Long Term Clear Skin Maintenance Treatment Optimization in Patients With Moderate to Severe Chronic Plaque Psoriasis: A Randomized, Multicenter, Open-label With Blinded-assessment, Comparative, 52 Week Study to Evaluate the Efficacy, Safety and Tolerability of Secukinumab 300 mg s.c.
Phase: PHASE3
Conditions: Plaque Psoriasis
Sponsor: Novartis Pharmaceuticals

Clinical Development – Medical Affairs Region Europe 
[Cosentyx® (Secukinumab)]
Clinical Trial Protocol 
[CAIN457A3302] / NCT02409667
OPTIMISE (OPtimization of Treatment In MaIntenance with 
SEcukinumab 300 mg)
[Long term clear skin maintenance treatment optimization in 
patients with moderate to severe chronic plaque psoriasis: A 
randomized, multicenter, open-label with blinded-assessment, 
comparative, 52 week study to evaluate the efficacy, safety and 
tolerability of secukinumab 300 mg s.c.]
Authors:
 
Document type:
Amended Protocol Version (Clean)
EUDRACT number:
2014-005339-15
Version number:
v01
Development phase:
Phase 3b
Release date:
16-Jun-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.................................................................................................................9
Amendment rationale ........................................................................................................10
Protocol summary..............................................................................................................12
1
Introduction .......................................................................................................................19
1.1
Background............................................................................................................19
1.2
Purpose ..................................................................................................................20
2
Study objectives.................................................................................................................20
2.1
Primary objective...................................................................................................20
2.2
Secondary objectives .............................................................................................20
2.3
Exploratory objectives...........................................................................................21
3
Investigational plan ...........................................................................................................21
3.1
Study design...........................................................................................................21
3.2
Rationale of study design.......................................................................................24
3.3
Rationale of dose/regimen, route of administration and duration of treatment.....25
3.4
Rationale for choice of comparator .......................................................................26
3.5
Purpose and timing of interim analyses/design adaptations..................................27
3.6
Risks and benefits..................................................................................................27
4
Population..........................................................................................................................28
4.1
Inclusion criteria ....................................................................................................28
4.2
Exclusion criteria...................................................................................................29
5
Treatment...........................................................................................................................31
5.1
Protocol requested treatment .................................................................................31
5.1.1
Investigational treatment.......................................................................31
5.1.2
Additional study treatment....................................................................31
5.2
Treatment groups...................................................................................................31
5.3
Treatment assignment, randomization...................................................................32
5.3.1
IRT Stratification ..................................................................................33
5.4
Treatment blinding.................................................................................................33
5.5
Treating the patient................................................................................................34
5.5.1
Patient numbering .................................................................................34
5.5.2
Dispensing the investigational treatment ..............................................34
5.5.3
Handling of study drug..........................................................................35
 

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5.5.4
Instructions for prescribing and taking study drug ...............................36
5.5.5
Permitted dose adjustments and interruptions of study drug ................37
5.5.6
Rescue medication ................................................................................37
5.5.7
Concomitant treatment..........................................................................37
5.5.8
Prohibited Treatment.............................................................................39
5.5.9
Exposure to light ...................................................................................41
5.5.10
Discontinuation of study drug...............................................................41
5.5.11
Discontinuation from a treatment-free period.......................................42
5.5.12
Withdrawal of consent ..........................................................................42
5.5.13
Loss to follow-up ..................................................................................42
5.5.14
Emergency breaking of assigned treatment code..................................43
5.5.15
Study completion and post-study drug..................................................43
5.5.16
Early study termination.........................................................................43
6
Visit schedule and assessments .........................................................................................43
6.1
Information to be collected on screening failures..................................................51
6.2
Patient demographics/other baseline characteristics .............................................51
6.2.1
Demographics .......................................................................................51
6.2.2
Psoriasis medical history / previous psoriasis therapies .......................51
6.2.3
Smoking history ....................................................................................52
6.2.4
Co-morbidities – cardiovascular medical history .................................52
6.2.5
Relevant medical history / current medical conditions.........................52
6.2.6
Prior and concomitant medications.......................................................52
6.2.7
Determination of tuberculosis status.....................................................52
6.2.8
Other baseline characteristics................................................................55
6.3
Treatment exposure and compliance .....................................................................55
6.4
Efficacy..................................................................................................................55
6.4.1
Investigator’s Global Assessment Modified 2011................................56
6.4.2
Assessment of total body surface area and psoriasis area and 
severity index ........................................................................................56
6.4.3
Definitions of efficacy variables based on psoriasis area and 
severity index ........................................................................................59
6.4.4
Appropriateness of efficacy assessments..............................................59
6.5
Safety.....................................................................................................................59
6.5.1
Physical examination ............................................................................60
6.5.2
Vital signs..............................................................................................60
6.5.3
Height and weight .................................................................................61
6.5.4
Laboratory evaluations..........................................................................61
6.5.5
Electrocardiogram.................................................................................61
 

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6.5.6
Pregnancy and assessments of fertility .................................................62
6.5.7
Appropriateness of safety measurements..............................................62
6.6
Other assessments..................................................................................................62
6.6.1
Resource utilization...............................................................................62
6.6.2
Health-related Quality of Life...............................................................62
6.6.3
Pharmacokinetics ..................................................................................64
6.6.4
Other biomarkers...................................................................................65
7
Safety monitoring..............................................................................................................65
7.1
Adverse events.......................................................................................................65
7.2
Serious adverse events...........................................................................................67
7.2.1
Definition of SAE .................................................................................67
7.2.2
Serious adverse event reporting ............................................................67
7.3
Liver safety monitoring .........................................................................................68
7.4
Pregnancy reporting...............................................................................................69
8
Data review and database management.............................................................................69
8.1
Site monitoring ......................................................................................................69
8.2
Data collection.......................................................................................................70
8.3
Database management and quality control............................................................70
8.4
Data Monitoring Committee..................................................................................71
8.5
Adjudication Committee........................................................................................71
9
Data analysis......................................................................................................................71
9.1
Analysis sets ..........................................................................................................72
9.2
Patient demographics and other baseline characteristics.......................................72
9.2.1
Medical history......................................................................................73
9.3
Treatments .............................................................................................................73
9.3.1
Prior and concomitant treatment............................................................................73
9.4
Analysis of the primary variable............................................................................73
9.4.1
Variable.................................................................................................73
9.4.2
Statistical model, hypothesis, and method of analysis..........................73
9.4.3
Choice of the non-inferiority margin ....................................................74
9.4.4
Handling of missing values/censoring/discontinuations.......................74
9.4.5
Supportive analyses...............................................................................74
9.5
Analysis of secondary variables ............................................................................75
9.5.1
Efficacy variables..................................................................................75
9.5.2
Safety variables .....................................................................................75
9.5.3
Resource utilization...............................................................................76
9.5.4
Pharmacokinetics ..................................................................................76
 

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9.5.5
Pharmacogenetics/pharmacogenomics .................................................76
9.5.6
Biomarkers............................................................................................76
9.6
Interim analyses.....................................................................................................76
9.7
Sample size calculation..........................................................................................77
9.7.1
Power for the key secondary objective .................................................77
10 Ethical considerations........................................................................................................78
10.1
Regulatory and ethical compliance........................................................................78
10.2
Informed consent procedures.................................................................................78
10.3
Responsibilities of the Investigator and IRB/IEC .................................................78
10.4
Publication of study protocol and results...............................................................79
11 Protocol adherence ............................................................................................................79
11.1
Protocol Amendments ...........................................................................................79
12 References .........................................................................................................................80
13 Appendix 1: Clinically notable laboratory values and vital signs.....................................83
14 Appendix 2: Liver event and laboratory trigger definitions and follow-up 
requirements ......................................................................................................................84
List of tables
Table 5-1
Timing of study drug administration by study group............................36
Table 5-2
Prohibited treatment..............................................................................40
Table 6-1
Assessment schedule.............................................................................46
Table 6-2
Overview of study drug administration for Treatment Period 2...........50
Table 6-3
Investigator global assessment modified 2011 rating scale ..................56
Table 6-4
Psoriasis area and severity index scoring system..................................58
Table 14-1
Liver event definitions ..........................................................................84
Table 14-2
Liver event follow-up requirements......................................................85
List of figures
Figure 3-1
Study design..........................................................................................23
Figure 6-1
Tuberculosis screening flowchart .........................................................54
 

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List of abbreviations
AE
Adverse Event
AIN457
Secukinumab
ALT (SGPT)
Alanine Aminotransferase
AST (SGOT)
Aspartate Aminotransferase
bpm
Beats per Minute
BSA
Body Surface Area
CHMP
Committee for Medicinal Products for Human Use
CI
Confidence Interval
CRO
Contract Research Organization
CSR
Clinical Study Report
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Committee
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EMA
European Medicines Agency
EOT
End of Treatment 
EOT1
End of Treatment Period 1
EOT2
End of Treatment Period 2
EQ-5D
Health Status Questionnaire (EuroQOL 5-Dimension Health 
Questionnaire, EQ-5D©)
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GGT
Gamma Glutamyl Transferase
H
Head [PASI scoring system]
hCG
Human Chorionic Gonadotropin
HIV
Human Immunodeficiency Virus
HRQoL
Health-Related Quality of Life
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Conference on Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for Human Use
 

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IEC
Independent Ethics Committee
IGA mod 2011
Novartis Investigator’s Global Assessment modified 2011
IgG
Immunoglobulin G
IL
Interleukin
IUD
Intrauterine Device
IUS
Intrauterine System
IRB
Institutional Review Board
IRT
Interactive Response Technology
L
Lower limbs [PASI scoring system]
LFT
Liver Function Test
MedDRA
Medical Dictionary for Regulatory Activities
NR
Non Responder
NRS
Numeric Rating Scale
NYHA
New York Heart Association 
PASI
Psoriasis Area and Severity Index
PFS
Pre-Filled Syringe
PR
Partial Responder
PRO
Patient Reported Outcomes
RAN
Retreatment as Needed
SAE
Serious Adverse Event
s.c.
Subcutaneous, subcutaneously
SGOT
Serum Glutamic Oxaloacetic Transaminase
SGPT
Serum Glutamic Pyruvic Transaminase
SOC
System Organ Class
SUSAR
Suspected Unexpected Serious Adverse Reaction
T
Trunk [PASI scoring system]
TB
Tuberculosis
TCS
Topical Corticosteroid
TNF
Tumor Necrosis Factor
U
Upper limbs [PASI scoring system]
UNL
Upper Normal Limit
UV
Ultraviolet
WBC
White Blood Cells
 

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WPAI-PSO
Work Productivity and Activity Impairment Questionnaire-Psoriasis
 

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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 study drug package in 
studies that dispense medication using an Interactive Response 
Technology (IRT) system.
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 is followed for progression and/or survival.
Randomization number
A unique identifier assigned to each randomized patient, 
corresponding to a specific treatment group assignment.
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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Amendment rationale 
The main purpose of this Amendment is to align the requirements for the duration of 
contraception to be used by patients during the study with the approved European Summary 
of Product Characteristics. According to the Exclusion criteria (Section 4.2) of the study 
protocol women of childbearing potential must use effective methods of contraception during 
dosing of study treatment and for 16 weeks after stopping treatment, in line with phase III 
AIN457A program study protocols. 
Therefore the advice to female patients to prevent pregnancy is amended to cover also the 
contraception length post treatment requirements of the European Summary of Product 
Characteristics (20 weeks).
In addition, the approved European Summary of Product Characteristics specifies for the pre-
filled secukinumab syringe a warning and precaution for use in case a latex sensitivity would 
be pertinent for a patient. The removable needle cap of the pre-filled syringe 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 pre-filled syringes in latex sensitive 
individuals has not been studied and there is therefore a potential risk of hypersensitivity 
reactions which cannot be completely ruled out. The Exclusion criteria (Section 4.2) of the 
study protocol have been updated accordingly, as well as the Risks and benefits (Section 3.6).
Other sections have been updated to provide clarity.
Changes to the protocol
The main changes made to the protocol are:

Protocol synopsis: updated to reflect the changes in the main protocol text

Section 4.2 exclusion criterion 3 and the Risks and benefits (Section 3.6) are revised 
to include also latex hypersensitivity

Section 4.2 exclusion criterion 8 is revised to align post treatment contraception 
length with the EU Summary of Product Characteristics

Section 6 updated content, incl. Table 6-1, to clarify details for the laboratory 
assessments, clarify that the 5 response level EQ-5D Health Status Questionnaire is 
used, and that Chest X-ray (or CT/MRI) is recorded on source documentation

Section 6.2.5 is updated to include a statement on Crohn’s disease
The first patient was recruited in the study on 12 June 2015 and around 11 of 1580 planned 
patients have been treated with study medication during finalization of the protocol 
amendment.
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red underlined for insertions.
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities.
The changes described in this amended protocol require IRB/IEC approval prior to 
implementation. 
 

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The changes herein affect the Informed Consent. Sites are required to update and submit for 
approval a revised Informed Consent that takes into account the changes described in this 
protocol amendment.
 

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Protocol summary
Protocol number
CAIN457A3302
Title
Long term clear skin maintenance treatment optimization in patients with 
moderate to severe chronic plaque psoriasis: A randomized, multicenter,
open-label with blinded-assessment, comparative, 52 week study to 
evaluate the efficacy, safety and tolerability of secukinumab 300 mg s.c.
Brief title
Efficacy, safety and tolerability assessment of secukinumab 300 mg s.c.
optimization in patients with moderate to severe chronic plaque psoriasis.
Sponsor and clinical 
phase
Novartis; Phase 3b
Investigation type
Drug
Study type
Interventional
Purpose and rationale
Reducing maintenance dosing regimens for patients treated with 
(biologic) drugs offers benefits, such as minimizing patients’ exposure to 
the drug substance while keeping an acceptable clinical response. In 
contrast, patients not responding adequately to a drug substance can 
benefit from an increased frequency of drug dosing. In daily clinical 
practice, a change of the dose frequency for marketed substances can be 
assumed to happen often depending on the treatment response of 
patients. A secukinumab dose of 300 mg s.c. every 4 weeks as a
maintenance treatment dose regimen has been evaluated extensively in 
a Phase 3 clinical trial program and shown strong sustainability of 
treatment response over 52 weeks.
This study will assess if a more prolonged dose interval (every 6 weeks 
compared to every 4 weeks) will allow psoriasis patients who achieve 
clear or almost clear skin after 24 weeks of secukinumab treatment -
Psoriasis Area and Severity Index (PASI) ≥90 - to maintain this skin 
response for a further 28 weeks (52 weeks in total). The study will also 
assess if a dose interval (dosing every 2 weeks compared to every 
4 weeks) will allow psoriasis patients who fail to achieve a PASI 90 
response after 24 weeks of secukinumab treatment to meet the PASI 90 
response target in a further 28-week study period. 
Primary Objective 
The primary objective is to demonstrate in the patient pool of PASI 90 
responders at Week 24 that secukinumab 300 mg s.c. every 6 weeks 
treatment is non-inferior to secukinumab 300 mg s.c. every 4 weeks 
treatment with respect to maintaining a PASI 90 response rate at 
Week 52.
Secondary Objectives
The key secondary objective is to demonstrate in the patient pool of 
PASI 75 responders who do not reach a PASI 90 response at Week 24 
that secukinumab 300 mg s.c. administered every 2 weeks is superior to 
secukinumab 300 mg s.c. administered every 4 weeks at Week 52 based 
on the PASI 90 response rate.
Other secondary objectives are as follows: 
 

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
Evaluate the proportion of PASI 50, PASI 75, PASI 100 and Novartis 
Investigator’s Global Assessment modified 2011 (IGA mod 2011) 0/1 
responder rates at Week 52.

Evaluate the course of mean PASI over time from Week 24 to 
Week 52.

Evaluate the effect of different maintenance treatment frequencies on 
patient reported outcomes (PROs): Dermatology Life Quality Index 
(DLQI©), EuroQOL 5-Dimension Health Questionnaire (EQ-5D©), 
Work Productivity and Activity Impairment Questionnaire-Psoriasis
(WPAI-PSO), and the patient’s assessment of pain, itching and 
scaling.
Exploratory objectives
Exploratory objectives are as follows:

Evaluate the proportion of PASI 50, PASI 75, PASI 90, PASI 100 and 
IGA mod 2011 0/1 responders at Week 24.

Evaluate the time to achieve clear or almost clear skin based on 
PASI 90 when receiving secukinumab 300 mg s.c. every 2 weeks 
compared to every 4 weeks from Week 24 to Week 52.

Evaluate time to first loss of PASI 75 response when receiving 
secukinumab every 2 weeks compared to every 4 weeks from 
Week 24 until Week 52.

Evaluate the safety and tolerability of different maintenance treatment 
regimens of secukinumab 300 mg s.c.

Explore the correlation between the pharmacokinetic (PK) data and 
efficacy outcomes.
Other exploratory objectives for patients with PASI 90 response at 
Week 24 are as follows:

Assess the time to loss of PASI 90 response.

