Clinical trial NCT01640951
Conditions: Moderate to Severe Chronic Plaque-Type Psoriasis
Keywords: Psoriasis Plaque Inflammatory skin disease Scaly patches AIN457 Secukinumab Moderate to Severe Plaque-type Psoriasis
Sponsor: Novartis Pharmaceuticals
Start date: 2012-09-16; Completion date: 2017-05-04
Enrollment: 675 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
CAIN457A2304E1 was an extension study to two phase III studies, CAIN457A2304 and CAIN457A2307 (core studies). This extension study planned to collect up to four years of long-term safety, tolerability and efficacy data of secukinumab in both the fixed interval regimen and the retreatment at start of relapse regimen. All subjects who completed the full study treatment period (52 weeks) in the cores studies CAIN457A2304 and CAIN457A2307 were eligible to participate in this extension study. In this extension study, the prefilled syringe (PFS) liquid formulation of secukinumab was used.

Detailed description:

Arms: arm 1: 1 s.c. Secukinumab 150 mg Pre-filled seringue (PFS) injection + 1 s.c. Placebo (PBO) Secukinumab PFS injection every 4 weeks arm 2: Start of relapse: 1 s.c. Secukinumab 150 mg PFS injection + 1 s.c. PBO Secukinumab PFS injection every 4 weeks

Otherwise: 2 s.c. PBO Secukinumab PFS injections every 4 weeks arm 3: 2 s.c. Secukinumab 150 mg PFS injections every 4 weeks arm 4: Start of relapse: 2 s.c. Secukinumab 150 mg PFS injection every 4 weeks

Otherwise: 2 s.c. PBO Secukinumab PFS injections every 4 weeks arm 5: Open Label - Secukinumab 300mg every 4 weeks
Interventions: intervention 1: AIN457 150 mg intervention 2: AIN457 300 mg intervention 3: Placebo
Intervention descriptions: intervention 1: (1 injection per dose) and placebo to Secukinumab 150 mg intervention 2: Secukinumab 150 mg (2 injections per dose) intervention 3: None

Protocol documents:
Prot_000.pdf: 
Clinical Development 
AIN457/ secukinumab 
Clinical Trial Protocol CAIN457A2304E1 / NCT01640951 
A multicenter, double-blind and open label, 4 year 
extension study of subcutaneous secukinumab in prefilled 
syringes, assessing long-term safety, tolerability and 
efficacy in subjects with moderate to severe chronic 
plaque-type psoriasis treated with either a fixed dose 
regimen or on a retreatment at start of relapse regimen 
Authors: 
 
Document type: 
Amended Protocol Version  
EUDRACT number: 
2012-000985-39 
Version number: 
v02 Clean 
Development phase: 
III 
Release date: 
29-Apr-2015
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
NCDS Template Version 03-Feb-2012 


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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 5 
List of figures ...................................................................................................................... 5 
List of abbreviations ............................................................................................................ 6 
Glossary of terms ................................................................................................................. 8 
Amendment 2 ........................................................................................................................... 10 
Amendment 1, 25-Apr-2014..................................................................................................... 12 
Protocol synopsis ............................................................................................................... 14 
1 
Introduction ....................................................................................................................... 18 
1.1 
Background ............................................................................................................ 18 
1.2 
Purpose .................................................................................................................. 18 
2 
Study objectives ................................................................................................................. 19 
2.1 
Primary and key secondary objectives .................................................................. 19 
2.2 
Secondary objectives ............................................................................................. 19 
2.3 
Exploratory objectives ........................................................................................... 20 
3 
Investigational plan ........................................................................................................... 20 
3.1 
Study design........................................................................................................... 20 
3.2 
Rationale of study design ....................................................................................... 23 
3.3 
Rationale of dose/regimen, route of administration and duration of treatment ..... 24 
3.4 
Rationale for choice of comparator ....................................................................... 24 
3.5 
Purpose and timing of interim analyses/design adaptations .................................. 24 
3.6 
Risks and benefits .................................................................................................. 25 
4 
Population .......................................................................................................................... 25 
4.1 
Inclusion criteria .................................................................................................... 26 
4.2 
Exclusion criteria ................................................................................................... 26 
5 
Treatment ........................................................................................................................... 27 
5.1 
Protocol requested treatment ................................................................................. 28 
5.1.1 
Investigational treatment ....................................................................... 28 
5.1.2 
Additional study treatment .................................................................... 28 
5.2 
Treatment arms ...................................................................................................... 28 
5.3 
Treatment assignment ............................................................................................ 31 
5.4 
Treatment blinding ................................................................................................. 31 
5.5 
Treating the patient ................................................................................................ 32 
5.5.1 
Patient numbering ................................................................................. 32 
5.5.2 
Dispensing the investigational treatment .............................................. 32 


