. Non-smokers will be advised not to start smoking during 
the study.
6.2.4
Co-morbidities – cardiovascular medical history
Any information pertaining to cardiovascular medical history assessed prior to Screening
should be reported as cardiovascular history in the eCRF. Cardiovascular risk factors should
also be recorded. 
6.2.5
Relevant medical history / current medical conditions
Relevant medical history and current medical conditions (not including psoriasis or PsA) 
present prior to signing the ICF will be recorded in the Medical History eCRF. Whenever 
possible, diagnoses and not symptoms will be recorded.
Patients with Crohn’s Disease are eligible for the study but should be followed closely.
Significant findings that are observed after the patient has signed the ICF and that meet the 
definition of an AE must be recorded in the AE summary pages.
6.2.6
Prior and concomitant medications 
Prior medications taken within the 6 months preceding the study Screening Visit (Visit 1), any 
other relevant medication taken before 6 months at the discretion of the Investigator and any 
concomitant medication irrespective of the start date will be captured in the eCRF. 
6.2.7
Determination of tuberculosis status 
Determination of TB status will be required before administration of study drug and should be 
performed as defined by local guidelines. TB status must be determined by medical history, 
signs, symptoms, and TB testing (via the QFT (Section 6.2.7.1)).
Any significant findings will be recorded in the eCRF, as necessary.
6.2.7.1
QuantiFERON TB-Gold In-Tube assay
A QFT will be performed to assess the TB status at Screening for all patients. This test will 
only be used to determine patient’s eligibility for the study. The test will be used to screen the 
patient population for latent TB infection (Doherty et al 2008). 
This blood-based assay is specific for Mycobacterium tuberculosis and is not influenced by 
previous Bacillus Calmette-Guérin vaccination or exposure to other Mycobacteria species. 
This test, in contrast to the purified protein derivative skin test, is also insensitive to a booster 
effect since the patient is not exposed to the vaccine. The assay measures the production of 
interferon-gamma and presents it relative to a negative and a positive control sample (Manuel 

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and Kumar 2008). The QFT will be supplied by the central laboratory. Details on the 
collection, shipment of samples and reporting of results by the central laboratory are provided 
to Investigator/qualified study center staff in the laboratory manual (see Figure 6-1). 

If the test result is negative, the patient may be enrolled

If the test result is positive, the Investigator should perform workup for the test result as 
per local procedures. If a TB workup was conducted prior to Screening the patient, results 
of the workup can be used to assess eligibility provided the workup was conducted within 
12 weeks prior to Baseline. 
o
Patients positive for latent TB per workup may be enrolled in the study if 
sufficient treatment has been initiated according to local routine clinical practice 
and will be maintained for the prescribed duration. Patients positive for active TB 
per workup are not eligible for the study.
o
Patients negative for TB (no signs of latent or active TB) per workup may be 
enrolled in the study.

If the test result is indeterminate, it is recommended to repeat the test once. The 
Investigator may decide to skip the repetition of the test and proceed directly to the 
workup (but this is not recommended). If a TB workup was conducted prior to Screening
the patient, results of the workup can be used to assess eligibility if the workup was 
conducted within 12 weeks prior to Day 1 (Baseline Visit). 
o
If the second test is negative, the patient may be enrolled.
o
If the second test is positive or indeterminate, the Investigator should perform the 
work up as per local guidelines. The patient will not be eligible for enrollment if:
o
“active TB is present “or 
o
if “latent TB is present” and is untreated as per local guidelines. 
Patients negative for TB per workup (no signs of latent or active TB) may be 
enrolled into the study if the workup was conducted within 12 weeks prior to 
Day 1 (Baseline Visit).

If eligibility is being assessed with only 1 test result and a TB workup (i.e. no second TB 
test will be performed), the TB test to assess eligibility must have been done via the 
central laboratory for the study within the Screening period (within 4 weeks prior to Day 1 
[Baseline Visit]) and the TB workup will only be considered if it was completed within 
12 weeks prior to Baseline. Patients who are positive for latent TB per workup may be 
enrolled to the study if sufficient treatment has been initiated according to local routine 
clinical practice and will be maintained for the prescribed duration. Patients positive for 
active TB per workup are not eligible for the study. Patients negative for TB per workup 
(no signs of latent or active TB) may be enrolled in the study.

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Figure 6-1
Tuberculosis screening flowchart
Abbreviations: TB: tuberculosis, QFT: QuantiFERON® TB-Gold In-Tube test
The patient will not be eligible for enrollment if “active TB is present” or if “latent TB is present and is untreated as per local 
guidelines.”
* If the first QuantiFERON® TB-Gold In-Tube test is indeterminate, the Investigator may choose to perform a second test or 
refer the patient for TB workup per local guidelines. 
** If the result of any QuantiFERON® TB-Gold In-Tube test is “positive” or the results of 2 sequential tests are 
“indeterminate,” the patient must be referred to have a TB workup per local guidelines (if no workup within 12 weeks prior to 
enrollment is available). 

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6.2.8
Other Baseline characteristics 
Baseline characteristic data to be collected for all patients includes (all laboratory tests are 
performed centrally except where indicated; see also Table 6-1) the following:

Vital signs, hematology, clinical chemistry, urine, fasting lab tests (glucose, lipid panel, 
HbA1c and hsCRP), physical examination, height, weight, past medical history record 
of HIV, hepatitis B virus, and hepatitis C virus history. A urine pregnancy test will be 
performed for women of child-bearing potential. 

Baseline efficacy assessments of IGA mod 2011, PASI and BSA.

Baseline PRO assessments of DLQI, EQ-5D©, NRS (itching, scaling and pain VAS), 
HAQ©-DI (only for patients with concomitant PsA), TSQM and PBI. 