Assess the time to loss of IGA mod 2011 0/1 response.
Study design
This is a randomized, open-label, assessment-blinded, multicenter, 
52-week study to evaluate the efficacy (based on PASI 90), safety and 
tolerability of secukinumab 300 mg s.c. in patients with moderate to 
severe chronic plaque psoriasis. This study consists of 2 treatment 
periods: a 24-week run-in treatment period (Baseline to Week 24) and a 
28-week maintenance treatment period (Week 24 to Week 52). 
For Treatment Period 1 (Baseline to Week 24) all patients will receive the 
same treatment: 300 mg of secukinumab by s.c. injection with initial 
dosing at Weeks 0, 1, 2, and 3 followed by dosing every 4 weeks.
For Treatment Period 2 (Week 24 to Week 52) patients will be randomly 
assigned to one of 4 treatment groups depending on their PASI response 
to treatment. 
Patients with PASI 90 (psoriasis clear or almost clear skin) will be 
randomized at Week 24 on a 1:1 basis to Group 1 or Group 2:

Group 1 (recommended maintenance treatment): secukinumab 
300 mg s.c. every 4 weeks.

Group 2 (experimental dosing maintenance treatment): 
secukinumab 300 mg s.c. every 6 weeks.
Patients who do not achieve a PASI 90 response at Week 24 but achieve 
at least a PASI 75 response will be eligible for dose frequency 
intensification and will be randomized on a 1:1 basis to either Group 3 or 
Group 4:
 

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
Group 3 (recommended maintenance treatment): secukinumab 
s.c. 300 mg every 4 weeks.

Group 4 (experimental maintenance treatment): secukinumab 
s.c. 300 mg every 2 weeks.
Patients from Group 3 and Group 4 will enter a treatment-free follow-up 
period from Week 52 until Week 60.
Patients without a PASI 75 response at Week 24 will not be eligible for 
randomization and will be discontinued from the study. 
Randomization will be stratified by body weight collected at the 
Randomization Visit (< 90 kg or ≥90 kg). 
Population
The study population will consist of a representative group of male and 
female patients (≥ 18 years old) with moderate to severe chronic plaque 
psoriasis who are candidates for systemic treatment. Moderate to severe 
chronic plaque psoriasis is defined by a total PASI score of ≥ 10 and a 
body surface area (BSA) ≥ 10% approaching   a described European 
consensus.
Inclusion criteria
Patients eligible for inclusion in this study have to fulfill all of the following 
criteria:
1.
Men or women at least 18 years of age at the time of Screening.
2.
Chronic plaque-type psoriasis diagnosed for at least 6 months 
prior to Screening and candidate for systemic therapy.
3.
Moderate to severe psoriasis at Baseline as evidenced by: 

PASI ≥ 10 and

IGA mod 2011 score of 3 or higher (based on a scale of 
0 to 4) and

BSA affected by plaque-type psoriasis of ≥ 10%. 
4.
Patients must be able to understand and communicate with the 
Investigator and comply with the requirements of the study and 
must give a written, signed and dated informed consent before 
any study related activity is performed. Where relevant, a legal 
representative will also sign the informed consent form (ICF)
according to local laws and regulations.
Exclusion criteria
Patients fulfilling any of the following criteria will not be eligible for 
inclusion in this study. No additional exclusions may be applied by the 
Investigator in order to ensure that the study population is representative 
of all eligible patients.
1. History of exposure to any biologic drug taken for the treatment 
of chronic plaque psoriasis or any other indication including but 
not limited to anti-tumor necrosis factor (TNF) alpha, 
anti-interleukin (IL)12/23, or any anti-IL-17A or IL-17A receptor 
(IL-17AR) antibody.
2. Use of any other investigational drug within 4 weeks prior to 
Baseline or within a period of 5 half-lives of the investigational 
drug, whichever is longer. 
3. History of hypersensitivity to any of the study drugs or to drugs of 
similar chemical classes including latex hypersensitivity. 
4. Forms of psoriasis other than chronic plaque-type (eg, pustular, 
erythrodermic and guttate psoriasis).
5. Drug-induced psoriasis (ie, new onset or current exacerbation 
 

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from beta-blockers, calcium channel inhibitors or lithium).
6. Ongoing use of prohibited psoriasis treatments (eg, topical or 
systemic corticosteroids, ultraviolet (UV) therapy).
7. Ongoing use of other non-psoriasis prohibited treatments. 
Washout periods detailed in the protocol have to be adhered to. 
All other prior non-psoriasis concomitant treatments must be at a 
stable dose as detailed in the protocol before initiation of study 
drug.
8. 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).
9. Women of child-bearing potential, defined as all women 
physiologically capable of becoming pregnant, unless they are 
using effective methods of contraception during entire study or 
longer if required by locally approved prescribing information 
(e.g. in EU 20 weeks). Effective contraception methods include:

Total abstinence (when this is in line with the preferred and 
usual lifestyle of the patient. Periodic abstinence (eg,
calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of 
contraception.

Female sterilization (have had surgical bilateral 
oophorectomy with or without hysterectomy) or tubal 
ligation at least 6 weeks before taking study drug.

In case of oophorectomy alone, only when the reproductive 
status of the woman has been confirmed by follow-up 
hormone level assessment.

Male 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.

Barrier methods of contraception: condom or occlusive cap 
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository.

Use of oral, injected or implanted hormonal methods of
contraception or other forms of hormonal contraception that
have comparable efficacy (failure rate < 1%), for example,
hormone vaginal ring or transdermal hormone
contraception.

Placement of an intrauterine device (IUD) or intrauterine 
system (IUS).

In case of use of oral contraception women should have 
been stable on the same pill for a minimum of 12 weeks 
before taking study drug.
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 
(eg, age appropriate, history of vasomotor symptoms) or have 
had surgical bilateral oophorectomy (with or without 
hysterectomy) or tubal ligation at least 6 weeks ago. In the case 
of oophorectomy alone, only when the reproductive status of 
 

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the woman has been confirmed by follow-up hormone level 
assessment is she considered not of child bearing potential.
10.Active ongoing inflammatory diseases other than psoriasis that 
might confound the evaluation of the benefit of secukinumab 
therapy.
11.Underlying condition (including, but not limited to metabolic, 
hematologic, renal, hepatic, pulmonary, neurologic, endocrine, 
cardiac, infectious or gastrointestinal conditions) which, in the 
opinion of the Investigator, significantly immunocompromises the 
patient and/or places the patient at unacceptable risk for 
receiving an immunomodulatory therapy.
12.Investigator discretion should be used for patients with pre-
existing or recent-onset central or peripheral nervous system 
demyelinating disorders.
13.Significant medical problems, including but not limited to the 
following: uncontrolled hypertension (systolic blood pressure 
≥160 mmHg and/or diastolic blood pressure ≥ 95 mmHg), 
congestive heart failure (New York Heart Association [NYHA] 
status of class III or IV).
14.Serum creatinine level exceeding 2.0 mg/dL (176.8 µmol/L) at 
Screening.
15.Total white blood cell (WBC) count < 2500/µL, platelets 
< 100 000/µL, neutrophils 1500/µL or hemoglobin < 8.5 g/dL, at 
Screening.
16.Active systemic infections during the 2 weeks prior to Baseline
(exception: common cold) or any infection that reoccurs on a 
regular basis.
17.History of an ongoing, chronic or recurrent infectious disease, or 
evidence of tuberculosis (TB) infection as defined by a positive 
QuantiFERON TB-Gold test (QFT) at Screening. Patients with a 
positive or indeterminate QFT test may participate in the study if 
full 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).
18.Chest X-ray, computerized tomography (CT) scan, or magnetic 
resonance imaging (MRI) with evidence of ongoing infectious or 
malignant process, obtained within 12 weeks prior to Baseline, 
and evaluated by a qualified physician.
19.Past medical history record of, or current infection with, human 
immunodeficiency virus (HIV), hepatitis B virus or hepatitis C
virus prior to Baseline.
20.History of lymphoproliferative disease or any known malignancy 
or history of malignancy of any organ system within the past 5 
years (except for skin Bowen’s disease, or basal cell carcinoma 
or actinic keratoses 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).
21.Current severe progressive or uncontrolled disease which in the 
judgment of the Investigator renders the patient unsuitable for the 
study or puts the patient at increased risk (eg, myocardial 
 

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infarction within 26 weeks prior to Baseline).
22.Inability or unwillingness to undergo repeated venipuncture (eg, 
because of poor tolerability or lack of access to veins).
23.Any medical or psychiatric condition which, in the Investigator’s 
opinion, would preclude the patient from adhering to the protocol 
or completing the study per protocol.
24.History or evidence of ongoing alcohol or drug abuse within the 
last 6 months prior to Baseline.
25.Plans for administration of live vaccines during the study period 
or in the 6 weeks prior to Baseline. 
26.Not willing to limit UV light exposure (eg, sunbathing and/or the 
use of tanning devices) during the course of the study.
Investigational and 
reference therapy
Secukinumab 150 mg will be provided in 1 mL prefilled syringes (PFS) for 
s.c. injection. Secukinumab 300 mg (2 × PFS of the 150 mg dose) will be 
self-administered by the patient. The study drug supplies will be open 
label. 
Treatment period 1 (Baseline to Week 24): 

Secukinumab 300 mg s.c. will be self-administered at Baseline, once 
weekly at Weeks 1, 2 and 3, and thereafter every 4 weeks, starting 
from Week 4 (ie, Week 4, 8, 12, 16 and 20). 
Treatment period 2 (Week 24 to Week 52): 
At Week 24, patients with at least PASI 90 response will be randomly 
assigned on a 1:1 basis to Group 1 or Group 2 as follows:

Group 1: secukinumab 300 mg s.c. every 4 weeks (Week 24, 28, 32, 
36, 40, 44 and 48).

Group 2: secukinumab 300 mg s.c. every 6 weeks (Week 24, 30, 36, 
42 and 48).
At Week 24, patients with a PASI response of 75 but not PASI 90 will be 
randomly assigned on a 1:1 basis to Group 3 or Group 4 as follows:

Group 3: secukinumab 300 mg s.c. every 4 weeks (Week 24, 28, 32, 
36, 40, 44 and 48).

Group 4: secukinumab 300 mg s.c. every 2 weeks (Week 24, 26, 28, 
30, 32, 34, 36, 38, 40, 42, 44, 46 and 48).
Efficacy assessments
The following assessments will be performed:

IGA mod 2011

PASI
Patient related outcomes (PRO) will be assessed using the following 
health related quality of life (HRQoL) assessments:

DLQI©

Patient’s assessment of pain, itching and scaling

EQ-5D©

WPAI-PSO
Safety assessments
Safety will be assessed via the monitoring of physical examinations, vital 
signs, routine laboratory (clinical chemistry including urinalysis and 
hematology) data and adverse events (AEs).
Other assessments
The correlation between pharmacokinetic (PK) data and efficacy 
outcomes will also be assessed. 
 

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Data analysis
The Full Analysis Set for Treatment Period 2 of PASI 90 Responders 
(FAS-P90R) will include all patients who are rated as PASI 90 responders 
at Week 24, are randomized to treatment Group 1 or Group 2, and who 
received at least one dose of study drug at- or after Week 24.
The primary variable is the maintenance of the PASI 90 response rate at 
Week 52 in the FAS-P90R, ie the rate of patients who maintain their PASI 
90 response assessed at Week 24 also at Week 52. The aim of the 
primary analysis for this study will be to demonstrate the non-inferiority of 
the 6-weekly dosing group compared to the 4-weekly dosing group, with 
respect to the primary endpoint in the FAS-P90R. The primary analysis 
will be performed comparing dosing groups (Group 1 vs Group 2) with 
respect to the primary efficacy variable in a logistic regression model with 
the factors treatment, country, body weight (< 90 kg or ≥90 kg), and 
PASI 90 response (Y/N) at Week 16. The
odds ratio with its 
corresponding 95% confidence interval (CI) will be given (please notice 
that the upper limit of a 2-sided 95% CI is identical to the upper limit of a 
1-sided 97.5% CI, which would correspond to a 1-sided test with a 
significance level of 2.5%). Additionally, a (1-sided) p-value for the shifted 
null-hypothesis will be computed.
The key secondary variable is the PASI 90 response rate at Week 52 in 
the FAS-P75P, ie, the proportion of patients with a PASI 75 response but 
also less than a PASI 90 response at Week 24 who achieve a PASI 90 
response at Week 52. The key secondary analysis of this study will be to 
demonstrate superiority of the shortened 2-weekly dosing group
compared to the 4-weekly dosing group in the FAS-P75P.
This analysis will be performed comparing dosing groups (Group 3 vs 
Group 4) with respect to the key secondary variable in a logistic 
regression model with the factors treatment, country and PASI response 
(75% to 82% or 83% to 89%) at Week 24. The odds ratio with its 
corresponding 95% CI and p-value will be presented. The key secondary 
analysis will be included in a confirmatory testing strategy. 
For the safety evaluation, the patient groups of i/ PASI 90 responders and 
ii/ PASI 75 but not PASI 90 responders will be pooled; therefore, only 
3 groups will be compared: 

secukinumab 300 mg s.c. every 2 weeks (patients from Group 4).

secukinumab 300 mg s.c. every 4 weeks (patients from Group 1 
pooled with Group 3).

secukinumab 300 mg s.c. every 6 weeks (patients from Group 2).
Patients will be analyzed according to the treatment they received. 
Treatment emergent AEs will be summarized by system organ class 
(SOC) and preferred term.
Key words
Open-label, randomized, blinded assessment, chronic plaque psoriasis, 
PASI, secukinumab, monoclonal antibody
 

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1
Introduction
1.1
Background 
Psoriasis is a chronic, immune-mediated inflammatory disease that affects up to 3% of the 
population worldwide (Jacobson et al 2011). Psoriasis typically manifests as plaques 
(Lebwohl 2003) that occur most commonly on the skin of the elbows and knees. Plaques can 
affect any area, including the palms and soles (Pettey et al 2003); fingernails and toenails are 
also commonly affected (Radtke et al 2011). The efficacy of systemic therapy with biologics 
in the treatment of moderate-to-severe plaque psoriasis is well established (Christophers et al 
2013; Herrier 2011). 
Secukinumab is a fully human immunoglobulin G1/κ-class (IgG) anti-interleukin (IL)-17A 
monoclonal antibody that selectively suppresses the inflammatory cascade induced by the 
cytokine IL-17A. Secukinumab has demonstrated efficacy and safety for the treatment of 
moderate-to-severe plaque psoriasis (Langley et al 2014; Paul et al 2014). A large proportion 
of patients (71%) with moderate to severe plaque psoriasis achieved a Psoriasis Area and 
Severity Index (PASI) 90 response after 16 weeks of treatment with secukinumab 300 mg s.c.
Subcutaneous injections were administered every 4 weeks with the exception of the first 4 
weeks of treatment when the drug was given weekly. A sustainable drug response was still 
evidenced at Week 52 with a PASI 90 response rate of 63%. The Investigator Global 
Assessment modified 2011 (IGA mod 2011; Langley et al 2013) 0/1 response rate was 
comparable to the PASI 90 response with approximately 74% and 64% of patients achieving a 
clinical response at Week 16 and Week 52, respectively (pooled data from CAIN4572302 and 
CAIN4572303 pivotal studies). The Phase 3 clinical trials data support the use of
secukinumab 300 mg s.c. every 4 weeks for maintenance of clinical response.
Optimizing maintenance dosing regimens for patients treated with (biologic) drugs offers 
many benefits, such as minimizing patients’ exposure to the drug substance, increasing drug 
compliance and lessening economic burdens while keeping an acceptable clinical response. 
This principle has been investigated in a number of studies mainly in rheumatic disorders with 
currently available biological drugs. One psoriatic arthritis study demonstrated that most 
patients maintained their initial clinical response when the maintenance dose interval was 
prolonged from 2 weeks to 4 weeks after an initial induction period (Cantini et al 2012). 
Similar dose reductions have been reported in rheumatoid arthritis (den Broeder et al 2002) 
and in ankylosing spondylitis patients (Lee SH et al 2008). In these studies the original dosing 
interval was maintained but the dose was reduced. Dermatologists, like rheumatologists, are 
looking for a similar reduction and optimization in drug exposure once a patient has cleared, 
or almost cleared, skin from psoriasis. However, only one double-blind study investigating 
dose reduction of a biologic drug in psoriasis was identified in the literature which showed 
that the initial clinical response was maintained despite reducing the dose by 50% after 
12 weeks (Papp et al 2005). 
In contrast, patients not responding adequately to a biologic treatment can benefit from an 
increased frequency of drug dosing. Shortening dose intervals (off-label use) for marketed 
substances can be assumed to happen frequently especially in partial responders in daily 
practice. One study described that reducing the dosing interval (of ustekinumab) from 
12 weeks to 8 weeks in partial responders had a good clinical effect (Kimball et al 2012). 
 