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5.5.3 
Handling of study treatment .................................................................. 32 
5.5.4 
Instructions for prescribing and taking study treatment ........................ 33 
5.5.5 
Permitted dose adjustments and interruptions of study treatment ........ 35 
5.5.6 
Rescue medication ................................................................................ 35 
5.5.7 
Concomitant treatment .......................................................................... 35 
5.5.8 
Prohibited Treatment ............................................................................. 36 
5.5.9 
Discontinuation of study treatment and premature patient 
withdrawal ............................................................................................. 37 
5.5.10 
Emergency breaking of treatment assignment ...................................... 38 
5.5.11 
Study completion and post-study treatment .......................................... 39 
5.5.12 
Early study termination ......................................................................... 39 
6 
Visit schedule and assessments ......................................................................................... 39 
6.1 
Information to be collected on screening failures .................................................. 47 
6.2 
Patient demographics/other baseline characteristics ............................................. 47 
6.3 
Treatment exposure and compliance ..................................................................... 47 
6.4 
Efficacy .................................................................................................................. 47 
6.4.1 
Investigator’s global assessment (IGA mod 2011) ............................... 48 
6.4.2 
Assessment of the psoriasis area and severity index (PASI) ................ 48 
6.4.3 
Appropriateness of efficacy assessments .............................................. 51 
6.5 
Safety ..................................................................................................................... 51 
6.5.1 
Physical examination ............................................................................ 51 
6.5.2 
Vital signs.............................................................................................. 52 
6.5.3 
Height and weight ................................................................................. 52 
6.5.4 
Laboratory evaluations .......................................................................... 52 
6.5.5 
Electrocardiogram (ECG) ..................................................................... 54 
6.5.6 
Pregnancy and assessments of fertility ................................................. 54 
6.5.7 
Appropriateness of safety measurements .............................................. 54 
6.6 
Other assessments .................................................................................................. 54 
6.6.1 
Fasting laboratory evaluations .............................................................. 55 
6.6.2 
Resource utilization ............................................................................... 55 
6.6.3 
Health-related Quality of Life ............................................................... 55 
6.6.4 
Pharmacokinetics .................................................................................. 57 
 
 58 
6.6.6 
Other biomarkers ................................................................................... 58 
7 
Safety monitoring .............................................................................................................. 59 
7.1 
Adverse events ....................................................................................................... 59 