6.3
Treatment exposure and compliance 
All doses of study drug administration will be recorded in the eCRF. Patient compliance to the 
study drug should be assessed by qualified study center personnel at each study visit using the 
study kits and documentation regarding study drug dispensation and administration.
Compliance will also be assessed continuously during the conduct of the study by Novartis 
study personnel using medication kits and corresponding documentation. Study drug doses 
and corresponding dates of self-administration at home should be documented in a 
self-administration log. Patients are required to return the self-administration log as well as all 
dispensed study drug at every visit back to the study center for a compliance check. 
6.4
Efficacy
All efficacy assessments should be performed prior to administration of the study drug.
6.4.1
Investigator’s global assessment (IGA mod 2011)
The IGA mod 2011 will be conducted for overall psoriatic disease as indicated in the 
assessment schedule in Table 6-1. It is recommended that the same evaluator conducts the 
assessment throughout the study wherever possible. 
The IGA mod 2011 used in this study is static, i.e. it refers exclusively to the patient’s 
disease state at the time of the assessments, and does not attempt a comparison with any of the 
patient’s previous disease states, whether at Baseline or at a previous visit.
The IGA mod 2011 rating scale for overall psoriatic disease is shown in Table 6-3.
Patients require an IGA mod 2011 score at Baseline of 3 or 4 in order to participate in the 
study. Based on this scale, a patient will be considered as an IGA 0 or 1 responder if they 
achieve a score of 0 or 1 and improve by at least 2 points on the IGA scale at a given time 
point compared to their score at Baseline.
The IGA mod 2011 score will be recorded in the eCRF.

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Table 6-3
The IGA mod 2011 rating scale
Score
Short description
Detailed description
0
Clear
No signs of psoriasis. Post-inflammatory hyperpigmentation may be 
present.
1
Almost clear
Normal to pink coloration of lesions; no thickening; no to minimal 
focal scaling.
2
Mild
Pink to light red coloration; just detectable to mild thickening; 
predominantly fine scaling.
3
Moderate
Dull bright red, clearly distinguishable erythema; clearly 
distinguishable to moderate thickening; moderate scaling.
4
Severe
Bright to deep dark red coloration; severe thickening with hard 
edges; severe / coarse scaling covering almost all or all lesions.
Note: Involvement of nails is not part of the assessment
6.4.2
Assessment of psoriasis area and severity index (PASI) and total body 
surface area (BSA)
The Investigator or trained qualified designee will complete the PASI assessment as indicated 
in Table 6-1. Whenever possible, the same evaluator should perform this assessment at all 
visits. The total BSA affected by plaque-type psoriasis will be estimated from the percentages 
of areas affected, including head, trunk, upper limbs and lower limbs (see below for full 
details of the PASI assessment). The following calculations will be done: each reported 
percentage will be multiplied by its respective body region corresponding factor (head = 0.1, 
trunk = 0.3, upper limbs = 0.2, lower limbs = 0.4). The resulting 4 percentages will be added 
to estimate the total BSA affected by plaque-type psoriasis. 
The PASI score (Fredriksson and Pettersson 1978; Weisman et al 2003; Gottlieb et al 2006) 
will be derived as indicated in Table 6-4. The head, trunk, upper limbs and lower limbs are 
assessed separately for erythema, thickening (plaque elevation, induration), and scaling 
(desquamation). The average degree of severity of each sign in each of the 4 body regions is 
assigned a score of 0-4. The area covered by lesions on each body region is estimated as a 
percentage of the total area of that particular body region. Further practical details to help with 
the assessment are provided below:
1. The neck is assessed as part of the head.
2. The axillae and groin are assessed as part of the trunk.
3. The buttocks are assessed as part of the lower limbs.
4. When scoring the severity of erythema, scales should not be removed.
Because the head and neck, upper limbs, trunk and lower limbs correspond to approximately 
10%, 20%, 30% and 40% of the BSA, respectively, the PASI score is calculated using the 
formula:
PASI = 0.1 (EH+IH+DH)AH + 0.2(EU+IU+DU)AU + 0.3(ET+IT+DT)AT + 0.4(EL+IL+DL)AL
The keys for the letters are provided in Table 6-4. 
PASI scores can range from a lower value of 0, corresponding to no signs of psoriasis, up to a 
theoretic maximum of 72.0. The Baseline value for analysis of PASI is collected at Day 1 

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(Baseline Visit). Patients require a total BSA affected by plaque-type psoriasis of ≥ 10% and a 
PASI score of ≥10% at Baseline to be eligible for this study.
Table 6-4
The PASI scoring system
Body 
region
Erythema (E)
Thickening 
(plaque elevation, 
induration, I)
Scaling 
(desquamation, D)
Area score
(based on true 
area %, A)*
Head (H)†
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=no involvement
1=>0-<10%
2=10-<30%
3=30-<50%
4=50-<70%
5=70-<90%
6=90-100%
Trunk (T)‡
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=no involvement
1=>0-<10%
2=10-<30%
3=30-<50%
4=50-<70%
5=70-<90%
6=90-100%
Upper 
limbs (U)
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=no involvement
1=>0-<10%
2=10-<30%
3=30-<50%
4=50-<70%
5=70-<90%
6=90-100%
Lower 
limbs (L)§
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=no involvement
1=>0-<10%
2=10-<30%
3=30-<50%
4=50-<70%
5=70-<90%
6=90-100%
* Percentage (not score) of body region (not whole body) affected will be entered in the eCRF.
† Neck is assessed as part of the Head (H) body region.
‡ Axillae and groin are assessed as part of the Trunk (T) body region.
§ Buttocks are assessed as part of the Lower limbs (L) body region.
6.4.3
Definitions of efficacy variables based on PASI
The following definitions will be used in this study based on the EMA guideline on clinical 
investigation 
of 
medicinal 
products 
indicated 
for 
the 
treatment 
of
psoriasis 
(CHMP/EWP/2454/02 corr):

PASI 50 response (partial response): patients achieving ≥50% improvement 
(reduction) in PASI score compared to Baseline are defined as PASI 50 responders.

PASI 75 response: patients achieving ≥75% improvement (reduction) in PASI score 
compared to Baseline are defined as PASI 75 responders.

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
PASI 90 response: patients achieving ≥90% improvement (reduction) in PASI score 
compared to Baseline are defined as PASI 90 responders.

PASI 100 response / remission: complete clearing of psoriasis (PASI = 0).
6.4.4
Appropriateness of efficacy assessments
All evaluation tools used in this study have been used previously in clinical trials for psoriasis. 
Evaluation of disease severity based on clinical scoring is commonly used in dermatology.
6.5
Safety
From Day 1 (Baseline Visit), all blood draws and safety assessments must be performed as 
indicated in Table 6-1 prior to study drug administration. Appropriate safety assessments (e.g.
evaluation of AEs and SAEs) should be repeated after the dose of study drug is administered. 