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Similarly, another study demonstrated that shortening the dose interval (of adalimumab) from 
2 weeks to 1 week was effective in patients who were refractory to both non-biological and 
biological treatment (Papoutsaki et al 2007). 
At the present time clinical studies assessing flexible dosing regimens for long-term 
secukinumab treatment are very rare. A retreatment-as-needed (RAN) approach (ie, 
retreatment at start of relapse) has been assessed as an alternative to maintain response in 
some patients while adjusting drug exposure. The SCULPTURE (CAIN457A2304) study 
compared secukinumab RAN to a fixed-interval regimen (every 4 weeks) for the maintenance 
of efficacy up to 52 weeks in patients who achieved a PASI 75 response at Week 12 with 
secukinumab. The SCULPTURE study did not confirm the RAN dosing regimen as 
non-inferior to a fixed interval dosing regimen of secukinumab in plaque-type psoriasis even 
though both regimens led to clinically meaningful response rates. The fixed-dose interval 
regimen was shown to have clear benefits compared to the RAN regimen for sustained 
efficacy in the treatment of psoriasis (Mrowietz et al 2013). Consistently across efficacy 
measures, patients in the fixed-interval groups showed increased maintenance of response 
over those in the RAN groups. These results indicate that fixed-dose interval regimens are 
preferable over RAN regimens for maintenance dose regimens of secukinumab. Varying the 
duration of the fixed-dose interval of secukinumab in the maintenance period could
potentially allow a better alternate approach for flexible dosing than the RAN approach and 
this will be investigated in the current study. 
1.2
Purpose 
The primary purpose of this study is to assess the efficacy and safety of different maintenance 
dosing regimens in patients who have achieved a PASI 90 response after 24 weeks of 
treatment with secukinumab 300 mg s.c. The current study will assess if an extended dose 
interval (every 6 weeks vs every 4 weeks) will allow psoriasis patients who achieve PASI 90 
after 24 weeks of secukinumab treatment to maintain this response for a further 28 weeks 
(52 weeks in total). 
The study will also assess whether dose intensification through a shortened dose interval 
(every 2 weeks vs every 4 weeks) will allow patients who are PASI 75 responders but not 
PASI 90 responders after 24 weeks of treatment with secukinumab 300 mg s.c. to achieve the 
PASI 90 target after a further 28 weeks of treatment in the maintenance period. In addition, 
patient reported outcomes (PRO) data will be collected to explore the effect of secukinumab 
on health-related quality of life (HRQoL) and work productivity.
2
Study objectives
2.1
Primary objective
The primary objective is to demonstrate in the patient pool of PASI 90 responders at Week 24 
that secukinumab 300 mg s.c. every 6 weeks treatment is non-inferior to secukinumab 300 mg 
s.c. every 4 weeks treatment with respect to maintaining a PASI 90 response rate at Week 52.
2.2
Secondary objectives
The key secondary objective is to demonstrate in the patient pool of PASI 75 responders who 
do not reach a PASI 90 response at Week 24 that secukinumab 300 mg s.c. administered 
 

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every 2 weeks is superior to secukinumab 300 mg s.c. administered every 4 weeks at Week 52 
based on the PASI 90 response rate.
Other secondary objectives are as follows: 

Evaluate the proportion of PASI 50, PASI 75, PASI 100 and IGA mod 2011 0/1 responder 
rates at Week 52.

Evaluate the course of mean PASI over time from Week 24 to Week 52.

Evaluate the effect of different maintenance treatment frequencies on PROs: Dermatology 
Life Quality Index (DLQI), EuroQOL 5-Dimension Health Questionnaire (EQ-5D©), 
Work Productivity and Activity Impairment Questionnaire-Psoriasis (WPAI-PSO), and 
the patient’s assessment of pain, itching and scaling.
2.3
Exploratory objectives

Evaluate the proportion of PASI 50, PASI 75, PASI 90, PASI 100 and IGA mod 2011 0/1 
responders at Week 24.

Evaluate the time to achieve clear or almost clear skin based on PASI 90 when receiving 
secukinumab 300 mg s.c. every 2 weeks compared to every 4 weeks from Week 24 to 
Week 52.

Evaluate time to first loss of PASI 75 response when receiving secukinumab every 
2 weeks compared to every 4 weeks from Week 24 until Week 52.

Evaluate the safety and tolerability of different maintenance treatment regimens of 
secukinumab 300 mg s.c.

Explore the correlation between the pharmacokinetic (PK) data and efficacy outcomes.
Other exploratory objectives for patients with PASI 90 response at Week 24 are as follows:

Assess the time to loss of PASI 90 response.

Assess the time to loss of IGA mod 2011 0/1 response.
3
Investigational plan
3.1
Study design
This is a randomized, open-label with blinded-assessment, multicenter, 52-week study to 
evaluate the efficacy (based on PASI 90), safety and tolerability of secukinumab 300 mg s.c.
in patients with moderate to severe chronic plaque psoriasis. This study consists of 
2 treatment periods: a 24-week run-in treatment period (Baseline to Week 24) and a 28-week 
maintenance treatment period (Week 24 to Week 52) as indicated in Figure 3-1. 
 

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For Treatment Period 1 (Baseline to Week 24) all patients will receive the same treatment:

Secukinumab 300 mg s.c. will be self-administered at Baseline, once weekly at Week 1, 2 
and 3; and thereafter every 4 weeks starting from Week 4 (ie, Week 4, 8, 12, 16 and 20).
At Week 24, all patients will be assessed in term of PASI response and either randomized to 
one of the 4 treatment groups in Treatment Period 2 (Week 24 to Week 52) or withdrawn 
from the study. 
Patients with at least a 90% reduction in PASI score from Baseline will be randomized at 
Week 24 on a 1:1 basis to Group 1 or Group 2:

Group 1 (recommended maintenance treatment): secukinumab 300 mg s.c. every 4 weeks 
(Week 24, 28, 32, 36, 40, 44 and 48).

Group 2 (experimental dosing maintenance treatment): secukinumab 300 mg s.c. every 
6 weeks (Week 24, 30, 36, 42 and 48).
Patients with less than 90% reduction in PASI score from Baseline at Week 24 but who 
achieved at least a 75% reduction in PASI score from Baseline are eligible for dose frequency 
intensification and will be randomized on a 1:1 basis to either Group 3 or Group 4:

Group 3 (recommended maintenance treatment): secukinumab s.c. 300 mg every 4 weeks 
(Week 24, 28, 32, 36, 40, 44 and 48).

Group 4 (experimental maintenance treatment): secukinumab s.c. 300 mg every 2 weeks 
(Week 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46 and 48).
At Week 52, patients from Group 3 and Group 4 will enter into a treatment-free follow-up
period until Week 60. From the last study drug administration at Week 48 to Week 60 
(12 weeks) patients will not be allowed to take any study drug. At the Week 60 visit, relapse, 
rebound and safety will be explored.
At Week 24, patients with a reduction in PASI score from Baseline of less than 75% will not 
be eligible for randomization and will be discontinued from the study.
Randomization will be stratified by body weight collected at the Randomization Visit 
(< 90 kg or ≥90 kg).
The study drug will be self-administered by patients throughout the study. Study drug 
administration will occur at the study center for all study visits in Treatment Period 1; and at 
the study center or at the patient’s home in Treatment Period 2. Self-administrations at every 
study center visit should be supervised by the study center personnel to ensure a correct study 
drug application and proper preparation of the patient for the home administration without 
study center personal supervision. If needed a caregiver of the patient can be trained for home 
administration to provide support. Home drug administration using the same injection device 
(ie, pre-filled syringes [PFS]) was introduced in previous secukinumab Phase 3b clinical 
studies, eg the CAIN457A2312, CAIN457A2313, and CAIN457A3301 studies. To allow for 
comparable treatment group data at fixed study visits, patients will be trained for home drug 
administration prior to Treatment Period 2. 
A blinded PASI assessor who has no access to the randomization details must perform all 
PASI and IGA mod 2011 efficacy assessments for Treatment Period 2 (Week 24 to Week 52). 
To reduce measurement variability it is recommended that the same blinded PASI assessor 
performs all PASI and IGA mod 2011 assessments for a single patient.
 

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The blinded PASI assessor must not participate in any study-related activities that could 
compromise the blinding and should solely concentrate on the skin examination for 
PASI and IGA mod 2011 assessments. For more details please refer to Section 5.4. 
Safety will be assessed throughout the study through the monitoring of AEs, SAEs, 
electrocardiograms (ECGs), vital signs and laboratory data. 
Figure 3-1
Study design

randomization of responder (PASI ≥ 90)

randomization of responder (75 ≤PASI < 90)
BL:
baseline
NR:
non-responder (PASI < 50)
PE:
primary endpoint
PR:
partial responder (50 ≤ PASI < 75)
 

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3.2
Rationale of study design
The secukinumab 300 mg s.c. every 4 weeks dose regimen has been evaluated extensively in 
a Phase 3 clinical trial program and showed strong sustainability of efficacy response with a 
good safety profile up to 52 weeks of treatment. Further knowledge for long term 
maintenance treatment flexibility for the optimal effective dose is a medical need that 
dermatologists are looking for with any biologic psoriasis drug in order to administer to the 
patient the right dose and regimen at the right treatment time.
The main reason for choosing the study design is to research in optimized maintenance 
treatment options to minimize drug exposure for secukinumab in patients cleared or almost 
cleared (PASI 90) from psoriasis while maintaining an acceptable clinical response and 
comparable safety profile. 
Another reason for the study design is to examine if PASI 75 responders could benefit in 
terms of efficacy from an increased dosing interval for the study drug with a comparable 
safety profile. In the CAIN457A2212 study psoriasis patients have been exposed to an 
increased drug exposure without detection of any safety-related signals.
Taken together the rationale for the study is to explore options for individualizing 
maintenance treatment.
The CAIN457A2304 study, part of the secukinumab Phase 3 program, has assessed a RAN
(retreatment at the start of relapse) approach as an alternative to maintain treatment response 
in some patients when secukinumab response has been achieved after 12 weeks. The 
fixed-dose interval regimen every 4 weeks was shown to have a clear benefit compared to the 
RAN regimen for sustained efficacy in the treatment of psoriasis (Mrowietz et al 2013).
At the present time, there is still a need for clinical study designs assessing flexible dosing 
options for long-term biologic treatment of psoriasis for patients who have achieved clear or 
almost clear skin under treatment, and additionally, when a certain drug response is achieved 
that could be optimized towards complete clearance of the symptoms. This more 
individualized maintenance treatment has become a treatment option to assess for 
secukinumab 300 mg s.c. since it has shown speed, strength and sustainability with 74.3% of 
biologic naïve psoriasis patients achieving PASI 90 at Week 24. At Week 52, 81.8% of the 
patients who achieved PASI 90 at Week 24 maintained clear or almost clear skin from 
psoriasis showing a high level of treatment sustainability in the maintenance period. Pooled 
data from the Phase 3 studies  showed that 87.6% of biologic-naïve patients achieved at least 
the PASI 75 criterion at Week 24 (95% confidence interval (CI) ranged from 84.7% to 90.1%) 
and could therefore be regarded as responders to secukinumab. At Week 24, 5.9% of patients 
achieved a PASI 50 partial response but no PASI 75 response and therefore did not fully 
benefit from secukinumab, while 6.5% of patients were non-responders.
This study is designed to assess the primary objective of allowing more treatment flexibility 
(extended dose interval to every 6 weeks) with less drug exposure in moderate to severe 
psoriasis patients who achieved a PASI 90 response after 24 weeks of secukinumab 300 mg
s.c. Furthermore, this study is designed to assess the key secondary objective of allowing 
more treatment flexibility (shortened treatment interval to 2 weeks) in moderate to severe 
psoriasis patients who achieved a PASI 75 but not a PASI 90 response after 24 weeks of 
secukinumab 300 mg s.c. every 4 weeks. The study will also evaluate the safety and 
 

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tolerability of secukinumab. In addition, the study will collect data on PROs to explore the 
effect of secukinumab 300 mg s.c. maintenance treatment on patient’s health related quality of 
life and work productivity.
In this study, only secukinumab verum injections will be administered. This will more closely 
reflect a real-life situation for patients than, for example, using a double-blinded, double 
dummy study design that would require secukinumab placebo injections. The blinded assessor 
approach is enabling to capture cogent efficacy data deriving from Investigator assessments. 
In addition, the design supports for interpreting these Investigator assessments in the context 
of 
a 
patient’s 
daily 
life 
and 
social 
function 
measured
by 
PROs 
(EMEA/CHMP/EWP/139391/2004). 
The treatment-free follow-up period will be limited to treatment Group 3 and Group 4 as 
treatment-free follow-up period data for drug exposures up to 300 mg s.c. every 4 weeks in 
the maintenance phase have already been extensively reported for the Phase 3 secukinumab 
program studies.
Rationale for choice of non-inferiority margin and primary endpoint
Statistical projections to support the choice of non-inferiority margin for this study are 
difficult as Week 24 to Week 52 data are not available for PASI 90 response rates in patients 
treated with the experimental dosing frequencies scheduled for this study. However, for the 
active controlled study CAIN457A2304 in the secukinumab development program the 
non-inferiority margin was set to 15%. Based on clinical judgment, a non-inferiority margin 
of 15% is justifiable also, especially when taking into account the maintenance phase endpoint 
and the maintenance responder rate (ie, 81.8% of patients achieving a PASI 90 response at 
Week 24 are still PASI 90 responders at Week 52) observed in the clinical trial program with 
secukinumab 300 mg s.c. to date. This non-inferiority margin has been accepted for the 
CAIN4572304 study by participating regulatory agencies in the US, EU and Japan.
Similar study designs for drug exposure reduction for other biologic treatments in moderate to 
severe psoriasis patients are very
limited. In the rheumatoid arthritis indication,
non-inferiority margins in studies with drug exposure reductions have been recently accepted 
up to a 20% non-inferiority margin for efficacy endpoints (den Broeder et al 2013,
Mariette et al 2014).
The non-inferiority margin for the primary endpoint is also comparable to other efficacy 
endpoints of the mentioned studies and is considered a clinically balanced choice taking into 
account the likelihood to maintain a PASI 90 response rate in the study population treated 
with a prolonged dosing regimen (secukinumab Phase 3 program, pooled data of biologic 
naïve patients). It should be noted in this context that the PASI scoring system, even if used as 
one of the most frequent ones to assess psoriasis drug efficacy in clinical trials, is known to be 
complex and a certain measurement system variability applies (Costa de Faria et al 2010).
Sample size details are provided in Section 9.7.
3.3
Rationale of 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 have been demonstrated in the Phase 3 clinical trial program. The 300 mg s.c.
dose of secukinumab delivered the most clinically meaningful benefit to patients compared to 
 

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the 150 mg s.c. dose across all pivotal studies for all time points (Week 12 to Week 52) as 
described in Section 1. Therefore, a maintenance dose of 300 mg s.c. has been selected for all 
treatment groups proposed for this study. The dose interval for the initial treatment period (ie,
once every week for the first 4 weeks, followed by once every 4 weeks until Week 24) has 
been selected as the Phase 3 clinical trial program demonstrated a strong efficacy response to 
treatment at this dose interval.
A more prolonged maintenance dose interval (every 6 weeks for Group 2) has been selected 
for patients who achieve clear or almost clear skin from psoriasis after 24 weeks of treatment 
(PASI ≥ 90) in order to establish if this dose interval is non-inferior to the current proven 
maintenance dose interval (ie, every 4 weeks), which is selected as the comparator group in 
this study.
A shortened dose interval (every 2 weeks) has been selected for Group 4 for patients who are 
responders but fail to achieve a response of PASI ≥ 90 after 24 weeks to establish if this dose 
interval is superior to the current proven maintenance dose interval (every 4 weeks) and to 
assess if this dose interval would allow patients to achieve the target response of PASI ≥ 90 
after a further 28 weeks of treatment. 
Although secukinumab 300 mg s.c. every 2 weeks has not been tested yet in a maintenance 
treatment period, no safety concerns are expected with this dose regimen based on the 
secukinumab results reported in the clinical trial program to date (Papp et al 2011). A 
24-week initial treatment period (Baseline to randomization at Week 24) has been selected as 
the Phase 3 clinical trial program demonstrated a strong response to treatment. A 28-week 
maintenance treatment period (Week 24 to Week 52) has been selected as the Phase 3 clinical 
trial program demonstrated a sustainable high efficacy response for secukinumab 300 mg s.c. 
starting at Week 16 and remaining very stable until at least Week 24 under treatment (Langley 
et al 2014). 
Randomization will be stratified by body weight collected at the Randomization Visit 
(< 90 kg or ≥90kg) to exclude corresponding imbalances in any patient group of this study. 
The same threshold split (90 kg) was used for the discourse with the United States Food and 
Drug Administration (FDA) and European Medicines Agency (EMA) and was studied
extensively in the secukinumab Phase 3 program.
Pre-filled syringes have been selected for secukinumab s.c. administration in this study as 
these have been successfully used by patients in the Phase 3 clinical studies, which showed 
the use of PFS was safe and well tolerated. Self-injection with the PFS, following the utilized 
instructions for use, showed no significant safety hazards and was found to be acceptable to 
study participants and to the competent authorities for other secukinumab studies
(CAIN457A2312, CAIN4572312 and CAIN457A3301).
3.4
Rationale for choice of comparator
This study was designed primarily to demonstrate the non-inferiority of secukinumab 300 mg
s.c. every 6 weeks compared to secukinumab 300 mg s.c. every 4 weeks when administered as 
a maintenance treatment. Therefore, no placebo or other comparator treatment will be 
included in the study. 
 