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7.2 
Serious adverse event reporting ............................................................................. 61 
7.3 
Liver safety monitoring ......................................................................................... 62 
7.4 
Pregnancy reporting ............................................................................................... 62 
7.5 
Prospective suicidality assessment ........................................................................ 63 
8 
Data review and database management ............................................................................. 63 
8.1 
Site monitoring ...................................................................................................... 63 
8.2 
Data collection ....................................................................................................... 63 
8.3 
Database management and quality control ............................................................ 64 
8.4 
Data Monitoring Committee .................................................................................. 64 
8.5 
Adjudication Committee ........................................................................................ 64 
9 
Data analysis ...................................................................................................................... 64 
9.1 
Analysis sets .......................................................................................................... 65 
9.2 
Patient demographics and other baseline characteristics ....................................... 65 
9.3 
Treatments ............................................................................................................. 66 
9.4 
Analysis of the primary and key secondary variable(s) ......................................... 66 
9.4.1 
Variable(s) ............................................................................................. 66 
9.4.2 
Statistical model, hypothesis, and method of analysis .......................... 66 
9.4.3 
Handling of missing values/censoring/discontinuations ....................... 67 
9.4.4 
Supportive analyses ............................................................................... 67 
9.5 
Analysis of secondary variables ............................................................................ 67 
9.5.1 
Efficacy variables .................................................................................. 67 
9.5.2 
Safety variables ..................................................................................... 68 
9.5.3 
Resource utilization ............................................................................... 69 
9.5.4 
Health-related Quality of Life ............................................................... 69 
9.5.5 
Pharmacokinetics .................................................................................. 70 
 
 70 
9.5.7 
Biomarkers ............................................................................................ 71 
9.5.8 
PK/PD ................................................................................................... 71 
9.6 
Interim analyses ..................................................................................................... 71 
9.7 
Sample size calculation .......................................................................................... 71 
10 Ethical considerations ........................................................................................................ 71 
10.1 
Regulatory and ethical compliance ........................................................................ 71 
10.2 
Informed consent procedures ................................................................................. 72 
10.3 
Responsibilities of the investigator and IRB/IEC .................................................. 72 
10.4 
Publication of study protocol and results............................................................... 72 
11 Protocol adherence ............................................................................................................ 72 


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11.1 
Protocol Amendments ........................................................................................... 73 
12 References ......................................................................................................................... 73 
13 Appendix 1: Clinically notable laboratory values and vital signs ..................................... 75 
14 Appendix 2: Liver event definitions and follow-up requirements .................................... 76 
15 Appendix 3: Blood collection log for pharmacokinetics (PK) and immunogenicity 
(IG) .................................................................................................................................... 79 
16 Appendix 4: Pharmacokinetics (PK) and immunogenicity (IG) sample labeling 
information ........................................................................................................................ 81 
16.1.1 
PK sample handling .............................................................................. 81 
16.1.2 
IG sample handling ............................................................................... 81 
 
List of tables 
Table 5-1 
Open-label treatment options starting at Week 156 .............................. 29 
Table 5-2 
Overview of treatment between Week 52 and Week 152 ..................... 30 
Table 5-3 
Overview of treatment between Week 156 and Week 256 ................... 30 
Table 5-4 
Prohibited treatment .............................................................................. 36 
Table 6-1 
Assessment schedule ............................................................................. 41 
Table 6-2  
The IGA mod 2011 rating scale ............................................................ 48 
Table 6-3 
The PASI scoring system ...................................................................... 49 
Table 14-1 
Liver Event Definitions ......................................................................... 76 
Table 14-2 
Liver Event Follow Up Requirements .................................................. 77 
Table 15-1 
Blood collection log for PK .................................................................. 79 
Table 15-2 
Blood collection log for IG ................................................................... 80 
 
List of figures 
Figure 3-1 
Study design .......................................................................................... 23 
 


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List of abbreviations 
AE 
 
 
adverse event 
ALT 
 
 
alanine aminotransferase 
AST 
 
 
aspartate aminotransferase 
CHMP            
 
the European Union Committee for Medicinal Products for Human Use 
CRF 
 
 
Case Report/Record Form (paper or electronic) 
CPO  
 
Country Pharma Organization 
CRO  
 
Contract Research Organization 
CS 
 
 
Corticosteroid (s) 
DLQI  
 
Dermatology Life Quality Index© 
DMC  
 
Data Monitoring Committee 
DS&E  
 
Drug Safety & Epidemiology 
ECG  
 
Electrocardiogram 
EDC  
 
Electronic Data Capture 
EQ-5D  
 
Euro-QoL 5-Dimension Health© Questionnaire  
ICH 
International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use 
HAQ  
 