Evaluation of all AEs and SAEs including injection site hypersensitivity reactions, vital 
signs, laboratory assessments and occurrence of infections (see Section 7).

Physical examination.

Vital signs.

Height and weight.

Laboratory evaluations (hematology, clinical chemistry, urine dipstick).

Fasting laboratory tests (glucose, lipid profile, HbA1c and hsCRP).

Pregnancy and assessments of fertility.
6.5.1
Physical examination 
A physical examination, including general appearance, will be performed as indicated in 
Table 6-1.
If indicated, based on medical history and/or symptoms, additional examinations will be 
performed at the discretion of the Investigator.
If possible, assessments for an individual patient should be performed by the same member of 
the study center staff throughout the study.
Information for all physical examinations must be included in the source documentation at the 
study center. Significant findings that are present prior to the patient signing informed consent 
must be included in the eCRF. Significant findings made after the signing of the informed 
consent which meet the definition of an AE must be recorded on the eCRF (Section 7).
6.5.2
Vital signs
Vital signs (including blood pressure and pulse measurements) will be assessed as indicated in
Table 6-1. After the patient has been sitting for 5 minutes, with back supported and both feet 
placed on the floor, systolic blood pressure (SBP) and diastolic blood pressure (DBP) will 
be measured twice (1 to 2 minutes apart) using a validated device with an appropriately sized 
cuff (Mancia et al 2007); each BP measurement will be recorded in the source. In case the 
cuff sizes available are not large enough for the patient’s arm, a sphygmomanometer with an 
appropriately sized cuff may be used. 

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If possible, assessments should be performed per patient by the same study center staff 
member throughout the study.
Normal blood pressure will be defined as a SBP of 90 to < 120 mmHg, and a DBP of 60 to 
< 80 mmHg under the measurement conditions outlined above. Notable blood pressure will be 
hypertension (SBP of ≥ 140 mmHg and/or DBP of ≥ 90 mmHg) or hypotension (SBP of 
< 90 mmHg and/or a DBP of < 60 mmHg). A blood pressure indicative of pre-hypertension 
(SBP of 120 to < 140 mmHg and/or DBP of 80 to < 90 mmHg) will not be regarded as 
notable (Chobanian et al 2003).
A normal pulse rate will be defined as a rate of 60 to 100 beats per minute (bpm) under the 
measurement conditions outlined above. Notable pulse rates are a rate below 60 bpm 
(bradycardia) or above 100 bpm (tachycardia).
Whether action needs to be taken to address notable vital signs will be decided by the 
Investigator, taking into account the overall status of the patient. No specific action is foreseen 
as part of the study protocol.
6.5.3
Height, weight, waist and hip circumference
Height and body weight will be measured at the times indicated in Table 6-1. Height and body 
weight will be measured in indoor clothing, but without shoes.
If possible, body weight assessments should be performed by the same study center staff 
member and using the same scale throughout the study. 
Waist and hip circumference will be measured at the times indicated in Table 6-1. According 
to the World Health Organization (WHO) data gathering protocol (STEPwise approach to 
surveillance, 2008), the waist circumference should be measured at the midpoint between the 
lower margin of the last palpable rib and the top of the iliac crest, using a stretch resistant tape 
that provides a constant 100 g tension. Hip circumference should be measured around the 
widest portion of the buttocks, with the tape parallel to the floor.
For both measurements, the individual should stand with feet close together, arms at the side 
and body weight evenly distributed, and should wear little clothing. The patient should be 
relaxed, and the measurements should be taken at the end of a normal expiration. Each 
measurement should be repeated twice; if the measurements are within 1 cm of one another, 
the average should be calculated. If the difference between the 2 measurements exceeds 1 cm, 
the 2 measurements should be repeated.
6.5.4
Laboratory evaluations
Patients should avoid smoking within the hour preceding blood draws.
A central laboratory will be used for analysis of all specimens unless otherwise noted (e.g. 
urine dipsticks will be locally used). Details on the collections, shipment of samples and 
reporting of results by the central laboratory are provided to Investigators in the laboratory 
manual. The laboratory manual should also be consulted for the identification of notable 
values. 

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The Investigator will decide whether action needs to be taken to address notable laboratory 
values, taking into account the overall status of the patient. No specific action is foreseen as 
part of the study protocol.
6.5.4.1
Hematology
Hematology assessments will include hemoglobin, hematocrit, red blood cell (RBC) count, 
WBC count with differential (neutrophils including bands, lymphocytes, monocytes, 
eosinophils, basophils) and platelet count. Hematology assessments will be measured at all 
scheduled study visits within the visit window specified in Table 6-1.
6.5.4.2
Clinical chemistry
Serum chemistry will include urea, creatinine, total bilirubin, alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), gamma glutamyl transferase, and alkaline phosphatase
(ALP). Serum chemistry will be measured at all scheduled study visits within the visit 
window specified in Table 6-1.
6.5.5
Pregnancy and assessments of fertility 
A serum β-hCG test will be performed in all pre-menopausal women as shown in Table 6-1.
All pre-menopausal women who are not sterile at Screening will also have a urine pregnancy 
test performed locally as indicated in Table 6-1.
Any woman with a confirmed positive pregnancy test during Screening is not eligible for 
enrollment.
A positive urine pregnancy test during the treatment periods of the study requires immediate 
interruption of study drug until serum β-hCG is performed and found to be negative. If the 
serum β-hCG test is positive, the study drug must be definitively discontinued, as described in
Section 5.6.2.
6.5.6
Appropriateness of safety measurements
The safety assessments selected are standard for this indication/patient population.
6.6
Other assessments 
Health-related QoL(HR-QoL) assessments should be obtained as shown in Table 6-1.
Assessments can per collected either by using paper forms or with support of an electronic 
system.
6.6.1
Health-related quality of life
The impact of psoriasis on various aspects of a patient’s HR-QoL will be assessed by the 
following validated instruments, each of which will be performed as indicated in Table 6-1:

NRS (itching, scaling and pain VAS)

DLQI


EQ-5D©

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
HAQ©-DI

TSQM

PBI
All these QoL assessments should be completed by the patient 
 
 before they see the study physician (Investigator or designee) who will 
perform the Investigator assessments. All assessments will be completed in the language the 
respondent is most familiar with, at the scheduled visit before the patient sees the Investigator
for clinical assessments. The respondent should be given sufficient space and time to 
complete the questionnaires. The study coordinator should check the questionnaires for 
completeness and encourage the respondent to complete any missing responses. Prior to 
clinical examination, the Investigator should review the completed questionnaires for 
responses that may indicate potential AEs or SAEs. 
If AEs or SAEs are confirmed, the Investigator must record the events as per the instructions 
in Section 7.
Investigators should not encourage respondents to change the responses reported in the 
completed questionnaires.
6.6.1.1
Numeric rating scale: patient’s assessment of pain, itching and 
scaling
A self-administered, 11-point NRS (0-10) will be used to evaluate the patient’s assessment of 
their current pain, itching and scaling. Respondents will answer the following questions for 
the assessment of: 

Pain: Overall, how severe was your psoriasis-related pain over the past 24 hours?