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3.5
Purpose and timing of interim analyses/design adaptations
Not applicable. 
3.6
Risks and benefits
An extensive Phase 3 program demonstrated secukinumab to be very effective in treating 
plaque psoriasis, with 300 mg s.c. being the dose that delivered the most clinically meaningful 
benefit to patients with respect to achievement of almost clear to clear skin, improved quality 
of life (QoL), speed of onset of action, and sustainability of symptom relief. The majority of 
patients treated with this dose achieved clear to almost clear skin, as shown by PASI 90 
response and IGA mod 2011 0/1 response, with a corresponding increase in DLQI response
(Langley et al 2014; Paul et al 2014).
Secukinumab was generally safe and well-tolerated. The most frequently reported AEs were 
infections, especially upper respiratory tract infections with secukinumab relative to placebo. 
Related to the known mode of action, there was an increase in mucosal or cutaneous 
candidiasis infection with secukinumab compared to placebo, but the cases were generally 
mild or moderate in severity, non-serious, easily manageable, and responsive to standard 
treatment and did not lead to study discontinuation.
There was a small increase in mild to moderate neutropenia cases with secukinumab 
compared to placebo. Common Toxicity Criteria for AE grade 3 neutropenia (< 1.0 to 0.5 × 
109/L) was uncommonly observed with secukinumab, most cases were transient and 
reversible without a temporal relationship to infections. 
Hypersensitivity reactions including urticaria and one case of anaphylactic reaction to 
secukinumab were also observed in clinical studies. The removable needle cap of the pre-
filled syringe 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 pre-filled syringes in latex 
sensitive individuals has not been studied and there is therefore a potential risk of 
hypersensitivity reactions which cannot be completely ruled out.
Taking into account the individual risks as outlined above, the expected risk profile of 
secukinumab from a mechanism of action perspective is anticipated to be similar or improved 
compared to the approved inflammatory cytokine-targeting therapies. The risk to patients in 
this study will be minimized by compliance with the eligibility criteria, close clinical 
monitoring and extensive guidance to the Investigators provided in the current version of the 
Investigator’s Brochure.
From the standpoint of the overall risk-benefit assessment, the current study with 
secukinumab is justified.
 

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4
Population
The study population will consist of a representative group of male and female patients 
(≥18 years old) with moderate to severe chronic plaque psoriasis and candidates for systemic 
treatment. Moderate to severe chronic plaque psoriasis is defined by a total PASI score of 
≥10 and a body surface area (BSA) of ≥ 10% approaching a described European consensus 
(Mrowietz et al 2011).
It is planned that approximately 2257 patients will be screened and around 1580 patients will 
be enrolled at Baseline to randomize 570 patients at Week 24 each for Group 1 and Group 2 
(relevant groups for primary objective). Sample size details are provided in Section 9.7. 
Patients who drop out after they have been randomized will not be replaced. If a patient fails 
to be enrolled at Baseline, the patient may be rescreened if it can be assumed that the cause of 
Screening failure is only a temporary constraint. Patients may be screened more than once.
Randomization will be stratified by body weight at Week 24 (randomization visit). The strata 
will be “body weight ≥ 90 kg” or “body weight < 90 kg” for all treatment groups.
4.1
Inclusion criteria
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
1. Men or women at least 18 years of age at the time of Screening.
2. Chronic plaque-type psoriasis diagnosed for at least 6 months prior to Screening and 
candidate for systemic therapy.
3. Moderate to severe psoriasis at Baseline as evidenced by: 

PASI ≥ 10 and

IGA mod 2011 score of 3 or higher (based on a scale of 0 to 4) and

BSA affected by plaque-type psoriasis of ≥ 10%
4. Patients must be able to understand and communicate with the Investigator and comply 
with the requirements of the study and must give a written, signed and dated informed 
consent before any study related activity is performed. Where relevant, a legal 
representative will also sign the ICF according to local laws and regulations.
 

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4.2
Exclusion criteria
Patients fulfilling any of the following criteria will not be eligible for inclusion in this study. 
No additional exclusions may be applied by the Investigator in order to ensure that the study 
population is representative of all eligible patients.
1. History of exposure to any biologic drug taken for the treatment of chronic plaque 
psoriasis or any other indication including but not limited to anti-tumor necrosis factor 
(TNF) alpha, anti-IL12/23, or any anti-IL-17A or IL-17A receptor (IL-17AR) antibody.
2. Use of any other investigational drug within 4 weeks prior to Baseline or within a period 
of 5 half-lives of the investigational drug, whichever is longer. 
3. History of hypersensitivity to any of the study drugs or to drugs of similar chemical 
classes including latex hypersensitivity. 
4. Forms of psoriasis other than chronic plaque-type (eg, pustular, erythrodermic and guttate 
psoriasis).
5. Drug-induced psoriasis (ie, new onset or current exacerbation from beta-blockers, calcium 
channel inhibitors or lithium).
6. Ongoing use of prohibited psoriasis treatments (eg, topical or systemic corticosteroids, 
ultraviolet (UV) therapy).
7. Ongoing use of other non-psoriasis prohibited treatments. Washout periods detailed in the 
protocol (Table 5-2) have to be adhered to. All other prior non-psoriasis concomitant 
treatments must be at a stable dose as detailed in the protocol before initiation of study 
drug.
8. 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).
9. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective methods of contraception during entire 
study or longer if required by locally approved prescribing information (e.g. in EU 20 
weeks). Effective contraception methods include:

Total abstinence (when this is in line with the preferred and usual lifestyle of the 
patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception.

Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy) or tubal ligation at least 6 weeks before taking study drug.

In case of oophorectomy alone, only when the reproductive status of the woman has 
been confirmed by follow-up hormone level assessment.

Male 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.

Barrier methods of contraception: condom or occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.

Use of oral, injected or implanted hormonal methods of contraception or other forms 
of hormonal contraception that have comparable efficacy (failure rate < 1%), for 
example, hormone vaginal ring or transdermal hormone contraception.

Placement of an intrauterine device (IUD) or intrauterine system (IUS).
 

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
In case of use of oral contraception women should have been stable on the same pill 
for a minimum of 12 weeks before taking study drug.
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 
(eg, age appropriate, history of vasomotor symptoms) or have had surgical bilateral 
oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In the 
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.
10. Active ongoing inflammatory diseases other than psoriasis that might confound the 
evaluation of the benefit of secukinumab therapy.
11. Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, 
pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions) which, 
in the opinion of the Investigator, significantly immunocompromises the patient and/or 
places the patient at unacceptable risk for receiving an immunomodulatory therapy.
12. Investigator discretion should be used for patients with pre-existing or recent-onset central 
or peripheral nervous system demyelinating disorders.
13. Significant medical problems, including but not limited to the following: uncontrolled 
hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure 
≥95 mmHg), congestive heart failure (New York Heart Association [NYHA] status of 
class III or IV).
14. Serum creatinine level exceeding 2.0 mg/dL (176.8 µmol/L) at Screening.
15. Total white blood cell (WBC) count < 2500/µL, platelets < 100 000/µL, neutrophils 
1500/µL or hemoglobin < 8.5 g/dL, at Screening.
16. Active systemic infections during the 2 weeks prior to Baseline (exception: common cold) 
or any infection that reoccurs on a regular basis.
17. History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis
(TB) infection as defined by a positive QuantiFERON TB-Gold test (QFT) at Screening. 
Patients with a positive or indeterminate QFT test may participate in the study if full 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).
18. Chest X-ray, computerized tomography (CT) scan, or MRI with evidence of ongoing
infectious or malignant process, obtained within 12 weeks prior to Baseline, and evaluated 
by a qualified physician.
19. Past medical history record of, or current infection with, human immunodeficiency virus 
(HIV), hepatitis B virus or hepatitis C virus prior to Baseline.
20. History of lymphoproliferative disease or any known malignancy or history of malignancy 
of any organ system within the past 5 years (except for skin Bowen’s disease, or basal cell 
carcinoma or actinic keratoses 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 
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21. Current severe progressive or uncontrolled disease which in the judgment of the 
Investigator renders the patient unsuitable for the study or puts the patient at increased risk 
(eg, myocardial infarction within 26 weeks prior to Baseline).
22. Inability or unwillingness to undergo repeated venipuncture (eg, because of poor 
tolerability or lack of access to veins).
23. Any medical or psychiatric condition which, in the Investigator’s opinion, would preclude 
the patient from adhering to the protocol or completing the study per protocol.
24. History or evidence of ongoing alcohol or drug abuse, within the last 6 months prior to 
Baseline.
25. Plans for administration of live vaccines during the study period or in the 6 weeks prior to 
Baseline. 
26. Not willing to limit UV light exposure (eg, sunbathing and/or the use of tanning devices) 
during the course of the study.
5
Treatment
5.1
Protocol requested treatment
5.1.1
Investigational treatment
Secukinumab for s.c. injection will be supplied in single boxes each containing 2 PFS of
150 mg secukinumab in a 1 mL liquid formulation.
Each 300 mg dose will be administered as 2 PFS injections of 150 mg secukinumab. 
All study drugs will be labelled appropriately.
5.1.2
Additional study treatment
No additional treatment is requested for this study.
5.2
Treatment groups
For Treatment Period 1 (Baseline to Week 24) all patients will receive the same treatment:

Secukinumab 300 mg s.c. will be self-administered at Baseline, weekly at Week 1, 
Week 2 and Week 3 and every 4 weeks thereafter (ie, Week 4, 8, 12, 16 and 20).
At Week 24, all patients will be assessed in term of PASI response and either randomized to 
one of the 4 treatment groups in Treatment Period 2 (Week 24 to Week 52) or withdrawn 
from the study. 
Patients with at least a 90% reduction in PASI score from Baseline will be randomized at 
Week 24 on a 1:1 basis to Group 1 or Group 2:

Group 1 (recommended maintenance treatment): secukinumab 300 mg s.c. every 4 weeks 
(Week 24, 28, 32, 36, 40, 44 and 48).

Group 2 (experimental dosing maintenance treatment): secukinumab 300 mg s.c. every 
6 weeks (Week 24, 30, 36, 42 and 48).
 

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Patients with less than 90% reduction in PASI score from Baseline at Week 24 but achieved at 
least a 75% reduction in PASI score from Baseline are eligible for dose frequency 
intensification and will be randomized on a 1:1 basis to either Group 3 or Group 4:

Group 3 (recommended maintenance treatment): secukinumab s.c. 300 mg every 4 weeks 
(Week 24, 28, 32, 36, 40, 44 and 48).

Group 4 (experimental maintenance treatment): secukinumab s.c. 300 mg every 2 weeks 
(Week 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46 and 48).
Patients with a reduction in PASI score from Baseline of less than 75% at Week 24 are not 
eligible for randomization and will be discontinued from the study.
5.3
Treatment assignment, randomization 
At the Screening Visit, every patient will be registered in an Interactive Response Technology 
(IRT) system. The Investigator or his/her delegate will ensure that the patient fulfills all the 
inclusion/exclusion criteria. At Baseline, every patient will receive study medication kits 
assigned by the IRT system. 
At the Randomization Visit (Week 24) all patients will be assessed in term of PASI response 
and eligible patients will be randomized by the IRT system to one of the 4 treatment groups in 
Treatment Period 2 (Week 24 to Week 52) or withdrawn from the study. 
Patients with at least a 90% reduction in PASI score from Baseline will be randomized at 
Week 24 on a 1:1 basis to Group 1 or Group 2:

Group 1 (recommended maintenance treatment): secukinumab 300 mg s.c. every 4 weeks 
(Week 24, 28, 32, 36, 40, 44 and 48).

Group 2 (experimental dosing maintenance treatment): secukinumab 300 mg s.c. every 
6 weeks (Week 24, 30, 36, 42 and 48).
Patients with less than 90% reduction in PASI score from Baseline at Week 24 but achieved at 
least a 75% reduction in PASI score from Baseline are eligible for dose frequency 
intensification and will be randomized on a 1:1 basis to either Group 3 or Group 4:

Group 3 (recommended maintenance treatment): secukinumab s.c. 300 mg every 4 weeks 
(Week 24, 28, 32, 36, 40, 44 and 48).

Group 4 (experimental maintenance treatment): secukinumab s.c. 300 mg every 2 weeks 
(Week 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46 and 48).
Patients with a reduction in PASI score from Baseline of less than 75% at Week 24 are not 
eligible for randomization and will be discontinued from the study. The IRT will assign a 
randomization number to the patient, which will be used to link the patient to a treatment 
group and study drug to be dispensed to the patient. The randomization number will not be 
communicated to the IRT user. 
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from patients and Investigator staff. A patient 
randomization list will be produced by the IRT provider using a validated system that 
automates the random assignment of Patient Numbers to randomization numbers. These 
randomization numbers are linked to the different treatment groups, which in turn are linked 
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A separate medication list will be produced under the responsibility of Novartis Drug Supply 
Management using a validated system that automates the random assignment of medication 
numbers to packs containing the study drug.
The randomization scheme for patients will be reviewed and approved by a qualified team 
member.
Further details will be described in the IRT manual.
5.3.1
IRT Stratification
Randomization will be stratified at the Week 24 visit (Randomization) by body weight. This 
stratification ensures balanced allocation of patients to treatment groups within the weight 
strata. The strata will be “body weight ≥ 90 kg” or “body weight < 90 kg.” All treatment 
groups will be stratified by body weight assessed at Week 24. The randomization scheme for 
patients will be reviewed and approved by a randomization expert.
5.4
Treatment blinding 
The study drug will be self-administered by the patient in an open-label fashion as described 
in Section 5.5. A blinded PASI assessor who has no access to the randomization details must
perform all PASI and IGA mod 2011 efficacy assessments for Treatment Period 2 (Week 24 
to Week 52). To reduce measurement variability, it is recommended that the same blinded 
PASI assessor performs all PASI and IGA mod 2011 assessments for a single patient. 
The blinded PASI assessor must not participate in any study-related activities that could 
compromise the blinding and should solely concentrate on the skin examination for 
PASI and IGA mod 2011 assessments.
The blinded assessor will know at Week 24 if a patient will achieve the PASI 90 criterion or 
not. However, in the analysis phase of the study, PASI and IGA mod 2011 data for Group 1 
will be compared only with corresponding data from Group 2 (both groups represent the 
patient pool meeting a PASI 90 response at Week 24). PASI and IGA mod 2011 data from 
Group 3 and Group 4 will be treated separately in the study analysis. 
A PASI assessor should be qualified by education, training and experience (eg, a physician). 
Training for the blinded assessor will be offered at the Investigator Meeting and/or during 
study center initiation and/or at the latest before the blinded PASI assessor will do the first 
assessment. The training should be documented appropriately. If the blinded assessor 
observes a potential safety event (eg, an AE) during the assessments he/she must inform, 
without delay, the unblinded team that has all the available patient information. The unblinded 
team is responsible to further examine the transferred observation without delay. All 
observations need to be documented appropriately by the blinded assessor including the 
transfer of the information to the unblinded team. The unblinded team is responsible to 
subsequently report any potential safety event to the Novartis. See also Section 7.
The blinded PASI assessors will use electronic devices to document and report PASI and 
IGA mod 2011 data. Data will be collected in a central database separated from the main 
clinical database to mitigate risks for unblinding events and reduce cross-team interactions. 
The results of the PASI and IGA mod 2011 assessments will be sent electronically to Novartis 
or a designated Contract Research Organization (CRO). Details of the process are described in 
a user manual and will be part of the blinded assessor training.
 

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All remaining assessments will be performed in an unblinded manner.
5.5
Treating the patient 
5.5.1
Patient numbering 
Each patient is uniquely identified by a Patient Number which is composed by 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 available 
sequential number by the Investigator. At each study center, the first patient is assigned 
Patient Number 1, and subsequent patients are assigned consecutive numbers (eg, the second 
patient is assigned Patient Number 2, and the third patient is assigned Patient Number 3).
The Investigator or his/her staff will contact the IRT and provide the requested identifying 
information for the patient to register the patient into the IRT. The study center should select 
the electronic Case Report Form (eCRF) book with a matching Patient Number from the 
electronic data capture (EDC) system to enter data. If the patient fails to be treated for any 
reason, the IRT should be notified that the patient was not treated. 
At least the following information should be completed on the eCRFs for a patient who screen 
fails: demography, informed consent, inclusion/exclusion criteria, AEs (if applicable), SAEs 
(if applicable), death (if applicable), withdrawal of consent (if applicable) and patient 
screening details.
If a patient is rescreened for the study, the patient must sign a new ICF and will be issued a 
new Patient Number. The date of the new informed consent signature must be entered in the 
eCRF. Informed consent for a rescreened patient as for a newly screened patient must be 
obtained prior to performing any study related assessments or collecting any data for the 
Screening Visit. There is no limit on the number of times a patient can be rescreened. For 
rescreening all Screening assessments must be performed in accordance with the protocol 
(including QuantiFERON® TB-Gold In-Tube test), except for the chest X-Ray or TB work-up, 
if applicable, if performed within 12 weeks prior to Baseline.
5.5.2
Dispensing the investigational treatment 
Each study center will be supplied by Novartis with study drug in packaging of identical 
appearance. The study drug packaging has a 2-part label. Investigator staff will select the 
study drug to dispense to the patient using the medication kit number as provided by the IRT 
system on the label of the study drug kit. 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.
After Week 24, once the home study drug administration applies, patients will be expected to 
perform home drug administrations at the protocol-specified timepoints. For these cases, the 
Investigator will dispense, supported by IRT, an appropriate number of investigational
treatment packages for home administrations and detach the outer part of the label from the 
packaging as indicated above. The patients will record details including the date of 
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the study center. Patients will be asked to return all unused medication and packaging at each 
scheduled study visit.
Study center staff will record in the appropriate documents the dates of the administration.
5.5.3
Handling of study drug
The study drug must be received by designated personnel at the study center, handled and 
stored safely and properly, and kept in a secured location to which only these designated 
personnel have access. Upon receipt, all study drugs should be stored according to the 
instructions specified on the labels. Clinical supplies are to be dispensed only in accordance 
with the protocol. Technical complaints are to be reported to the respective Novartis Country 
Pharma Organization Quality Assurance.
The study drug must be stored in a refrigerator from 2 to 8°C (36 to 46°F) with restricted 
access to designated personnel, and must be carefully controlled in accordance with 
regulations governing investigational medicinal products and local regulations. The study 
drug should be protected from the light and must not be frozen.
Medication labels will be in the local language and comply with the legal requirements of 
each country. They will include storage conditions for the study drug but no information 
about the patient except for the medication number.
A pharmacist, Investigator or other qualified study center personnel must maintain an accurate 
record of the shipment and dispensing of study drug in a drug accountability log that will be 
kept in a secured location to which no blinded site staff (ie, blinded assessor for PASI and 
IGA mod 2011) would have access to. Monitoring of drug accountability will be performed 
by a field monitor performing site visits and done at the completion of the study. 
At the conclusion of the study, and as appropriate during the course of the study, the 
Investigator will return all unused study drug, packaging, drug labels, and a copy of the 
completed drug accountability log to the Novartis monitor or to the Novartis address provided 
in the Investigator folder at each site.
Patients will be asked to return all unused study drug and packaging at every study visit. A 
final reconciliation will be done by the site for the last study visit. Details for handling the 
home study drug administration will be provided separately.
 