Health Assessment Questionnaire 
HAQ-DI 
 
Health Assessment Questionnaire-Disability Index 
IEC 
 
 
Independent Ethics Committee 
IGA 
 
 
Investigator’s Global Assessment 
IGA mod 2011  
Novartis Invetigator’s global assessment modified 2011 
IG 
 
 
Immunogenicity 
IIS 
 
 
Integrated Information Sciences 
IRB 
 
 
Institutional Review Board 
IRT 
 
 
Interactive Response Technology 
i.v. 
 
 
intravenous 
MedDRA 
 
Medical Dictionary for Regulatory Activities 
OC/RDC 
 
Oracle Clinical/Remote Data Capturing 
PASI  
 
Psoriasis Area and Severity Index 
PD 
 
 
Pharmacodynamic (s) 
PFS 
 
 
Pre-filled syringe 


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PK 
 
 
Pharmacokinetic (s) 
PsA 
 
 
Psoriatic Arthritis 
PUVA  
 
Psoralen+UVA treatment  
SAE 
 
 
serious adverse event 
s.c. 
 
 
Subcutaneous 
SoR 
 
 
Start of Relapse 
VAS  
 
visual analog scale 


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Glossary of terms 
 
Assessment 
A procedure used to generate data required by the study 
Control drug 
Drugs(s) used as a comparator to reduce assessment bias, 
preserve blinding of investigational drug, assess internal study 
validity, and/or evaluate comparative effects of the investigational 
drug 
Enrollment 
Point/time of patient entry into the study; the point at which 
informed consent must be obtained (i.e. prior to starting any of 
the procedures described in the protocol) 
Epoch  
The planned stage of the subjects’ participation in the study. 
Each epoch serves a purpose in the study as a whole. Typical 
epochs are: determination of subject eligibility, wash-out of 
previous treatments, exposure of subject to treatment or to 
follow-up on subjects after treatment has ended. 
Investigational drug 
The drug whose properties are being tested in the study; this 
definition is consistent with US CFR 21 Section 312.3 and is 
synonymous with “investigational new drug” or “investigational 
medicinal product.” 
Investigational treatment 
All investigational drug(s) whose properties are being tested in 
the study as well as their associated treatment controls.  
This includes any placebos, any active controls, as well as 
approved drugs used outside of their indication/approved dosage 
or tested in a fixed combination.  
Investigational treatment generally does not include other 
treatments administered as concomitant background therapy 
required or allowed by the protocol when used within approved 
indication/dosage 
Medication number 
A unique identifier on the label of each investigational/study drug 
package in studies that dispense medication using an IRT 
system 
Subject Number  
A number assigned to each patient who enrolls into the study  
Part  
A subdivision of a single protocol into major design components. 
These parts often are independent of each other and have 
different populations or objectives. For example, a single dose 
design, a multiple dose design that are combined into one 
protocol, or the same design with different patient populations in 
each part. 
Period 
A subdivision of a cross-over study 
Premature patient withdrawal 
Point/time when the patient exits from the study prior to the 
planned completion of all investigational/study treatment 
administration and all assessments (including follow-up) 
Randomization number 
A unique identifier assigned to each randomized patient, 
corresponding to a specific treatment arm assignment 
Rebound 
A subject experiences a rebound, if PASI increases to > 125% of 
baseline PASI, or if new pustular psoriasis, or new erythrodermic 
psoriasis, or more inflammatory psoriasis occurs within 8 weeks 
after the last dose of study treatment has been received. 