Itching: Overall, how severe was your psoriasis-related itch over the past 24 hours?

Scaling: Overall, how severe was your psoriasis-related scaling over the past 24 hours?
Patients have to rate their pain, itching, and scaling from 0 to 10 (11-point scale), with the 
understanding that 0 represents the absence or null end of the pain, itching, or scale intensity 
(i.e. no pain, itching or scaling) and 10 represents the other extreme of pain, itching, or scaling 
intensity (i.e. pain, itching or scaling as bad as it could be). The number that the patient selects 
represents his or her intensity score.
The NRS scale will be completed by the patient as indicated in Table 6-1.
6.6.1.2
Dermatology life quality index
The DLQI© is a 10-item general dermatology disability index designed to assess HR-QoL in 
adult patients with skin diseases such as eczema, psoriasis, acne, and viral warts (Finlay and 
Khan 1994; Basra et al 2008). 
The measure is self-administered and includes domains of daily activities, leisure, personal 
relationships, symptoms and feelings, treatment, and work/school. The measure is widely 
used: it has been tested across 33 different skin conditions and is available in 85 languages. 
The DLQI is the most frequently used instrument in studies of randomized controlled trials in 
dermatology. 

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The recall period is the previous week and the instrument takes 1 to 2 minutes to complete.
Each item has 4 response categories ranging from 0 (not at all) to 3 (very much). “Not 
relevant” is also a valid response and is scored as 0. The DLQI© total score is a sum of the 
10 questions. Scores range from 0 to 30, with higher scores indicating greater health-related 
QoL impairment. Each subscale of the DLQI© may also be analyzed separately.
The DLQI questionnaire will be completed by the patient as indicated in Table 6-1.
6.6.1.4
EuroQOL 5-Dimension Health Questionnaire
The EQ-5D© is a generic instrument developed by the EuroQoL group to assess patients’ 
health status for clinical and economic appraisal, which was introduced in 1990 (The EuroQol 
Group 1990). Available in over 100 official language versions, it provides a simple 
descriptive profile and a single index value for health status. The recall period is “today”, and 
the instrument takes 1 to 2 minutes to complete. The instrument essentially consists of 2 
pages; the EQ-5D© descriptive system and the EQ-5D© VAS. The EQ-5D© descriptive system 
comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort 

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and anxiety/depression. Each dimension has 5 response levels: no problems, slight problems, 
moderate problems, severe problems and unable. The patient is asked to indicate the patient’s 
health state by ticking (or placing a cross) in the box against the most appropriate statement in 
each of the 5 dimensions. 
A unique health state is defined by combining 1 level from each of the 5 dimensions. Health 
states may be converted into a single number, called weighted index, by applying values (also 
called weights) to each of the levels in each dimension (Dolan 1997). The weighted index 
constitutes a measure of utility. The VAS records the respondent’s self-rated health on a 
vertical 20-cm VAS where the endpoints are labelled “best imaginable health state” and 
“worst imaginable health state.” This information can be used as a quantitative measure of 
health outcome as judged by the individual respondents.
The EQ-5D© questionnaire will be completed by the patient as indicated in Table 6-1.
6.6.1.5
Health assessment questionnaire – disability index (subjects with PsA 
only)
The Health Assessment Questionnaire (HAQ©) was developed by Stanford University and is 
one of the most widely used measures to assess the long-term influence of chronic disease on 
a patient’s level of functional ability and activity restriction. Although originally developed 
for use in subjects with rheumatic disease, the HAQ© has been employed across a large 
variety of disease areas. The disability assessment component of the HAQ©, the HAQ©-DI 
(Health Assessment Questionnaire – Disability Index) assesses a patient’s level of functional 
ability and includes questions on fine movements of the upper extremity, locomotor activities 
of the lower extremity, and activities that involve both upper and lower extremities. There are 
20 items in 8 categories of functioning including dressing and grooming, arising, eating, 
walking, hygiene, reach, grip, and usual activities. The stem of each item asks over the past 
week “Are you able to...” perform a particular task. Each item is scored on a 4-point scale 
from 0 to 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2), 
and unable to do (3). The HAQ©-DI also includes questions about the use of ‘aids or devices’ 
and aid from other people to supplement the answers given to the 20 items.
The purpose of the HAQ©-DI in this study is to assess the functional ability of subjects with 
PsA.
The questionnaire will be completed by the subject as specified in Table 6-1 by all patients 
with a medical history of PsA recorded in the eCRF during the Screening period.
6.6.1.6
Treatment satisfaction questionnaire for medication
The 14-item TSQM (TSQM Version 1.4) is a reliable and valid instrument to assess patient 
satisfaction with medication, providing scores on 4 scales; side effects (3 items), effectiveness 
(5 items), convenience (3 items) and global satisfaction (3 items). In naturalistic studies, 
administering the TSQM with the side effects domain could provoke the physician to assess 
the presence or absence of AEs in a way that is clinically atypical, carrying the potential to
interfere with routine medical care. As a result, an abbreviated 9-item TSQM (TSQM-9), 
derived from the TSQM Version 1.4 but without the 5 items of the side effects domain was 
created. The TSQM-9 provides a suitable measure of treatment satisfaction with medication in 