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5.5.4
Instructions for prescribing and taking study drug
Secukinumab will be self-administered by patients during the study after the study 
assessments (including completion of PROs) and scheduled blood samples have been 
performed. 
For Treatment Period 1, all patients will be assigned to the same study drug regimen 
(300 mg secukinumab s.c. every week for the first 4 weeks, and thereafter every 4 weeks) and 
will self-administer the study drug at the study site under the supervision and guidance of site 
personnel at the time-points indicated in Table 5-1. To allow for comparable treatment group 
data on fixed study visits, patients will be trained for home drug administration prior to 
Treatment Period 2. If needed, a caregiver can be trained for home administration to provide 
support to the patient; corresponding training should be documented in the source data at the 
study center.
For Treatment Period 2, patients will be assigned to 4 different treatment interval groups 
depending on their PASI response at Week 24. Patients will self-administer their first dose of 
randomized study drug at Week 24 at the study site under the supervision and guidance of site 
personnel. Thereafter, patients will self-administer the study drug at either the study site or at 
home depending on the scheduled study drug administration by study group in Table 5-1 and
Table 6-2. 
Table 5-1
Timing of study drug administration by study group
Treatment Period 1
(Self-administration at Study Site)
(Self-administration at Home)
All Patients
All patients 
Baseline and
Weeks 1, 2, 3, 4, 8, 12, 16 and 20
None
Treatment Period 2
(Self-administration at Study Site)
(Self-administration at Home)
Patients with PASI ≥ 90
Group 1 (every 4 weeks)
Week 24, 28, 32, 36, 40, 44 and 48
None
Group 2 (every 6 weeks)
Week 24, 36, 48
Week 30, 42
Patients with 75 ≤ PASI < 90
Group 3 (every 4 weeks)
Week 24, 28, 32, 36, 40, 44 and 48
None
Group 4 (every 2 weeks)
Week 24, 28, 32, 36, 40, 44 and 48
Week 26, 30, 34, 38, 42 and 46
Study drug will be dispensed and self-administered with the support of qualified personnel 
during office visits in accordance with local laws and regulations or self-administered at home. 
The blinded assessor for PASI and IGA mod 2011 must not be part of the study drug 
dispensing or administration process. 
The first administration of secukinumab by qualified site personnel will occur at the Baseline
visit (Visit 2) after all study scheduled assessments have been performed (and 
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collected (pre-dose sample), if applicable. All study drug kits assigned to the patient during
the study will be recorded in the IRT.
All dates of injections administered to the patient during the study must be recorded on 
appropriate eCRF pages for dosage administration.
All injections administered at the study center should be documented in the source documents 
for drug handling; patient’s home administrations should also be documented.
The Investigator should promote compliance by instructing the patient to attend visits and 
perform home drug administration as planned so the study drug can be administered 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 attend a study visit as scheduled. 
5.5.5
Permitted dose adjustments and interruptions of study drug
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.
If a dose of secukinumab was dispensed by the IRT but not administered to a patient, this 
deviation event must be recorded in the eCRF.
5.5.6
Rescue medication
Use of rescue medication is not permitted during the study. 
Patients who do not respond, ie non responders (defined by a PASI < 50 response), or achieve 
only partial response, ie partial responders (defined by a PASI < 75 response) to the study 
drug until Week 24 will be withdrawn from the study. This allows for different treatment 
options outside of the study.
Pooled data from Phase 3 studies shows that 87.6 % of biologic-naïve patients achieved at 
least the PASI 75 criterion at Week 24 and can therefore be regarded as treatment responders.
5.5.7
Concomitant treatment
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 concomitant medications eCRF or the procedures and significant non-drug 
therapies eCRF. The start date, end date, dose, unit, frequency, route and reason for 
administration or change are to be recorded. 
In addition, psoriasis treatments used from the time the patient started to treat psoriasis will be 
reported on the prior psoriasis therapy eCRF. All topical treatments, systemic treatments and 
phototherapies for psoriasis administered prior to Day 1 (Baseline Visit) will be entered in the 
prior psoriasis therapy eCRF page (Section 6.2.2).
The Investigator/qualified site staff should instruct the patient to notify the study site 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 listed on the appropriate 
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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.
Mild to moderate topical corticosteroids (TCS) will be allowed, only if:

medication was used for an indication other than psoriasis and not on the area 
affected with psoriasis.

medication was used for up to 7 consecutive calendar days which includes the first day or 
less.
Higher than moderate TCS are not allowed from the Week 24 visit (post-dose) to Week 52.
To determine the potency of a TCS regimen, the Investigator/qualified site staff should take 
into account the potency of the topical steroid, active ingredient, its concentration, base, place 
of administration, the condition of the patient’s skin, and the frequency of administration. 
Use of these TCS must be recorded in the eCRF.
There is no restriction on the use of anti-histamines or of corticosteroid drops 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 medication for psoriasis in all body regions 
is restricted to bland emollients (not supplied by Novartis) and other non-medicated 
interventions (not listed in Table 5-2). Use of bland emollients must be recorded on the 
concomitant medications eCRF. Use of any other non-medicated interventions must be 
recorded in the eCRF.
The definition of bland excludes all topical medications that contain pharmacologically active 
ingredients such as (but not limited to) lactic acid, salicylic acid, urea, α-hydroxy acids or fruit 
acids.
Once the patient is screened and if the patient has intolerable scaling and/or itching, the use of 
bland emollients is permitted. The use of bland emollients should be avoided during the 
12 hours preceding a scheduled study visit. 
A mild to moderate potency TCS will be allowed for the treatment of the face, scalp, and 
genitoanal area during the Screening period. These TCS must be stopped the day before Day 1 
(Baseline Visit). 
Use of these TCS will be recorded on the prior psoriasis therapy eCRF if TCS was used for 
psoriasis or under Concomitant medications eCRF if TCS was used for any other reason.
5.5.7.3
Permitted concomitant medications for psoriatic arthritis
The use of non-steroidal anti-inflammatory drugs (NSAIDs), analgesic treatments or any other 
treatment given to treat psoriatic arthritis will be permitted only if not listed in
Table 5-2.
Use of these medications must be recorded on the appropriate eCRF page.
 

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Dose adjustments of these medications should be avoided during the study. If a dose 
adjustment of these medications should occur, they must be recorded in the eCRF.
5.5.8
Prohibited Treatment 
Use of any treatments displayed in Table 5-2 that could confound the efficacy of secukinumab 
will NOT be allowed during the study for any indication and washout 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 site staff must instruct 
the patient to notify them about any new treatments he/she 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 treatment listed in Table 5-2 was used during the study, the patient must 
discontinue use of the prohibited treatment if he/she wishes to continue in the study. At the 
discretion of the Investigator/qualified site staff, if the patient’s use during the study of a 
prohibited treatment listed in Table 5-2 presents undue safety risk for the patient, the patient 
should be discontinued from study drug as per Section 5.5.10. 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 treatment
Prior Therapy (before Baseline Visit [Day 1])
Prohibited treatments†, ‡ 
Washout period 
(before Baseline Visit 
[Day 1])
Ustekinumab, Guselkinumab
No prior use allowed
Secukinumab
No prior use allowed
Any biologic drug directly targeting IL-17 or the IL-17RA (other than 
secukinumab)
No prior use allowed
Alefacept, efalizumab
No prior use allowed
Biological immunomodulating agents other than above 
(eg, etanercept, adalimumab, infliximab)
No prior use allowed
Other new systemic treatments, eg apremilast 
No prior use allowed
Any biologic drug against psoriasis or against any other indication
No prior use allowed
Other systemic immunomodulating treatments§
(eg, methotrexate, cyclosporine A, corticosteroids (oral, i.v., 
intramuscular, s.c., intra-articular, transdermal)§, cyclophosphamide)
4 weeks
Other systemic psoriasis treatments (eg, retinoid, fumarates)
4 weeks
Photo chemotherapy (eg, PUVA) 
4 weeks
Phototherapy (eg, UVA, UVB) 
2 weeks
Topical treatment that is likely to impact signs and symptoms of 
psoriasis (eg, vitamin D analogues, pimecrolimus, retinoids, 
salicylvaseline, salicylic acid, lactic acid, tacrolimus, tar, urea, 
-hydroxy or fruit acids)
2 weeks
Live virus vaccinations
6 weeks
Any investigational treatment or participation in any interventional trial
4 weeks or 5 half-lives 
(whichever is longer)
Prohibited regimen of Topical Corticosteroids (TCS)
TCS higher than moderate potency on any body location
2 weeks
TCS mild to moderate potency on any body location other than the 
face, scalp and/or genitoanal area
2 weeks
TCS mild to moderate potency on the face, scalp and/or genitoanal 
area
1 day*
 

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Prior Therapy (before Baseline Visit)
Stable period
(before Baseline Visit [Day 
1])
Any other treatment known to worsen psoriasis (eg, beta-blockers, 
calcium channel blockers, lithium)
Stable at least 4 weeks 
before Baseline Visit (Day 1)
Concomitant therapy (after Baseline Visit [Day 1])
Prohibited regimen of Topical Corticosteroids (TCS)
Prohibited period
TCS any potency
Baseline Visit (Day 1) to 
Week 24 visit (pre-dose)**
TCS any potency on area affected with psoriasis
Week 24 visit (post-dose) to 
Week 52 visit
TCS higher than moderate potency 
Week 24 visit (post-dose) to 
Week 52 visit
TCS mild to moderate potency used for more than 7 consecutive days 
Week 24 visit (post-dose) to 
Week 52 visit
† 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 study drug at the discretion 
of the Investigator/qualified site staff. If the patient received a live virus vaccination during the study, 
the patient must discontinue study drug.
§ Inhalative CS with only a topical effect (eg, to treat asthma) are not considered “systemic
immunomodulating treatments” and are therefore acceptable as comedication. 
* Mild to moderate TCS used on the face, scalp and/or genitoanal area must be stopped at the latest 
on the day prior to the Baseline Visit (Day 1).
** No TCS is allowed during Treatment Period 1 (from Baseline Visit [Day 1] to Week 24 visit pre-dose).
5.5.9
Exposure to light
Patients need to be advised to limit exposure to UV light (including sunbathing and/or use of 
UV tanning devices) during the study to avoid possible effect on psoriasis.
5.5.10
Discontinuation of study drug
Patients may voluntarily discontinue study drug for any reason at any time. 
The Investigator/qualified site staff should discontinue study drug for a given patient if, on 
balance, he/she believes that continuation would be detrimental to the patient’s well-being.
If discontinuation occurs for any reason in a treatment period, the Investigator/qualified site 
staff must make every effort to determine the primary reason for a patient’s discontinuation 
from the study drug. This information will then be recorded in the eCRF.
Study drug must be discontinued under the following circumstances: 

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 study drug (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 
study drug. 

Pregnancy (see Section 6.5.6 and Section 7.4). 
 

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
Use of prohibited treatment as per recommendations in Section 5.5.8. 
Patients discontinued from study drug will NOT be considered discontinued from the study. 
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 24 (for early discontinuation during Treatment Period 1) or the end of treatment 
period 2 (EOT2) visit/Week 52 (for early discontinuation during Treatment Period 2) should 
be completed at this visit. The patient will then return per appropriate schedule for visit Week 
60, if applicable.
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 24) or EOT2 visit (Week 52) assessments, respectively. The 
patient will then return per appropriate schedule for the Week 60 visit, if applicable.
The Investigator/qualified site staff must contact the IRT when the patient completes the 
EOT1 visit (Week 24) or EOT2 visit (Week 52) assessments to register the patient’s early 
completion of the study due to study drug discontinuation. See Section 6 for the required 
assessments of these patients after study drug discontinuation.
5.5.11
Discontinuation from a treatment-free period
If discontinuation occurs for any reason in the treatment-free follow-up period, the 
Investigator/qualified site staff must make every effort to determine the primary reason for a 
patient’s premature withdrawal from the study. This information will then be recorded by 
Investigator/qualified site staff on the applicable section of the eCRF. 
See Section 6 for the required assessments of those patients who discontinue from the 
follow-up period.
5.5.12
Withdrawal of 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 and does not want any further visits or assessments and 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 (eg, 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 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.
5.5.13
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 
 

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patient, family or family physician as agreed in the informed consent and by documenting in 
the source documents steps taken to contact the patient, eg 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 would have occurred.
5.5.14
Emergency breaking of assigned treatment code 
Not applicable.
5.5.15
Study completion and post-study drug
Study completion is defined as all patients who have been enrolled and completed the study as 
per 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.
If there is the possibility that patients can participate in an extension study the eligibility 
criteria and all study details should be explained in a corresponding study protocol.
5.5.16
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 5.5.10. 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 
Board/Independent Ethics Committee (IRB/IEC) of the early termination of the study.
6
Visit schedule and assessments
Table 6-1 lists all of the assessments and indicates with an “X” when the visits are performed. 
An ‘S’ indicates the data for that assessment are in the source documents at the site. 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). Every effort should be 
made to respect the timeframe for all visits. 
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 site staff will 
record if the patient was rescreened on the eCRF 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 eCRF to correspond to 
the new Screening Patient Number. Informed consent for a 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 
 

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with the protocol, except for the chest X-ray or TB work-up, if applicable, if performed not 
more than 12 weeks prior to Day 1 (Baseline). If patients do not have a chest X-ray available 
within 12 weeks of the projected Day 1 date, the X-ray should be performed after it is certain 
the patient meets inclusion/exclusion criteria in order to minimize unnecessary exposure to 
radiation.
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 performed by the central 
laboratory. 
During the Treatment Periods 1 and 2, patients may be seen at an unscheduled visit, eg, if they 
experience deterioration of psoriasis or suspected AEs. During these unscheduled visits, study 
drug will NOT be administered.
Recommended visit windows
Treatment periods:

± 2 days for Baseline, Week 1, Week 2, Week 3 and Week 4 and for Week 24.

± 2 days for all study drug home administrations.

± 5 days for all other study visits.

Visit 1 and Visit 2 must not be conducted at the same day and all relevant information for 
Visit 2 must be available before treating the patient. The screening period might not be 
longer than 4 weeks.
For patients who discontinue study drug prematurely before the end of the Treatment Period 1 
for any reason other than withdrawal of informed consent, the Week 24 (planned EOT1) visit 
must be performed at least 28 days (4 weeks) after the last drug administration and the patient 
should then enter the treatment free follow-up period, if applicable.
For patients who discontinue study drug prematurely before the end of the Treatment Period 2 
for any reason other than withdrawal of informed consent, the Week 52 (planned EOT2) visit 
must be performed at least 28 days (4 weeks) after the last drug administration and the patient 
should then enter the treatment free follow-up period, if applicable.
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 (ie, certified letter) immediately. At this contact, the safety (eg, potential 
occurrence of AEs or SAEs) and the primary reason for the patient’s premature withdrawal 
should be determined. Documentation of attempts to contact the patient should be recorded in 
the patient source documents.
For Group 3 and Group 4 at a minimum, patients will be contacted for safety evaluations 
during the 12 weeks following the last dose of study drug, including final contact at the 
12-week point 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’s record.
Recommended order of assessments:
The recommended order of PRO assessment for completion by the patient is as follows: 

DLQI

Patient’s assessment of pain, itching and scaling
 

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
EQ-5D© Health Status Questionnaire

WPAI-PSO
The recommended order of efficacy and other assessments, which will be completed by the 
Investigator/qualified site staff, is as follows:

IGA mod 2011 assessments (performed by the blinded assessor)

PASI assessments (performed by the blinded assessor)

Review PRO data (at applicable visits).

Physical examination (at applicable visits).

All remaining study visit procedures (eg vital signs measurements) are to be completed 
prior to study drug dosing

Safety blood samples and PK blood sample will be collected

Contact IRT to register the patient visit and enter all data as applicable.