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Stop study participation 
Point/time at which the patient came in for a final evaluation visit 
or when study/investigational treatment was discontinued 
whichever is later 
Study drug/ treatment 
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  
Study/investigational treatment 
discontinuation 
Point/time when patient permanently stops taking 
study/investigational treatment  for any reason; may or may not 
also be the point/time of premature patient withdrawal 
Variable 
Information used in the data analysis; derived directly or 
indirectly from data collected using specified assessments at 
specified time points 


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Amendment 2 
Amendment rationale  
FDA has requested the following post marketing commitment be applied to this study: 
"Complete the treatment and evaluation of subjects enrolled in the ongoing CAIN457A2304E1 
trial for a duration of 4 years, unless a safety signal is identified that indicates the potential 
risks of such continued long-term treatment outweigh the benefits. Evaluation of subjects should 
continue through the end of the trial when achievable (even if treatment is not continued for the 
duration). Subjects will be followed for the occurrence of serious infection, tuberculosis, 
opportunistic infections, malignancy, hypersensitivity reactions, autoimmune disease, 
neurologic or demyelinating disease, cardiovascular, gastrointestinal or hematologic adverse 
events". 
Subjects who complete treatment period and follow-up period are evaluated for 4 years 
regarding respective adverse events.  However, patient who prematurely discontinue treatment 
are evaluated for less than 4 years. 
Therefore, this amendment extends the evaluation of subjects who prematurely discontinue 
treatment regarding respective adverse events and concomitant medications in order to achieve 
a 4 year evaluation period. Evaluation of subjects should continue when achievable even if 
treatment is not continued for the duration. All subjects who prematurely discontinue treatment 
should complete all assessment of Week 260 (end of treatment visit) and of the follow-up period 
visits (Weeks 264 and 268). Subsequently, adverse events and use of concomitant medication 
will be evaluated by the investigator through telephone calls every 3 months for a duration of 4 
years from the time when subject has been enrolled into CAIN457A2304E1 study. If deemed 
necessary by the investigator unplanned assessments at site might be scheduled during this time.  
In addition, the study will NOT be terminated in selected countries where the drug is 
commercially available. 
Changes to the protocol 
The protocol introduces a follow-up 2 period to assess adverse events and concomitant 
medications through telephone calls for all subjects who have prematurely discontinued 
treatment. 
Section 3.1, Figure 3-1, Section 6 and Table 6-1 were updated to introduce follow-up 2 period 
Section 3.1 and Section Section 5.5.11 were updated to reflect that the study will NOT be 
terminated in selected countries where the drug is commercially available. 
Section 3.5 was updated to specify the impact of follow-up 2 period on final database lock 
Section 5.5.9 was updated to specify that subjects who prematurely discontinue treatment 
should enter follow-up 2 period  after completion of follow-up period assessments 
Section 5.5.10 was updated to reflect that subjects who are prematurely unblinded and  
discontinued from treatment should also enter follow-up 2 period.   


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Section 7.2 was updated to reflect that SAE reporting is extended for subjects who enter follow-
up 2 period 
Table 6-1 was updated to align dosing schedule with the text of the protocol section  
Section 9.2 was updated to reflect that the test of baseline balance is not considered as 
appropriate use of significance test and may cause misinterpretation of the data 
Section 9.5.2 was updated to specify the data collection within the follow-up 2 period 
Other minor corrections, clarifications, and editing changes of the protocol text were made in 
various sections 
All 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.  The changes herein affect the Informed Consent, and sites are required to 
update and submit for approval a revised Informed Consent that takes into account the changes 
described in this amended protocol. 


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Amendment 1, 25-Apr-2014 
Amendment rationale  
The results of protocol CAIN457A2304 showed that the re-treatment at start of relapse 
maintenance regimen (SoR) was not non-inferior to a fixed interval regimen (FI) with treatment 
every four weeks and that patients experienced better maintenance of effect with secukinumab 
300 mg compared to secukinumab 150 mg; therefore, this amendment introduces an opportunity 
at week 156 for blinded subjects to 1) switch off of the SoR treatment regimen to treatment 
every four weeks and 2) to increase the secukinumab dose to 300 mg.  All subjects will be 
unblinded at Week 156 and the investigator may switch to the subject one of these open label 
treatment option(s) depending on the current treatment assignment: 
 