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studies where measuring patient-reported side effects has a potential to interfere with the 
study objectives. This abbreviated TSQM will be used in this study (Bharmal et al 2009) as
specified in Table 6-1. 
6.6.1.7
Patient benefit index
The PBI is based on questioning the patient about the importance of individual therapy needs 
from a standardized list prior to treatment and presenting these items again during or after 
completion of the treatment, with the patient being asked to rate the extent to which the 
previous objectives were achieved through treatment (Augustin et al 2009). The achieved 
benefits according to the individual needs can finally be weighted. The PBI was developed 
and validated for skin diseases in general (Augustin et al 2009), but a range of disease specific 
PBI versions has been developed, including psoriasis (Feuerhahn et al 2012).
The questionnaire includes 23 items on patient-relevant therapy needs and benefits. The first 
part of the instrument, the ‘Patient Needs Questionnaire’ (PNQ), is filled in by the patients 
before therapy. A 5-step Likert scale (0 = ‘not important at all’ to 4 = ‘very important’) 
records the individual relevance of the different items to the patients. The second part, the 
PBQ, is filled in by the patients during or after therapy. It comprises the same items as the 
PNQ, but in contrast, the patients evaluate the extent to which the treatment needs have been 
fulfilled by therapy (scaled from 0 = ‘treatment did not help at all’ to 4 = ‘treatment helped a 
lot’). In addition, the Likert scale contains the option ‘does not apply to me’ in the PNQ and 
the option ‘did not apply to me’ in the PBQ. The needs prior to treatment (PNQ) and the 
benefits achieved by treatment (PBQ) are converted to a weighted index value, the PBI in the 
narrower sense. It can have a value from 0 = ‘no benefit’ to 4 = ‘maximal benefit’. A PBI 
value of C1 is considered as relevant benefit.
The PBI questionnaire will be completed by the patient as indicated in Table 6-1.
6.6.2
Resource utilization
Not applicable.
6.6.3
Pharmacokinetics
Not applicable.
6.6.4
Other biomarkers
If there is the possibility that patients can participate in a biomarker sub-study then eligibility 
criteria and all study details shall be explained in a corresponding separate study protocol.

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7
Safety monitoring 
7.1
Adverse events
An AE is any untoward medical occurrence (i.e. any unfavorable and unintended sign 
(including abnormal laboratory findings), symptom or disease) in a patient or clinical 
investigation patient after providing written informed consent for participation in the study. 
Therefore, an AE may or may not be temporally or causally associated with the use of a
medicinal (investigational) product. Study drug includes the study drug under evaluation and 
the comparator treatment that is given during any phase of the study. Medical 
conditions/diseases present before starting study drug are only considered AEs if they worsen 
after starting the study drug. All patients who have signed informed consent and are entered 
into the next period of the study will have all AEs occurring after informed consent is 
signed recorded on the AE CRF.
The occurrence of AEs should be sought by non-directive questioning of the patient at each 
visit during the study. Adverse events may also be detected when they are volunteered by the 
patient during or between visits or through physical examinations, laboratory tests, or other 
assessments.
Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
following criteria:

they induce clinical signs or symptoms. 

they are considered clinically significant.

they require therapy.
Clinically significant abnormal laboratory values or test results should be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
Baseline or the previous visit, or values which are considered to be non-typical in a patient 
with underlying disease. Investigators have the responsibility for managing the safety of 
individual patient and identifying AEs. Alert ranges for laboratory and other test 
abnormalities are included in Appendix 1.
Adverse events should be recorded in the AE eCRF with the following information:

Severity grade:
o
Mild: usually transient in nature and generally not interfering with normal 
activities.
o
Moderate: sufficiently discomforting to interfere with normal activities.
o
Severe: prevents normal activities.

Relationship of the AE to the study drug(s) (Suspected: Yes or No).

Duration (start and end dates, or if the event is ongoing at the final examination).

Whether it constitutes a SAE.

Action taken with the study drug.

Concomitant medication or therapies taken.

Outcome.

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A SAE is defined as event which: 

Is fatal or life-threatening.

Results in persistent or significant disability/incapacity.

Constitutes a congenital anomaly/birth defect.

Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:
o
Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition.
o
Elective or pre-planned treatment for a pre-existing condition that is unrelated to 
the indication under study and has not worsened since signing the informed 
consent.
o
Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission. 
o
Social reasons and respite care in the absence of any deterioration in the patient’s 
general condition.
Is medically significant, i.e. defined as an event that jeopardizes the patient or may require 
medical or surgical intervention to prevent one of the outcomes listed above. Examples 
include allergic bronchospasm (a serious problem with breathing) requiring treatment in an 
emergency room, serious blood dyscrasias (blood disorders) or seizures/convulsions that do 
not result in hospitalization. The development of drug dependence or drug abuse would also 
be examples of important medical events. All malignant neoplasms will be assessed as serious 
under “medically significant” if other seriousness criteria are not met.
Unlike routine safety assessments, SAEs are monitored continuously and have special 
reporting requirements; see Section 7.2.
All AEs should be treated appropriately. Treatment may include one or more of the following: 
no action taken (i.e. further observation only); study drug temporarily interrupted; study 
drug(s) permanently discontinued; concomitant medication given; non-drug therapy given. 
The action taken to treat the AE should be recorded on the AE eCRF. 
Once an AE is detected, it should be followed until its resolution or until it is judged to be 
permanent, and assessment should be made at each visit (or more frequently, if necessary) of 
any changes in severity, the suspected relationship to study drug, the interventions required to 
treat it, and the outcome.
Information about common side effects already known about the study drug can be found in 
the IB or will be communicated between IB updates in the form of Investigator Notifications. 
This information will be included in the patient informed consent and should be discussed 
with the patient during the study as needed.
The Investigator should also instruct each patient to report any new AE (beyond the protocol 
observation period) that the patient, or the patient’s personal physician, believes might 
reasonably be related to study drug. This information should be recorded in the Investigator’s 
source documents; however, if the AE meets the criteria of an SAE, it must also be reported to 
Novartis.