Self-administration of study medication. Note: if needed, a caregiver of the patient can be 
trained for home administration to provide support to the patient; corresponding training 
should be documented in the source data at the study center (see Section 5.5.4).
 

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Table 6-1
Assessment schedule
Period
Scr
Treatment Period 1
Treatment Period 2
FU
Unscheduled Visitd
Comments
Visit 
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Week
-4 
to 
BL e
BL
1
2
3
4
8
12
16
20
24
a, b
28
32
36
40
44
48
52
c
60
Recommended visit 
window (days)
±2
±2
±2
±2
±5
±5
±5
±5
±2
±5
±5
±5
±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
Psoriasis: medical 
history / previous 
psoriasis therapies
X
Other medical history 
and prior medications
X
Concomitant 
medications
X
X
X
X
X
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
S
S
S
S
S
Height
X
X
Weight
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory sampling: 
safety panel
(Clinical chemistry
including urine, 
hematology)
X
X
X
X
X
X
X
X
X
X
X
X
For processing of 
samples please refer to 
the manual of the central 
lab.
 

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Period
Scr
Treatment Period 1
Treatment Period 2
FU
Unscheduled Visitd
Comments
Visit 
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Week
-4 
to 
BL e
BL
1
2
3
4
8
12
16
20
24
a, b
28
32
36
40
44
48
52
c
60
Recommended visit 
window (days)
±2
±2
±2
±2
±5
±5
±5
±5
±2
±5
±5
±5
±5
±5
±5
±5
±5
Chest X-ray 
(or CT/MRI)
S
S
Where a patient has not 
had a chest X-ray, chest 
CT or chest MRI, CT 
performed within 3 
months prior to 
Screening, an image 
should be obtained once it 
is clear that the patient 
meets the other 
inclusion/exclusion criteria 
in order to minimize 
unnecessary exposure X-
ray radiation.
QuantiFERON® 
TB-Gold In-tube teste
X
X
see lab manual
Serum pregnancy 
test
X
X
Only for females of child-
bearing potential.
Urine pregnancy test 
(local)
X
X
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. 
ECG 
(standard 12-lead)
X
X
X
X
X
PASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BSA
X
X
X
X
 

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Period
Scr
Treatment Period 1
Treatment Period 2
FU
Unscheduled Visitd
Comments
Visit 
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Week
-4 
to 
BL e
BL
1
2
3
4
8
12
16
20
24
a, b
28
32
36
40
44
48
52
c
60
Recommended visit 
window (days)
±2
±2
±2
±2
±5
±5
±5
±5
±2
±5
±5
±5
±5
±5
±5
±5
±5
IGA mod 2011
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
WPAI-PSO
X
X
X
X
X
X
X
X
Assessment of pain, 
itching and scaling
X
X
X
X
X
X
X
X
EQ-5D©
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
X
X
X
X
X
Assessment of 
rebound
X
Unscheduled rebound 
assessment only to be 
done at an unscheduled 
visit that occurs during the 
post-treatment follow-up 
period.
Randomization by 
IRT
X
IRT contact such as 
for registration or 
drug supply including 
home administration 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK blood sample 
X
X
X
X
X
X
Samples will be shipped 
by the sites and stored by 
the central laboratory. 
Samples will be shipped 
to reference laboratories 
for analysis. Samples 
need to be taken before 
dosing.
 

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Period
Scr
Treatment Period 1
Treatment Period 2
FU
Unscheduled Visitd
Comments
Visit 
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Week
-4 
to 
BL e
BL
1
2
3
4
8
12
16
20
24
a, b
28
32
36
40
44
48
52
c
60
Recommended visit 
window (days)
±2
±2
±2
±2
±5
±5
±5
±5
±2
±5
±5
±5
±5
±5
±5
±5
±5
Check self-
administration log
S
S
S
S
S
S
S
S
Patients must return the 
self-administration 
log 
along with all dispensed 
PFS and drug packaging 
at every visit, if applicable.
Complete Screening
period eCRF
X
Complete end of 
Treatment Period 1 
eCRF
X
Complete end of 
Treatment Period 2 
eCRF
X
Footnotes:
a Visit 11, patients will have the last assessment for Treatment Period 1 performed prior to administration of study drug. 
b Visit 11 assessments must be completed for patients who discontinue study drug prematurely during Treatment Period 1; patient should then enter the 
post treatment follow-up period, if applicable. 
c Visit 18 assessments must be completed for patients who discontinue treatment prematurely during Treatment Period 2. 
d Unscheduled visit – assessments at discretion of the Investigator.
e A repeat QuantiFERON® TB-Gold In-Tube test is recommended if the result of the first QuantiFERON® TB-Gold In-Tube test is “indeterminate”. The 
patient must be referred for a follow-up TB work-up (as per local guidelines) if either the first or the repeat test is “positive” or if the results of both tests are 
“indeterminate”. If the first test is indeterminate, the Investigator may decide not to repeat the test and to proceed directly to the work-up, though this is not 
recommended. 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.
 

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Abbreviations:
AE: adverse event; BL: baseline; CT: computer tomography; DLQI: Dermatology Life Quality Index; ECG: electrocardiogram; eCRF: electronic case report form; 
EOT: end of treatment; EQ-5D©: EuroQOL 5-Dimension Health Questionnaire; FU: follow-up; IGA: Investigator’s Global Assessment; IRT: interactive response technology; 
MRI: magnetic resonance imaging; PASI: Psoriasis Area and Severity Index; PFS: pre-filled syringe; PK: pharmacokinetic; S = assessment to be recorded on source 
documentation Scr: screening; TB: tuberculosis; Uns: unscheduled visit; WPAI-PSO: Work Productivity and Activity Impairment Questionnaire-Psoriasis; 
X = assessment to be recorded on clinical database
Table 6-2
Overview of study drug administration for Treatment Period 2
Visit 
11
12
13
14
15
16
17
18
Week
24
26
28
30
32
34
36
38
40
42
44
46
48
52
Recommended 
visit window 
(days)
±2
±2
±5
±2
±5
±2
±5
±2
±5
±2
±5
±2
±5
±5
Study drug 
administration 
Group 1
S
S
S
S
S
S
S
Group 2
S
H
S
H
S
Group 3
S
S
S
S
S
S
S
Group 4
S
H
S
H
S
H
S
H
S
H
S
H
S
Abbreviations: H = home administration; S = administration at study center
 

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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 Screening Phase 
Disposition eCRF. 
The Screening Visit date, the Demography eCRF, the Informed Consent eCRF, the 
Inclusion/Exclusion eCRF, and the Patient Rescreening eCRF must be completed. The AE 
eCRF should be completed for any AEs that occurred during the Screening period. The 
withdrawal of consent eCRF must be completed if consent was withdrawn during the 
Screening period. The Death eCRF should be completed in the case of a 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.
Investigators will have the discretion to record abnormal test findings on the medical history 
eCRF whenever in their judgment, the test abnormality occurred prior to the informed consent 
signature.
If a patient discontinues the study prior to entering the randomized, assessment-blinded 
treatment period (Treatment Period 2), the IRT should be notified and the reason for not being 
randomized (at Week 24) will be entered in the eCRF. The patient should be seen as soon as 
possible and treated as a discontinued patient as described in Section 5.5.10.
6.2
Patient demographics/other baseline characteristics 
All Baseline assessments should be performed prior to first study drug administration. Please 
refer to Table 6-1. 
6.2.1
Demographics
Patient demographic and Baseline characteristic data will be collected at the Screening Visit. 
Data to be collected on all patients include: date of birth (if allowed by local data privacy 
rules), age, sex, race, as well as height and weight. 
6.2.2
Psoriasis medical history / previous psoriasis therapies 
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:

The date of first diagnosis of chronic plaque psoriasis (by a physician).

The previous treatments of psoriasis (including previous use of non-biologic systemic 
therapies, as well as phototherapy and/or photo chemotherapy) and the reason for 
discontinuation of each therapy.

The presence of psoriatic arthritis and the date of first diagnosis (by a physician).
 

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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 signing of 
informed consent should be reported as cardiovascular history. Cardiovascular risk factors 
will also be recorded.
6.2.5
Relevant medical history / current medical conditions
Relevant medical history and current medical conditions, not including psoriasis or psoriatic 
arthritis, prior to signing of the informed consent 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.
6.2.5.1
Chest X-Ray
A chest X-ray, CT scan, or MRI obtained within 12 weeks prior to enrollment will be used to 
determine eligibility. If patients do not have a chest X-ray, CT scan, MRI available within 
12 weeks prior to enrollment, a chest X-ray (or chest MRI at pre-specified sites) only must be 
done after it is fairly certain the patient meets the other inclusion/exclusion criteria in order to 
minimize unnecessary exposure to X-ray radiation for patients.
If the chest X-ray, CT scan, or MRI evaluated by a qualified physician shows evidence of 
ongoing infection or malignancy and the patient was not treated subsequent to the X-ray 
(CT scan or MRI), the patient will not be eligible to enter the study.
6.2.6
Prior and concomitant medications 
Concomitant medications and prior medications taken over the 6 months preceding the study 
Screening Visit (Visit 1) will be captured in the eCRF and any other relevant medication 
taken before 6 months at the discretion of the Investigator. 
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 (QuantiFERON-TB Gold assay).
Any significant findings will be recorded in the TB Assessment eCRF and the Medical 
History eCRF, as necessary.
 

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6.2.7.1
QuantiFERON TB-Gold In-Tube assay
A QuantiFERON® TB-Gold In-Tube assay 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 and Kumar 2008). The QuantiFERON®-TB Gold assay test 
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 Investigators in the laboratory 
manual. 

If the test result is negative, the patient may be enrolled.

If the test result is positive, the Investigator should perform work-up for the test result as 
per local procedures. If a TB work-up was conducted prior to the Screening of the patient, 
results of the work-up can be used to assess eligibility if the work-up was conducted 
within 12 weeks prior to Baseline:
o
Patients who are positive for latent TB per work-up 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 work-up are not eligible for the study.
o
Patients who are negative for TB (no signs of latent or active TB) per work-up 
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 
work-up (this is however not recommended). If a TB work-up was conducted prior to 
Screening the patient, results of the work-up can be used to assess eligibility if the 
work-up 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 
work-up as per local guidelines. The patient will not be eligible for enrollment if:
o
“active TB is present” or 
o
“latent TB is present” and is untreated as per local guidelines. 
Patients negative for TB per work-up (no signs of latent or active TB) may be 
enrolled into the study if the work-up was conducted within 12 weeks prior to 
Day 1 (Baseline Visit).

If eligibility is being assessed with only one test result and a TB work-up (ie, 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 TB work-up will only be considered if it was completed within 
12 weeks prior to Baseline. Patients who are positive for latent TB per work-up may be 
enrolled to the study if sufficient treatment has been initiated according to local routine 
 

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clinical practice and will be maintained for the prescribed duration. Patients positive for 
active TB per work-up are not eligible for the study. Patients negative for TB per work-up 
(no signs of latent or active TB) may be enrolled to the study.
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 work-up 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 work-up per local guidelines (if no work-up 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 include (all laboratory tests are 
performed centrally except where indicated; see also Table 6-1) the following:

12-lead ECG, vital signs, hematology, clinical chemistry, physical examination, height, 
weight, past medical history record of HIV, Hepatitis B or C status, DLQI©, WPAI-
PSO, Patient’s assessment of pain, itching and scaling, EQ-5D©, as well as 
assessments of PASI, BSA and IGA mod 2011 and PK, if applicable. A serum 
pregnancy test will be performed for women of child-bearing potential. 
6.3
Treatment exposure and compliance 
All doses of study drug administered will be recorded on the appropriate Dosage 
Administration Record eCRF page. Patient compliance to the study drug should be assessed 
by qualified site 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 medication at every visit back to the investigational site for a compliance 
check. 
6.4
Efficacy
All efficacy assessments should be performed prior to the administration of study drug.
Efficacy assessments
The efficacy assessments are recommended to be completed in the following order by the 
blinded PASI assessor. In all cases, the assessor will be blind to treatment allocation. Please 
refer to Section 5.4. 

IGA mod 2011

PASI
All remaining study visit procedures (eg laboratory sample collection, vital signs 
measurements, PK sample, if applicable) are recommended to be completed prior to 
administration of study drug.
Patient-reported outcomes 
Patient reported outcomes are recommended to be performed in the following order, prior to 
any Investigator assessments:

DLQI©

Patient’s assessment of pain, itching and scaling

EQ-5D© 

WPAI-PSO
 

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6.4.1
Investigator’s Global Assessment Modified 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 (ie, blinded 
assessor) conducts the assessment throughout the study wherever possible. 
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 the
patient achieves 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 rating scale for overall psoriatic disease is shown in Table 6-3.
The IGA mod 2011 used in this study is static, ie, 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 score will be recorded in the eCRF.
Table 6-3
Investigator global assessment modified 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 total body surface area and psoriasis area and severity 
index 
The blinded PASI assessor will complete the PASI assessment as indicated in Table 6-1. 
Whenever possible, the same blinded PASI assessor 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 up to 
estimate the total BSA affected by chronic plaque psoriasis. 
The PASI scoring system is further described in Table 6-4.
 

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A PASI score (Fredriksson and Pettersson 1978; Weisman et al 2003; Gottlieb et al 2005) 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 the PASI is collected at Day 1 (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.
 

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Table 6-4
Psoriasis area and severity index 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
 

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6.4.3
Definitions of efficacy variables based on psoriasis area and severity 
index
The following definitions will be used in this study based on the Committee for Medicinal 
Products for Human Use (CHMP) guidelines for 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.

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).
6.4.3.1
Definitions of relapse and rebound
For plaque psoriasis, in addition to the assessment of PASI, the Investigator will assess 
whether new pustular psoriasis, new erythrodermic psoriasis, or more inflammatory psoriasis 
has occurred (yes/no).

Relapse: when the achieved maximal PASI improvement from Baseline is reduced 
by >50% (CHMP/EWP/2454/02 corr).

Rebound: A patient will be considered to have experienced a rebound, if PASI increases 
to ≥125% of Baseline PASI, or if new pustular psoriasis, new erythrodermic psoriasis, or 
more inflammatory psoriasis occurs within 8 weeks after the last dose of study drug has 
been received (CHMP/EWP/2454/02 corr).
6.4.4
Appropriateness of efficacy assessments 
PASI scores outcome measures, the assessment of the severity of the psoriasis symptoms and 
the extent to which the patient’s body area is affected by the disease, is mandated by the EMA 
for the clinical investigation of medicinal products for the treatment of psoriasis
(CHMP/EWP/2454/02 corr).
As indicated in Section 6.4.1, the IGA mod 2011 scale has been developed by Novartis
(Langley et al 2013) in collaboration with health authorities, in particular the FDA and has 
been used extensively in the secukinumab in psoriasis Phase 3 program.
6.5
Safety 
From Day 1 (Baseline Visit), all blood draws and safety assessments must be performed prior 
to study drug administration. Appropriate safety assessments (eg, 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
 

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
Laboratory evaluations (hematology, clinical chemistry including urine samples)

12-Lead ECGs

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 site staff throughout the study.
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings that are present prior to the patient signing informed consent 
must be included in the Medical History screen on the patient’s eCRF. Significant findings 
made after the signing of the informed consent which meet the definition of an AE must be 
recorded on the AE screen of the patient’s eCRF (Section 7.1).
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 and diastolic blood pressure will be measured twice
(measurements separated by 1 to 2 minutes) using a validated device with an appropriately 
sized cuff and each BP measurement will be recorded in the source (Mancia et al 2007). In 
case the cuff sizes available are not large enough for the patient’s arm circumference, a 
sphygmomanometer with an appropriately sized cuff may be used. If possible, assessments 
should be performed by the same study site staff member throughout the study.
Normal blood pressure will be defined as a systolic pressure of 90 to < 120 mmHg, and a 
diastolic blood pressure of 60 to < 80 mmHg under the measurement conditions outlined 
above. Notable blood pressure will be hypertension (systolic blood pressure of ≥140 mmHg 
and/or diastolic blood pressure of ≥90 mmHg) or hypotension (systolic blood pressure of 
< 90 mmHg and/or a diastolic blood pressure of < 60 mmHg). A blood pressure indicative of 
prehypertension (systolic blood pressure of 120 to < 140 mmHg and/or diastolic blood 
pressure 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.
 