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7.2
Serious adverse event reporting 
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent and until 30 days after the last study visit must be reported to 
Novartis within 24 hours of learning of its occurrence. Any SAEs experienced after this 
30-day period should only be reported to Novartis if the Investigator suspects a causal 
relationship to study drug. 
Recurrent episodes, complications, or progression of the initial SAE must be reported as
follow-up to the original episode, regardless of when the event occurs. This report must be 
submitted within 24 hours of the Investigator receiving the follow-up information. An SAE 
that is considered completely unrelated to a previously reported one should be reported 
separately as a new event.
Information about all SAEs (either initial or follow-up information) is collected and recorded 
in English on the paper SAE Report Form or the electronic SAE Form within the data capture 
system (where available). The Investigator must assess the relationship to each specific 
component of the study drug (if the study drug consists of several components). 
Serious adverse events (initial and follow-up) that are recorded electronically in the eCRF 
system (if this function is available) should be entered, saved and e-signed within 24 hours of 
awareness of the SAE or changes to an existing SAE. These data will automatically be 
submitted to Novartis Drug Safety & Epidemiology (DS&E) immediately after Investigator
signature or 24 hours after entry, whichever occurs first. 
Follow-up information provided should describe whether the event has resolved or continues, 
if and how it was treated, whether the treatment code was broken or not and whether the 
patient continued or withdrew from study participation. Each re-occurrence, complication, or 
progression of the original event should be reported as a follow-up to that event regardless of 
when it occurs.
If the SAE is not previously documented in the IB or Package Insert (new occurrence) and is 
thought to be related to the study drug a DS&E Department associate may urgently require 
further information from the Investigator for Health Authority reporting. Novartis may need 
to issue an Investigator Notification to inform all Investigators involved in any study with the 
same study drug that this SAE has been reported. Suspected Unexpected Serious Adverse 
Reactions (SUSARs) will be collected and reported to the Competent Authorities and relevant 
ethics committees in accordance with EU Guidance 2011/C 172/01 or as per national 
regulatory requirements in participating countries.
7.3
Pregnancy reporting
To ensure patient safety, each pregnancy occurring while the patient is on study drug must be 
reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should 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.
Pregnancy should be recorded on a Clinical Trial Pregnancy Form and reported by the 
Investigator/qualified study center staff to the local Novartis DS&E Department. Pregnancy 

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follow-up should be recorded on the same form and should include an assessment of the 
possible relationship to the study drug.
Any SAE experienced during pregnancy must be reported on the SAE Report Form.
8
Data review and database management 
8.1
Site monitoring 
Before study initiation, at a study center initiation visit or at an Investigator’s meeting, a 
Novartis representative will review the protocol and eCRFs with the Investigators and their 
staff. During the study, the field monitor will visit the study center regularly to check the 
completeness of patient records, the accuracy of entries in the eCRFs, the adherence to the 
protocol and to GCP, the progress of enrollment, and to ensure that study drug is being stored, 
dispensed, and accounted for as appropriate. Key study personnel must be available to support 
the field monitor during these visits.
In addition, monitoring of treatment accountability will be performed continuously by a field 
monitor during study center visits and at the completion of the study. The field monitor will 
regularly check that study drug is being stored, prepared, dispensed and accounted as 
appropriate. 
The Investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, and the results of any other tests or assessments. All information 
on CRFs must be traceable to these source documents in the patient’s file. The Investigator
must also keep the original ICF signed by the patient (a signed copy is given to the patient).
The Investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the CRF entries. Novartis monitoring standards require full verification 
for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. 
Additional checks of the consistency of the source data with the CRFs are performed 
according to the study-specific monitoring plan. No information in source documents about 
the identity of the patients will be disclosed.
8.2
Data collection 
Designated Investigator staff (at the study centers) will enter the data required by the protocol 
into the eCRF system. Designated Investigator staff will not be given access to the system
until they have been trained. Automatic validation procedures within the system check for 
data discrepancies during and after data entry and (by generating appropriate error messages)
allow the data to be confirmed or corrected online by the designated Investigator study center
staff. The Investigator must certify that the data entered into the eCRFs are complete and 
accurate. After database lock, the Investigator will receive copies of the patient data for 
archiving at the study center. 

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8.3
Database management and quality control 
Novartis staff (or designated contract research organization (CRO) staff) review the data 
entered into the CRFs by Investigator/qualified study center staff for completeness and 
accuracy and instruct the study center personnel to make any required corrections or additions. 
Queries are sent to the study center using an electronic data query. The Investigator/qualified 
study center staff are required to respond to the query and confirm or correct the data. If the 
electronic query system is not used, a paper Data Query Form will be faxed to the study center. 
Study center personnel will complete and sign the faxed copy and fax it back to Novartis staff 
who will make the correction to the database. The signed copy of the Data Query Form is kept 
at the Investigator study center.
Concomitant medications entered into the database will be coded using the WHO Drug 
Reference List, which employs the Anatomical Therapeutic Chemical classification system. 
Concomitant procedures, non-drug therapies and AEs will be coded using the Medical 
dictionary for regulatory activities (MedDRA) terminology.
Laboratory samples will be processed centrally and the results will be sent electronically to 
Novartis (or a designated CRO).
Medical history and AEs will be coded using MedDRA terminology.
Efficacy assessments (IGA mod 2011, PASI and BSA) will be performed using an electronic 
device or paper forms. In case electronic devices are used but there is a data collection failure,
a paper-based process is acceptable and details of the whole process are described in a 
separate user manual.
PROs assessments (DLQI, EQ-5D©, NRS (itching, scaling and pain VAS), HAQ©-DI, TSQM 
and PBI) will be performed using electronic devices or paper forms. In case electronic devices 
are used but there is a data collection failure a paper-based process is acceptable and details of 
the whole process are described in a separate user manual.
 
All efficacy assessments and PRO assessments will be maintained in a central database and in 
case the database is managed by a vendor results will be sent electronically to Novartis (or a 
designated CRO).
Data about all study drug(s) dispensed to the patient and all dosage changes will be tracked 
using an electronic study system. The system will be either supplied by a vendor or Novartis 
directly, who will also manage the database. The database will be sent electronically to 
Novartis (or a designated CRO) in case a vendor is used.
The occurrence of relevant protocol deviations will be determined. After these actions have 
been completed and the database has been declared to be complete and accurate, it will be 
locked and the treatment codes will be made available for data analysis. Any changes to the 
database after that time can only be made after written agreement by Novartis study
management.