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6.5.3
Height and weight
Height and body weight will be measured as 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 site staff 
member and using the same scale throughout the study. 
6.5.4
Laboratory evaluations
Patients should avoid smoking within the hour preceding the blood draws.
A central laboratory will be used for analysis of all specimens unless noted otherwise. Details 
on the collections, shipment of samples and reporting of results by the central laboratory are 
provided to Investigators in the Laboratory Manual.
For the identification of notable values, the laboratory manual should be consulted.
Whether action needs to be taken to address notable laboratory values 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.
For clinically notable thresholds please refer to Appendix 1 or the lab manual.
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 
scheduled study visits, within the visit window, as specified in Table 6-1.
6.5.4.2
Clinical chemistry
Serum chemistry will include urea, creatinine, total bilirubin, alanine aminotransferase 
(ALT)/serum 
glutamic 
pyruvate 
transaminase 
(SGPT), 
aspartate 
aminotransferase 
(AST)/serum glutamic oxaloacetic transaminase (SGOT), gamma glutamyl transferase (GGT), 
alkaline phosphatase, sodium, potassium. Serum chemistry will be measured at scheduled 
study visits, within the visit window, as specified in Table 6-1.
For a local analysis of urine, dipsticks will be provided by the central laboratory to the sites 
for the assessment. Sites should record the results in the source documentation and report 
these in the eCRF for each patient, as specified in Table 6-1.
6.5.5
Electrocardiogram
A standard 12-lead ECG will be performed as indicated in the schedule of assessments (Table 
6-1). The Investigator/qualified site staff must review and initial the tracing. The tracing must 
then be stored with the patient's source documents.
If the ECG findings are clinically relevant and would prevent the patient from participating in 
the study (taking into account the patient's overall status as well as the medication profile), the 
 

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patient should be recorded as a screen failure, should NOT be enrolled and should not receive 
treatment. 
All ECGs will be independently reviewed by a central reader. Instructions for the collection 
and transmission of the ECGs to the independent reviewer will be provided in the ECG 
Investigator manual. Although there is no exclusion criterion specifically based on the ECG, 
the Baseline ECG performed at the Baseline Visit must be reviewed for major abnormalities
before dosing at the Baseline Visit.
6.5.6
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, study drug must be definitively discontinued, as described in
Section 5.5.10.
6.5.7
Appropriateness of safety measurements 
The safety assessments selected in this study are reliable and standard measures for a biologic 
immunomodulating agent in adult patients with psoriasis.
6.6
Other assessments

Health-related quality of life (HRQoL) assessments as shown in Table 6-1. 
6.6.1
Resource utilization
Not applicable.
6.6.2
Health-related Quality of Life
The impact of psoriasis on various aspects of patient’s HRQoL will be assessed by the 
following validated instruments, each of which will be performed as indicated in Table 6-1:

DLQI©

Patient’s Assessment of pain, itching and scaling

EQ-5D©

Work Productivity and Activity Impairment Questionnaire Psoriasis (WPAI-PSO)
All these quality of life assessments should be completed by the patient before the patient sees
the study physician (Investigator or designee) who will perform the Investigator assessments. 
All these quality of life 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 patient should be given sufficient space and time to complete the 
 

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questionnaires. The study coordinator should check the questionnaires for completeness and 
encourage the patient 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 instructions given in Section 7 of the protocol.
Investigators should not encourage patients to change the responses reported in the completed 
questionnaires.
6.6.2.1
Dermatology Life Quality Index 
The DLQI© is a 10-item general dermatology disability index designed to assess HRQoL 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 randomized controlled studies in 
dermatology. 
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 HRQoL 
impairment. Each subscale of the DLQI© may also be analyzed separately.
6.6.2.2
Patient’s Assessment of pain, itching and scaling
A self-administered, 11-point numeric rating scale (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 the 0 represents the absence or null end of the pain, itching, or scale 
intensity (ie, no pain, itching or scaling) and the 10 represents the other extreme of pain, 
itching, or scaling intensity (ie, pain, itching or scaling as bad as it could be). The number that 
the patient selects represents his or her intensity score.
6.6.2.3
EuroQOL 5-Dimension Health Status 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
 

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the instrument takes 1 to 2 minutes to complete. The instrument essentially consists of 2 pages 
– the EQ-5D© descriptive system and the EQ visual analogue scale. The EQ-5D© descriptive 
system comprises the following 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort 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 one 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 et al 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 labeled “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.
6.6.2.4
Work Productivity and Activity Impairment Questionnaire Psoriasis 
The WPAI-PSO version 2 is a self-administered questionnaire derived from the WPAI-
General Health (Reilly et al 1993), which comprises 6 questions regarding the effects of 
psoriasis on the patient’s ability to work and to perform regular activities and is based on their 
experiences in the previous 7 days. The questionnaire quantifies the number of hours that the 
respondent was unable to work and, using a 10-point scale, evaluates the extent to which the 
respondent’s psoriasis affected their productivity while working. For respondents who are not 
in paid employment, the questionnaire evaluates the extent to which the individual 
respondent’s psoriasis affects their ability to perform regular daily activities. 
6.6.3
Pharmacokinetics
At selected study sites, blood samples will be collected for PK at the scheduled visits as 
indicated in Table 6-1. All blood samples will be taken by direct venipuncture. Blood samples 
(approximately 2 mL, not less than 1.5 mL) will be collected into serum separating tubes. The 
blood sample will be allowed to clot for a minimum of 30 minutes at room temperature prior 
to harvesting of the serum. The serum will be obtained by centrifugation at approximately 
2500 rpm for 10 minutes. Serum samples will be placed on ice, split into 2 aliquots 
(polypropylene tubes) and then stored (within 30 minutes of serum collection by 
centrifugation) at -70°C to -20°C (approximately) prior to shipment to the central laboratory. 
Shipment of stored aliquots from the site to the central lab should be on a pre-specified basis. 
To the extent possible, the site should send each aliquot to the central laboratory separately. 
The central lab will ship one aliquot of the samples on dry ice to the analytical laboratory. The 
remaining aliquots must be kept at the central laboratory as a backup sample. Remaining 
samples will only be disposed of after approval by the Clinical Trial Team (typically 6 to 
12 months after the Clinical Study Report (CSR) is published).
The actual sample collection date and reference time point of collection will be entered in the 
eCRF, as appropriate. Sampling problems will be noted in the eCRF as well.
 

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For a detailed description of the complete PK blood sampling refer to the corresponding 
laboratory manual.
6.6.3.1
PK sample handling, labeling and shipment instructions
A laboratory manual will be provided with detailed information on sample collection, sample 
handling and shipment. Tubes and labels will be provided by the central laboratory with 
study/sample type and sample number preprinted on the label.
6.6.3.2
Pharmacokinetic sample stability
Secukinumab is stable in serum samples for up to 12 months at or below -15°C and for up to 
32 months at or below -70°C.
6.6.3.3
Pharmacokinetic analytical methods
An ELISA method will be used for bioanalytical analysis of secukinumab in serum with an
anticipated lower limit of quantification (LLOQ) of 80 ng/mL. A detailed description of the 
methods used to assess AIN457 concentration will be provided in the bioanalytical raw data 
for the study and the respective Bioanalytical Data Report.
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 should be explained in a corresponding separate study protocol.
7
Safety monitoring 
7.1
Adverse events
An AE is any untoward medical occurrence (ie, 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 investigational 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 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
eCRF.
The occurrence of AEs should be sought by non-directive questioning of the patient at each 
visit during the study. Adverse events also may be detected when they are volunteered by the 
patient during or between visits or through physical examination, laboratory test, or other 
assessments.
Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
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
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 patient with 
underlying disease. Investigators have the responsibility for managing the safety of individual 
patient and identifying AEs. Alert ranges for labs 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 (see Section 7.2.1).

Action taken with the study treatment.

Concomitant medication or therapies taken.

Outcome.
All AEs should be treated appropriately. Treatment may include one or more of the following: 
no action taken (ie, 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 the study drug, the interventions 
required to treat it, and the outcome.
Information about common side effects already known about the investigational drug can be 
found in the Investigator’s Brochure (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 
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7.2
Serious adverse events 
7.2.1
Definition of SAE 
A Serious Adverse Event (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, ie, 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 7.2.2. 
7.2.2
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, or 12 weeks after the
last study drug (if applicable), 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
 

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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). 
SAEs (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 and Epidemiology 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 Investigator’s Brochure or Package Insert 
(new occurrence) and is thought to be related to the study drug a Drug Safety and 
Epidemiology Department associate may urgently require further information from the 
Investigator for Health Authority reporting. Novartis may need to issue an Investigator 
Notification (IN) 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
Liver safety monitoring 
To ensure patient safety and enhance reliability in determining the hepatotoxic potential of an 
investigational drug, a standardized process for identification, monitoring and evaluation of 
liver events has to be followed. 
Liver events are divided into 2 categories:

Liver events of special interest which consist of elevated transaminases and/or alkaline 
phosphatase and/or total bilirubin (elevated liver function tests [LFTs])

Medically significant liver events which are considered as SAEs and which consist of 
marked elevations of LFTs and / or pre-specified AEs
Please refer to Table 14-1 in Appendix 2 for complete definitions of liver events. 
Any liver event which meets the criteria for “medically significant” event as outlined in 
Table 14-1 of Appendix 2 should follow the standard procedures for SAE reporting as 
described in Section 7.2. 
Every liver event as defined in Table 14-1 of Appendix 2 should be followed up by the 
Investigator/qualified site staff as summarized below. Detailed information is outlined for 
liver laboratory trigger in Table 14-2 in Appendix 2.

Repeating the LFT to confirm elevation as appropriate

Discontinuation of the investigational drug if appropriate

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
A causality assessment of the liver event via exclusion of alternative causes (eg, disease, 
co-medications)

An investigation of the liver event which needs to be followed until resolution 
These investigations can include serology tests, imaging and pathology assessments, and 
hepatologist’s consultancy, based on Investigator/qualified site staff’s discretion. 
All follow-up information, and the procedures performed, should be recorded on appropriate 
eCRF pages.
7.4
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 site staff to the local Novartis Drug Safety and Epidemiology 
Department. Pregnancy 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 site 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 site regularly to check the completeness of 
patient records, the accuracy of entries in the eCRFs, the adherence to the protocol and to 
Good Clinical Practice (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 site 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 and 
ensure that only unblinded personnel would have access to. 
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, ECGs, and the results of any other tests or assessments. All 
information on eCRFs 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 
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The Investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the eCRF 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 eCRFs 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 unblinded Investigator staff will enter the data required by the protocol into the 
eCRF system. Designated Investigator study center staff will not be given access to the 
system until they have been trained. 
The blinded assessor for the PASI and IGA mod 2011 assessment will report data in a 
separate database. The blinded assessor must not have access to details that could compromise 
the blinding. 
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 investigational study 
center. 
8.3
Database management and quality control 
Novartis staff or designated CRO staff review the data entered into the eCRFs by 
Investigator/qualified study center staff for completeness and accuracy and instruct the 
Investigator/qualified study center staff to make any required corrections or additions. Queries 
are sent to the investigational study center
using an electronic data query. 
Investigator/qualified study center staff is 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. Investigator/qualified study center staff will complete and sign the 
faxed copy and fax it back to Novartis staff that will make the correction to the database. The 
signed copy of the Data Query Form is kept at the study center.
Concomitant medications entered into the database will be coded using the World Health 
Organization 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). All ECGs will be independently reviewed by a central reader. 
Instructions for the collection and transmission of the ECGs to the independent reviewer will
be provided in the ECG Investigator manual.
The blinded assessors for PASI and IGA mod 2011 assessments will use electronic devices to 
report PASI and IGA mod 2011 data. These data will be collected centrally and the results 
 

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will be sent electronically to Novartis (or a designated CRO). In case electronic devices 
cannot be used a paper-based process is acceptable and details of the whole process are 
described in a separate user manual.
Randomization codes, data about all study drug dispensed to the patient and some efficacy 
data will be tracked using IRT. The system will be supplied by Novartis staff or a vendor that 
will also manage the database. The database will be sent electronically to Novartis (or a 
designated CRO). Details are provided in a user manual.
8.4
Data Monitoring Committee
In alignment with the EMA Guideline on Data Monitoring Committees
(DMCs)
(EMEA/CHMP/EWP/5872/03 Corr) no DMC is deemed to be required for this Phase 3b 
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. Furthermore, the study population is not considered to have an 
elevated risk of more severe outcomes during this study, which is also in accordance with US, 
Department of Health and Human Services FDA guidelines (Guidance for Clinical Trial 
Sponsors. Establishment and Operation of Clinical Trial Data Monitoring Committees, 2006). 
8.5
Adjudication Committee
Not applicable.
9
Data analysis 
For the analysis of Treatment Period 1 (until/including Week 24) all patients will receive the 
same treatment:

secukinumab 300 mg s.c. every 4 weeks
For the analysis of Treatment Period 2 (maintenance period Week 24 to Week 52) the 
following treatment groups are utilized.
Only patients with at least a 90% reduction in PASI score from Baseline will be randomized 
at Week 24 on a 1:1 basis to either Group 1 or Group 2:

Group 1 (recommended maintenance treatment): secukinumab 300 mg s.c. every 4 weeks.

Group 2 (experimental maintenance treatment): secukinumab 300 mg s.c. every 6 weeks.
Patients who did not achieve a PASI 90 at Week 24 but achieved at least a PASI 75 response 
are eligible for dose frequency intensification and will be randomized to either Group 3 or 
Group 4:

Group 3 (recommended maintenance treatment): secukinumab s.c. 300 mg every 4 weeks.

Group 4 (experimental maintenance treatment): secukinumab s.c. 300 mg every 2 weeks.
Patients with less than a 75% reduction in PASI score from Baseline at Week 24 are not 
eligible for randomization and will be discontinued from the study.
 

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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 two-sided CIs 
will be displayed.
9.1
Analysis sets 
The Safety Set for Treatment Period 1 (SAF-TP1) will include all patients who received at 
least one dose of study drug during this treatment period.
The Safety Set for Maintenance Treatment Period 2 (SAF-TP2) will include all patients 
who were randomized and received at least one dose of study drug at- or after the Week 24
visit. For safety evaluations, the patient groups of PASI 90 responders and PASI 75 
responders who do not achieve a PASI 90 response will be pooled; therefore, only 3 dosing 
groups will be compared: 

secukinumab 300 mg s.c. every 2 weeks (patients from Group 4)

secukinumab 300 mg s.c. every 4 weeks (patients from Group 1 pooled with Group 3)

secukinumab 300 mg s.c. every 6 weeks (patients from Group 2)
Patients will be analyzed according to the treatment they received.
The Full Analysis Set for Treatment Period 2 of PASI 90 Responders (FAS-P90R) will 
include all patients who are rated as PASI 90 responders at the Week 24 visit, were 
randomized to treatment groups 1 or 2 and who received at least one dose of study drug at- or 
after visit Week 24.
The Full Analysis Set for Treatment Period 2 of PASI 75 Responders who do not achieve 
a PASI 90 Response (FAS-P75P) will include all patients who are rated as PASI 75 
responders who do not achieve a PASI 90 response at visit Week 24, were randomized to 
treatment Group 3 or 4 and who received at least one dose of study drug at- or after visit 
Week 24.
The Per-Protocol Set for Treatment Period 2 of PASI 90 Responders (PP-P90R) will 
include all patients from the FAS-P90R who complete the study as scheduled without any 
major deviations from the protocol which may affect the primary outcome of this study. Such 
deviation will be defined in the Data Validation Plan or similar document and in the protocol 
of the blind data review without knowledge of the treatment group assignment.
Efficacy evaluations will be performed according to the treatment assigned at randomization.
9.2
Patient demographics and other baseline characteristics 
Summary statistics will be presented for continuous demographic and Baseline characteristics. 
The number and percentage of patients in each category will be presented for categorical 
variables. Separate tables will be produced for all patients treated (SAF-TP1, totals only) and 
 

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for patients randomized into the maintenance period (FAS-P90R and FAS-P75P, each by 
treatment group). 
9.2.1
Medical history
Any condition entered as medical history or current medical conditions at Baseline (including 
cardiovascular risk factors) will be coded using the MedDRA dictionary. They will be 
summarized by MedDRA system organ class (SOC) and preferred term of the MedDRA. 
Summaries for psoriasis specific medical history will also be provided.
9.3
Treatments 
The duration of exposure to study drug will be summarized for all patients treated (SAF-TP1, 
totals only) and for patients randomized into the maintenance period (FAS-P90R and FAS-
P75P, each by treatment group). 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 treatment 
Prior and concomitant medications will be summarized by treatment group 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. 
Medications will be presented in alphabetical order, by anatomical therapeutic classification 
(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 treatment in a particular anatomical main group.
In addition, significant prior and concomitant non-drug therapies and procedures will be 
summarized by primary SOC and MedDRA preferred term.
9.4
Analysis of the primary variable
9.4.1
Variable
The primary variable is the maintenance of the PASI 90 response rate at Week 52 in the 
FAS-P90R, which is the proportion of patients who maintain their PASI 90 response assessed 
at Week 24 also at Week 52. The aim of the primary analysis of this study will be to 
demonstrate the non-inferiority of the 6-weekly dosing group compared to the 4-weekly 
dosing group with respect to the primary endpoint in the FAS-P90R.
9.4.2
Statistical model, hypothesis, and method of analysis
The statistical null-hypothesis to be rejected is that the odds ratio of maintaining a PASI 90 
response for patients 4-weekly dosing versus patients on 6-weekly dosing exceeds the 
non-inferiority margin of 1+. 
 