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8.4
Data monitoring committee 
In 
alignment 
with 
the 
EMA 
Guideline 
on 
Data 
Monitoring 
Committees 
(EMEA/CHMP/EWP/5872/03 Corr) no Data Monitoring Committee (DMC) is deemed to be 
required for this Phase 4 clinical study. A pharmacovigilance review concluded that 
substantial amount of safety data for the study drugs have been collected through all study 
phases and that a DMC would not be beneficial for the study. 
8.5
Adjudication committee
Not applicable.
9
Data analysis 
Summary statistics for continuous variables will include N, mean, standard deviation, 
minimum, median, maximum. Summary statistics for discrete variables will be presented in 
contingency tables and will include absolute and relative frequencies. 
If not otherwise specified, p-values will be presented as two-sided p-values and 2-sided CIs 
will be displayed.
9.1
Analysis sets
The following analysis sets will be used in the analyses:
Enrolled set: All patients who are enrolled are included in the Enrolled set.
Safety set: The Safety set includes all patients who received at least one dose of study drug. 
Full Analysis set: The Full Analysis set includes all patients who received at least one dose of 
study drug. 
9.2
Patient demographics and other baseline characteristics 
Demographics and other Baseline characteristics will be collected at Screening (Visit 1) or at 
Baseline (Visit 2) prior to first study drug administration for the efficacy and PRO 
measurements. Summary statistics will be provided for demographic and Baseline 
characteristics. Data will be summarized for the overall population as well as for the 3 pre-
defined subpopulations with absolute counts and relative frequencies for categorical variables 
and with mean, standard deviation, minimum, median, and maximum for continuous variables. 
Patient background information (medical history and current medical conditions) will be 
summarized by MedDRA primary SOC and preferred term. Summaries for psoriasis specific 
medical history and cardiovascular medical history will also be provided.
9.3
Treatments 
The analysis of study treatment data will be based on the Safety set.
Duration (days) of exposure to study drug will be summarized. The number of secukinumab 
injections will be presented by visit and cumulatively. 

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Patients who prematurely discontinue the study drug will be listed along with the reason for 
discontinuation. 
Compliance will be calculated in percent as the number of injections administered divided by 
the number of injections scheduled according to the protocol.
9.3.1
Prior and concomitant medications
Prior and concomitant medications will be summarized by prior psoriasis treatment 
subpopulation in separate tables.
Prior medications are defined as treatments taken and stopped prior to first dose of study drug. 
Any medication given at least once between the day of first dose of study drug and the last 
day of study will be a concomitant medication, including those which were started pre-
Baseline and continued into the treatment period or beyond. 
Medications will be presented in alphabetical order, by ATC codes and grouped by 
anatomical main group. Tables will also show the overall number and percentage of patients 
receiving at least one treatment of a particular ATC code and at least one medication in a 
particular anatomical main group.
9.4
Analysis of the primary variable
9.4.1
Variable
The primary analysis variable is the proportion of patients achieving a DLQI 0/1 response at 
Week 16 in 3 pre-defined subpopulations and in the overall study population.
The analysis of the primary variable will be based on the Full Analysis set.
9.4.2
Statistical model, hypothesis, and method of analysis
The primary analysis of this study will be descriptive without any formal group comparisons 
or hypothesis testing. The absolute and relative frequencies of patients achieving a DLQI 0/1 
response at Week 16 will be calculated for the subpopulations defined above as well as for the 
overall study population. For the proportions, (descriptive) 95% CIs will additionally be 
reported.
9.4.3
Handling of missing values/censoring/discontinuations
The last observation carried forward (LOCF) method will be applied to the continuous 
variables of DLQI score, PASI score and IGA mod 2011 score that are missing after Baseline
regardless to the reason for missing data (e.g. premature study discontinuation, missed visit, 
administrative issues). The binary response variables based on DLQI score, PASI score and 
IGA mod 2011 score will be derived from these imputed values, this means that a patient with 
missing values will be counted as a non-responder unless he already achieved the respective 
response criterion at the last available measurement.
Any missing individual items are treated as missing data. Cases for which a weekly score 
cannot be calculated (less than four completed days) will not be included in the analysis. The 
percent of missing and missing patterns for each item will be assessed.

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9.4.4
Sensitivity analyses
No sensitivity analysis will be performed. 
9.5
Analysis of secondary variables
9.5.1
Efficacy variables
All secondary objectives (as defined under Section 2.2) will be analyzed descriptively, 
similarly to the primary endpoint. Relative and absolute frequencies will be presented for 
categorical variables and mean, SD, median, minimum and maximum will be presented for 
continuous variables. 
 
 
 
9.5.2
Safety variables
Analysis of safety data will be based on the Safety set.
Adverse events
The assessment of safety will be based primarily on the frequency of AEs and SAEs. SAEs 
suspected by the Investigators to be related to the prescribed medication will be summarized 
as appropriate. 
The only AEs that will be counted will be treatment-emergent AEs (TEAEs). A TEAE is 
defined as any AE that develops after initiation of the study treatment or any event already 
present that worsens following exposure to the study treatment. This definition is not used by 
the Investigator, but rather is used in the analysis and reporting of clinical trial data. A patient 
with multiple AEs within a body system will only be counted once towards the total of this 
body system.
The incidence of AEs (new or worsened) will be summarized by primary SOC, preferred term, 
severity and relationship to study drug. In addition, the incidence of death, SAEs, and AEs 
leading to discontinuation will be summarized separately by primary SOC and preferred term.
All AEs will be displayed by group and patient.
Vital signs
All vital signs (including height and weight) will be summarized by prior psoriasis treatment 
group and visit and listed by group, patient and time. Analysis of the vital sign measurements 
using summary statistics for the change from Baseline for each post-Baseline visit will be 
performed.

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Clinical laboratory evaluations
The summary of laboratory evaluations will be presented for the hematology, clinical 
chemistry, and fasting laboratory tests. Descriptive summary statistics for the change from 
Baseline to each visit will be presented. These descriptive summaries will be presented by 
laboratory test and prior psoriasis treatment group. Changes from Baseline will only be 
summarized for patients with both Baseline and post Baseline data.
Shift tables will be provided for all parameters to compare a patient’s Baseline laboratory 
evaluation relative to the most extreme observed value during the treatment phase. For the 
shift tables, the normal laboratory ranges will be used to evaluate whether a particular 
laboratory test value was normal, low, or high for each visit value relative to whether or not 
the Baseline value was normal, low, or high. These summaries will be presented by laboratory 
test and treatment group. Shifts will be presented by visit as well as for most extreme values 
post-Baseline.
Physical examinations
All physical examination data will be listed by prior psoriasis treatment group, patient and 
visit and summary statistics will be provided by prior psoriasis treatment group and visit.
Pregnancy tests
Serum and urine pregnancy tests where applicable will be summarized and listed.
9.5.3
Health-related quality of life
The analysis of the HR-QoL assessments in Section 6.6.1 is described in the SAP.
9.5.4
Resource utilization 
Not applicable.
9.5.5
Pharmacokinetics
Not applicable.
9.5.6
Pharmacogenetics/pharmacogenomics
Not applicable.
9.5.7
Biomarkers
If a biomarker sub study is performed, details will be described in a separate study protocol.
9.5.8
PK/PD
Not applicable.

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9.6
Interim analyses 
An interim analysis describing the self-reported Baseline characteristics and HR-QoL of 
patients prior to treatment may be performed for this study after LPFT. Details will be 
described in the Statistical Analysis Plan (SAP). 
9.7
Sample size calculation
The study aims to estimate primarily the effect of 16 weeks treatment with secukinumab 
300 mg on the QoL of the overall study population as well as within the 3 pre-defined 
subpopulations. It is expected that 40% of the overall study population will fulfil the criteria 
for the definition of subpopulation A; 40% will fulfil the criteria for subpopulation B; and 
20% will fulfil the criteria for subpopulation C.
The DLQI 0/1 response rate in the overall population treated with secukinumab 300 mg s.c. is 
expected to be around 70% at Week 16; however, it may vary within those pre-defined 
subpopulations. A total of 323 patients are required to estimate the response rate of DLQI 0/1 
with a precision (= 95% CI) of 5% if the true response rate is about 70% in the smallest 
subpopulation. To ensure that this precision is achieved in the 3 subpopulations (defined in 
Section 3.1), which consist of 20% to 40% of the overall study population, 1 615 patients in 
total should be recruited into this trial.
10
Ethical considerations 
10.1
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented and reported in accordance with 
the ICH GCP, with applicable local regulations (including European Directive 2001/20/EC, 
and with the ethical principles laid down in the Declaration of Helsinki.
10.2
Informed consent procedures 
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent, or, if incapable of doing 
so, after such consent has been provided by a legally acceptable representative of the patient. 
In cases where the patient’s representative gives consent, the patient should be informed about 
the study to the extent possible given his/her understanding. If the patient is capable of doing 
so, he/she should indicate assent by personally signing and dating the written informed 
consent document or a separate assent form. Informed consent must be obtained before 
conducting any study-specific procedures (i.e. all of the procedures described in the protocol). 
The process of obtaining informed consent should be documented in the patient source 
documents. 
Novartis will provide to Investigators in a separate document a proposed ICF that complies 
with the ICH GCP guideline and regulatory requirements and is considered appropriate for 
this study. Any changes to the proposed consent form suggested by the Investigator must be 
agreed to by Novartis before submission to the IRB/IEC, and a copy of the approved version 
must be provided to the Novartis monitor after IRB/IEC approval.

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Women of child bearing potential should be informed that taking the study drug may involve 
unknown risks to the fetus if pregnancy were to occur during the study and agree that in order 
to participate in the study they must adhere to the contraception requirement for the duration 
of the study. If there is any question that the patient will not reliably comply, they should not 
be entered in the study.
 
10.3
Responsibilities of the investigator/qualified site staff and 
IRB/IEC 
Before initiating a study, the Investigator/institution should obtain approval/favorable opinion 
from the IRB/IEC for the study protocol, written ICF, consent form updates, patient 
recruitment procedures (e.g. advertisements) and any other written information to be provided 
to patients. Prior to study start, the Investigator is required to sign a protocol signature page 
confirming his/her agreement to conduct the study in accordance with these documents and all 
of the instructions and procedures found in this protocol and to give access to all relevant data 
and records to Novartis monitors, auditors, Novartis Clinical Quality Assurance 
representatives, designated agents of Novartis, IRBs/IECs, and regulatory authorities as 
required. If an inspection of the study center is requested by a regulatory authority, the 
Investigator must inform Novartis immediately that this request has been made.
10.4
Publication of study protocol and results 
Novartis assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov. In addition, upon study completion and 
finalization of the study report the results of this study will be either submitted for publication 
and/or posted in a publicly accessible database of clinical study results.
11
Protocol adherence
This protocol defines the study objectives, the study procedures and the data to be collected 
on study participants. Additional assessments required to ensure safety of patients should be 
administered as deemed necessary on a case by case basis. Under no circumstances should an 
Investigator collect additional data or conduct any additional procedures for any research 
related purpose involving any study drugs.
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
Investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC, it cannot be implemented. All significant protocol deviations 
will be recorded and reported in the Clinical Study Report.
11.1
Protocol amendments
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 

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implementation. Only amendments that are intended to eliminate an apparent immediate 
hazard to patients may be implemented immediately provided the health authorities are 
subsequently notified by protocol amendment and the reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the Investigator is 
expected to take any immediate action required for the safety of any patient included in this 
study, even if this action represents a deviation from the protocol. In such cases, the reporting 
requirements identified in Section 7 Safety Monitoring must be followed.
12
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13
Appendix 1: Clinically notable laboratory values and vital 
signs
The following criteria will be used to define expanded limits and notable abnormalities of key 
laboratory tests. Notable values for blood pressure and pulse are presented in Section 6.5.2.
No specific action is pre-defined within this protocol to respond to specific abnormal 
laboratory values, as it will be decided by the Investigator/qualified site staff whether and 
which specific action needs to be taken to respond to any abnormal values, taking into account 
the overall status of the patient. For additional information please refer to the lab manual. 
Liver function and related variables 
ALT (SGPT):
> 3 x upper limit of normal (ULN)
AST (SGOT):
> 3 x ULN
Total bilirubin:
> 1.5 x ULN
Alkaline phosphatase:
> 2 x ULN
Renal function and electrolyte variables
Creatinine (serum):
> 1.5 x ULN
Hematology variables
Hemoglobin:
≥ 20 g/dL decrease from Baseline
Platelet count:
< lower limit of normal (LLN)
White blood cell count:
< 0.8 x LLN
Neutrophils:
< 0.9 x LLN
Eosinophils:
> 1.1 x ULN
Lymphocytes:
> 1.1 x ULN
Urinalysis variable
Protein urine dipstick: 
++* (* ++ is ≥100 mg/dL)