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Let j denote the probability of a PASI 90 response at Week 52 for treatment group j, j=0, 1 
where 

0 corresponds to 4-weekly dosing

1 corresponds to 6-weekly dosing
The following hypothesis will be tested
H0.1: (0 /[1- 0])/ (1 /[1- 1]) ≥1+versus HA1: (0 /[1- 0])/ (1 /[1- 1]) < 1+
The primary analysis will be performed comparing dosing groups (Group 1 vs Group 2) with 
respect to the primary efficacy variable in a logistic regression model with the factors 
treatment, country, body weight (< 90 kg or ≥90 kg), and PASI 90 response (Y/N) at 
Week 16. The odds ratio with its corresponding 95% CI will be given (please notice that the 
upper limit of a 2-sided 95% CI is identical to the upper limit of a one-sided 97.5% CI, which
would correspond to a one-sided test with significance level 2.5%). Additionally, a (one-
sided) p-value for the shifted null-hypothesis will be computed.
9.4.3
Choice of the non-inferiority margin
Non-inferiority is defined as a difference in PASI 90 maintenance rate between 4- and 6-
weekly dosing not exceeding 15% on a rate difference scale. Data from a pooled CAIN457A
database (CAIN4572302 and CAIN4572303) suggest that the PASI 90 maintenance rate at 
Week 52 under 4-weekly dosing might be 81.8%. However, since the logistic regression 
model used for the primary analysis provides estimates on the odds-ratio scale, the numbers 
above have to be translated into this scale. Inserting these numbers into the respective 
formulas results in a non-inferiority-margin on the odds-ratio-scale of 1+= 2.23. 
Non-inferiority of 6-weekly vs 4-weekly dosing will be claimed, if the upper limit of the CI
for the odds ratio does not exceed 2.23. 
9.4.4
Handling of missing values/censoring/discontinuations
Patients who drop out prematurely and/or do not have a valid PASI assessment at Week 52 
will be counted as non-responders. Patients with major protocol violations, but with a valid 
PASI assessment will be included in the ITT-analysis with their observed response. 
The same algorithm will be used for the key secondary endpoint, the PASI 90 response in the 
FAS-P75P set. Missing values for other endpoints will not be replaced.
9.4.5
Supportive analyses 
The primary analysis will be repeated for the Per-Protocol Set (PP-P90R). The impact of 
missing values will be explored using multiple imputation as a sensitivity analysis. The raw 
(unadjusted) response rates and their difference will be computed with the corresponding CI
(option RISKDIFF in SAS PROC FREQ).
 

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9.5
Analysis of secondary variables
9.5.1
Efficacy variables
The key secondary variable is the PASI 90 response rate at Week 52 in the FAS-P75P, ie, the 
proportion of patients with a PASI 75 response but also less than a PASI 90 response at 
Week 24 who achieve a PASI 90 response at Week 52. The key secondary analysis of this 
study will be to demonstrate superiority of the shortened 2-weekly dosing group compared to 
the 4-weekly dosing group in the FAS-P75P.
The statistical null-hypothesis to be rejected are that the odds ratio of gaining a PASI 90 
response for patients on 2-weekly dosing versus patients on 4-weekly dosing = 1 
Let j denote the probability of a PASI 90 response at Week 52 for treatment group j, j = 0, 1 
where 

0 corresponds to 2-weekly dosing

1 corresponds to 4-weekly dosing
The following hypothesis will be tested
H0.2: (0 /[1- 0])/ (1 /[1- 1]) = 1 versus HA2: (0 /[1- 0])/ (1 /[1- 1]) ≠1
This analysis will be performed comparing dosing groups (Group 3 vs Group 4) with respect 
to the key secondary variable in a logistic regression model with the factors treatment, country 
and PASI response (75% to 82% or 83% to 89%) at Week 24. The odds ratio with its 
corresponding 95% CI and p-value will be presented.
The key secondary analysis will be included in a confirmatory testing strategy. The key
secondary hypothesis will be a priori ordered below the primary hypothesis. This means that 
no multiplicity adjustment of the significance level is required; however, confirmatory 
evidence will be claimed only if non-inferiority with regard to the primary endpoint has been 
successfully demonstrated before. Otherwise, the result for the secondary endpoint will be 
interpreted as being purely explorative, independent of the nominal p-value.
The time course of PASI response (absolute points and percentage change from Baseline) will 
be graphically displayed for treatment Group 1 to 4 as well as for the total Treatment Period 1 
set. All other secondary variables (IGA mod 2011, QoL) will be analyzed descriptively using 
means and SDs for continuous and absolute and relative frequencies for categorical variables. 
Appropriate statistical tests for group comparisons of these variables will be defined in the 
SAP.
9.5.2
Safety variables 
For safety-evaluations, the patient groups of PASI 90 responders and those who achieve 
PASI 75 but not PASI 90 will be pooled for Group 1 and Group 3; therefore, only 3 dosing 
groups will be compared: 

secukinumab 300 mg s.c. every 2 weeks (patients from Group 4).

secukinumab 300 mg s.c. every 4 weeks (patients from Group 1 pooled with Group 3).
 

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
secukinumab 300 mg s.c. every 6 weeks (patients from Group 2).
Patients will be analyzed according to the treatment they received.
Treatment emergent AEs (events started after the first dose of study drug or events present 
prior to the first dose of study drug but increased in severity based on preferred term) will be 
summarized. Only primary paths within MedDRA will be considered for AE reporting. 
AEs will be summarized by presenting, for each treatment group, the number and percentage 
of patients 

having any AE, 

having an AE in each primary SOC and 

having each individual AE (preferred term). 
Summaries will also be presented for AEs by severity and for study drug related AEs. If a 
patient reported more than one AE with the same preferred term, the AE with the greatest 
severity will be presented. If a patient reported more than one AE within the same primary 
SOC, the patient will be counted only once with the greatest severity at the SOC level, where 
applicable. 
These summaries will be presented separately for study periods (Treatment Period 1, 
Treatment Period 2, Post-Treatment Follow-up Period), and for complete treatment periods 
(Treatment Periods 1 and 2 and Follow-up). Separate summaries will be provided for deaths, 
SAEs, other significant AEs leading to discontinuation and AEs leading to study drug
discontinuation.
9.5.3
Resource utilization 
Data relating to resource utilization will be used for the purpose of economic evaluation 
which might be carried out and reported as a separate activity.
9.5.4
Pharmacokinetics
Exploratory analysis to investigate the correlation between the PK data and efficacy outcomes 
will be performed. An indirect response model, driven by study drug concentration, will be 
used to characterize the time course of PASI response. Further details of the modeling 
approach will be specified in a modeling plan.
9.5.5
Pharmacogenetics/pharmacogenomics
Not applicable.
9.5.6
Biomarkers
Not applicable.
9.6
Interim analyses 
No interim analysis is planned for this study.
 

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9.7
Sample size calculation
Based on the pooled data from the CAIN457A program (CAIN4572302 and CAIN4572303), 
the PASI 90 response rate for biologics-naïve patients treated with secukinumab 300 mg s.c.
was 74.3% at 24 weeks. Of those who were PASI 90 responders at Week 24, 81.8% of 
patients maintained their PASI 90 response until Week 52.
It is assumed that a dosing frequency of 6 weeks (Group 2) will differ in PASI 90 response up 
to 7% worse compared a dosing frequency of 4 weeks (Group 1). This assumption of a 
difference of maximally 7% is based on simulation of the PK levels obtained with 
maintenance treatments of secukinumab 300 mg every 6 weeks and the correlation between 
plasma levels and the clinical response seen in the secukinumab Phase 3 studies.
A total of 554 patients per group are required to achieve 90% power on a one-sided, 2.5% 
significance level to demonstrate the non-inferiority of 6-weekly vs 4-weekly dosing, if the 
true maintenance rates are 81.8% under 4-weekly and 74.8% under 6-weekly dosing and the 
non-inferiority margin is predefined as -15%.
The response rates underlying this estimation were obtained from pooled data of studies 
analyzed according to the ITT-principle using the same algorithm to handle drop-outs or 
protocol violations as in this present study. Therefore, the effect of drop-outs or protocol
violations should be already accounted for in the effect estimates and no further adjustments 
of the sample size are required. However, to account for the fact that there might be minor 
differences (eg with respect to drop-out rates) between the historical data and the data to be 
observed in this study, the sample size will be rounded up slightly to 570 patients/group who 
should be randomized to Group 1 or Group 2 (giving a total of 1140 patients in both groups) 
of this study.
Assuming a PASI 90 response rate of 74% at Week 24, 1580 patients should be enrolled at 
Baseline in this study in order to achieve the required sample size for randomization at 
Week 24. This number still allows for some drop-out patients or patients withdrawing consent 
at or after randomization even after experiencing a PASI 90 response.
9.7.1
Power for the key secondary objective
As per the sample size calculation for the primary objective, 1580 patients will be enrolled 
into Phase 1 of the study. In the secukinumab database (CAIN457A2302 and CAIN457A2303) 
13.3% of patients were in the category of PASI 75 but did not achieve PASI 90 at Week 24.
In the present study, this would translate into 210 patients fulfilling the criteria to be 
randomized into the partial responder part of the maintenance phase.
Prior Phase 3results (CAIN457A2302 and CAIN457A2303) suggest that the PASI responses 
reach a maximum at around 16 to 24 weeks with a sustained effect until Week 52. The PASI 
90 responder rate at Week 52 of patients treated with secukinumab 300 mg s.c. every 4 weeks
who have a PASI 75 but no PASI 90 response at Week 24 is estimated to be 3.8%. This rate 
may be increased by 14% (to then 18%) by increasing the dosing frequency to 2-weekly after 
Week 24.
A sample size of 210 patients (105 per group) will provide more than 90% power on a two-
sided, 95% significance level to detect differences in response rates for secukinumab 
 

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intensified 2-weekly dosing compared to every 4 weeks, if the responder rates in these groups 
are about 4% vs. 18% at Week 52. 
10
Ethical considerations 
10.1
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented and reported in accordance with 
the International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH) Harmonized Tripartite Guidelines for GCP, with 
applicable local regulations (including European Directive 2001/20/EC, US CFR 21, and 
Japanese Ministry of Health, Labor, and Welfare), 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 (ie, 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.
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 and IRB/IEC 
Before initiating a study, the Investigator/institution should obtain approval/favorable opinion 
from the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the study
protocol, written ICF, consent form updates, patient recruitment procedures (eg, 
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 
 

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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 investigational 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 CSR.
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. Only 
amendments that are required for patient safety may be implemented prior to IRB/IEC 
approval. 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, Novartis should be notified of this action and the IRB/IEC at the study center should be 
informed within 10 working days or less, if required by local regulations.
 

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References
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of subcutaneous TNF inhibitors in rheumatoid arthritis: design of a pragmatic randomised non 
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Gottlieb A, Griffiths CEM, Ho VC, et al (2005) Efficacy and tolerability of oral pimecrolimus 
in the treatment of moderate to severe chronic plaque type psoriasis: a double-blind, 
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Dermatol;65:870–873.
Kimball AB, Gordon KB, Fakharzadeh S, et al (2012) Long-term efficacy of ustekinumab in 
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psoriasis global assessment, and lattice system physician’s global assessment. J Am Acad 
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Papp KA, Matheson RT, Tu JH et al (2011) Secukinumab, a novel fully human antibody to 
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comparing efficacy of treatments for severe psoriasis. J Dermatolog Treat;14:158-165.
 

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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 except for the follow-up requirement for liver events as specified in 
Appendix 2, as it will be decided by the investigator/qualified study center 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. 
Liver Function and Related Variables (see also Appendix 2)
ALT (SGPT):
> 3 x Upper Limit of Normal (ULN)
AST (SGOT):
> 3 x ULN
Total bilirubin:
> 2 x ULN
Alkaline phosphatase:
> 2.5 x ULN
Renal Function and Electrolyte Variables
Creatinine (serum):
> 1.5 x ULN
Potassium:
> 6 mmol/L or < 3 mmol/L
Sodium:
> 160 mmol/L or <115 mmol/L
Hematology Variables
Hemoglobin:
≥ 20 g/L 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)
 

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Appendix 2: Liver event and laboratory trigger definitions 
and follow-up requirements
Table 14-1
Liver event definitions
Definition/ threshold
Liver event of special interest
Laboratory values
ALT (SGPT) or AST (SGOT) > 3 x ULN
ALP > 2 x ULN
TBL > 1.5 x ULN
Medically significant liver 
event (SAE)
Laboratory values
ALT or AST > 5 x ULN (with or without TBL > 2 x ULN [mainly 
conjugated fraction])
ALP > 5 x ULN (with or without TBL > 2 x ULN [mainly conjugated 
fraction])
TBL > 3 x ULN
Potential Hy’s Law cases (defined as ALT/AST > 3 x ULN and TBL 
> 2 x ULN [mainly conjugated fraction] without notable increase in 
ALP to > 2 x ULN)
Adverse events
Any clinical event of jaundice (or equivalent term)
ALT or AST > 3 x ULN accompanied by general malaise, fatigue, 
abdominal pain, nausea, or vomiting, or rash with eosinophilia
Any event that links to a preferred term (PT) in the MedDRA 
dictionary falling under the SMQ sub-module “Drug-related hepatic 
disorders – severe events only”* or any “Hy’s law case” PT
* These events cover the following: hepatic failure, fibrosis and cirrhosis, and other liver damage-
related conditions; the non-infectious hepatitis; the benign, malignant and unspecified liver neoplasms
ALT = alanine aminotransferase, ALP = alkaline phosphatase, AST = aspartate aminotransferase, 
SMQ = standard medical query, TBL = total bilirubin, UNL= upper normal limit
 

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Table 14-2
Liver event follow-up requirements
Criteria
Event type
Actions required
Follow-up monitoring
Potential Hy’s Law 
casea
Medically 
significant
Discontinue the study drug
immediately
Hospitalize, if clinically 
appropriate
Report to Novartis as an SAE
Establish causality
ALT, AST, TBL, Alb, PT, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion)
ALT or AST
> 8 x ULN
Medically 
significant
Repeat LFT within 48 hours
If elevation persists, discontinue 
the study drug immediately
Hospitalize if clinically 
appropriate
Report to Novartis as an SAE
Establish causality
ALT, AST, TBL, Alb, PT, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion)
> 5 to ≤ 8 x ULN
Medically 
significant
Repeat LFT within 48 hours
If elevation persists for more 
than 2 weeks, discontinue the 
study drug
Report to Novartis as an SAE
Establish causality
ALT, AST, TBL, Alb, PT, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion)
> 3 x ULN
accompanied by 
symptomsb
Medically 
significant
Discontinue the study drug
immediately
Hospitalize if clinically 
appropriate
Report to Novartis as an SAE
Establish causality
ALT, AST, TBL, Alb, PT, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion)
> 3 to ≤ 5 x ULN 
(patient is 
asymptomatic)
AESI
Central laboratory to report to 
Investigator and Novartis
Repeat LFT once or twice in the 
week
If elevation persists, establish 
causality
Investigator discretion
Monitor LFT within 1 to 4 
weeks or at next visit
≤ 3 x ULN 
(patient is 
asymptomatic)
N/A
Repeat LFT at next visit
ALP (isolated)
> 5 x ULN
Medically 
significant
Repeat LFT within 48 hours
If elevation persists, report to 
Novartis as an SAE
Establish causality
Investigator discretion
Monitor LFT within 1 to 4 
weeks or at next visit
> 2 to ≤5 x ULN 
(patient is 
asymptomatic)
AESI
Central laboratory to report to 
Investigator and Novartis
Repeat LFT once or twice in the 
week If elevation persists, 
Investigator discretion
Monitor LFT within 1 to 4 
weeks or at next visit
 

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Criteria
Event type
Actions required
Follow-up monitoring
establish causality
≤ 2 x ULN
(patient is 
asymptomatic)
N/A
Repeat LFT at next visit
TBL (isolated)
> 3 x ULN
Medically 
significant
Repeat LFT within 48 hours
If elevation persists, discontinue 
the study drug immediately
Hospitalize if clinically 
appropriate
Report to Novartis as an SAE
Establish causality
ALT, AST, TBL, Alb, PT, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion)
Test for hemolysis (eg, 
reticulocytes, haptoglobin, 
unconjugated [indirect] 
bilirubin)
> 1.5 to ≤ 3 x ULN
(patient is 
asymptomatic)
AESI
Central laboratory to report to 
Novartis
Repeat LFT once or twice in the 
week. If elevation persists, 
establish causality
investigator discretion
Monitor LFT within 1 to 4 
weeks or at next visit
≤ 1.5 x ULN
(patient is 
asymptomatic)
N/A
Repeat LFT at next visit
Preferred terms
Jaundice
Medically 
significant
Discontinue the study drug
immediately
Hospitalize the patient
Report to Novartis as an SAE
Establish causality
ALT, AST, TBL, Alb, PT, 
ALP and GGT until 
resolutionc (frequency at 
investigator discretion)
“Drug-related 
hepatic 
disorders - severe 
events only” SMQ 
AE
Medically 
significant
Discontinue the study drug
hospitalization if clinically 
appropriate
Report to Novartis as an SAE
Establish causality
Investigator discretion
a
Elevated ALT/AST > 3 x ULN and TBL > 2 x ULN but with no notable increase in ALP to > 2 x ULN
b
General malaise, fatigue, abdominal pain, nausea, or vomiting, rash with eosinophilia
c
Resolution is defined as an outcome of one of the following: return to Baseline values, stable 
values at 3 subsequent monitoring visits at least 2 weeks apart, remain at elevated level after a 
maximum of 6 months, liver transplantation, and death.
Alb = albumin, AESI = adverse event of special interest, ALP = alkaline phosphatase, GGT = gamma 
glutamyl transferase, LFT = liver function test, PT = prothrombin time, SMQ = standard medical 
query, TBL = total bilirubin, UNL= upper normal limit