Previous treatment arm through 
Week 152 (Unblinded at Week 
156) 
Treatment options, as decided by the 
investigator 
Office visit frequency 
after Week 156 
Secukinumab 300 mg FI 
Continue secukinumab 300 mg FI 
Every 12-16 weeks 
Secukinumab 300 mg SoR 
Continue secukinumab 300 mg SoR 
for remainder of the study  
Every 4 weeks 
 
OR Switch to secukinumab 300 mg 
dosed every 4 weeks 
Every 12-16 weeks 
Secukinumab 150 mg FI 
Continue secukinumab 150 mg FI 
Every 12-16 weeks 
 
OR Switch to secukinumab 300 mg 
dosed every 4 weeks  
Every 12-16 weeks 
Secukinumab 150 mg SoR 
Continue secukinumab 150 mg SoR 
for remainder of the study 
Every 4 weeks 
 
OR Switch to secukinumab 300 mg 
dosed every 4 weeks  
Every 12-16 weeks 
Additionally, this amendment extends the treatment duration for an additional 104 weeks (for 
a total of 5 years, one year in the core study or studies and four years in the extension study) 
and the opportunity for home administration of the study drug. In case secukinumab becomes 
commercially available in a participating country, the study might be discontinued in the 
respective country. This extension of treatment will allow for safety, tolerability, and efficacy 
data to be collected from the participating subjects for up to a total of 5 years.  
At the time of this amendment, recruitment is complete with 675 subjects randomized into the 
trial across 15 countries and 112 sites and approximately 108 subjects have discontinued from 
the study.  Since recruitment is complete and there is no change to protocol-mandated 
discontinuation, it is not expected that this amendment will have an impact on the study 
population or have a significant impact on the primary objective of the trial. 
Changes to the protocol 
The main changes throughout the protocol introduce an opportunity for subjects to switch to 
treatment with open label secukinumab 300 mg s.c.  and to extend the treatment duration for an 
additional 104 weeks (two years) with the option for home administration in patients receiving 
secukinumab every four weeks. 


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These specific changes were made to the protocol: 
• The length of the trial was changed from 2 to 4 years and visit names were updated as 
appropriate throughout the document: 
• Final treatment visit changed from Week 152 to Week 256 
• End of  Treatment period changed from Week 156 to Week 260 
• First Treatment-Free Follow-Up visit was changed from Week 160 to Week 264 
• End of Study changed from Week 164 to Week 268. 
• The synopsis was updated to reflect the changes in the main protocol text. 
• Section 3.1 was updated to introduce unblinding of blinded patients at Week 156, the 
subsequent option to switch to open label treatment with secukinumab 300 mg s.c. every 
four weeks, and to allow the subjects to self-inject at home.   
• Figure 3-1 was updated to reflect the new study design. 
• Section 3.2 was updated to reflect when combined with the core studies the trial will 
provide data on patients treated with secukinumab for five years.  
• Section 3.3 was updated with the primary conclusion of trial CAIN457A2304. 
• The risks and benefits of secukinumab were updated in Section 3.6 according to the 
increased experience and data reported in the Investigators Brochure Edition 13.   
• Section 3.6 refers to the Investigator Brochure for the most updated risk/benefit profile. 
• The section on treatment (Section 5) was updated throughout to reflect the unblinding of 
patients at Week 156 and the subsequent option to switch to treatment with open-label 
secukinumab 300 mg s.c. every four weeks, and to allow the subject to self-inject at home.  
Details of the treatment options are included in Section 5.2 and Table 5-1. Table 5-3 was 
added to summarize the overview of treatment and frequency of office visits between 
Week 156 and Week 256.  Details on instructions for home administrations are introduced 
in Section 5.5.4. 
• Section 5.5.8  and Table 5-4 were updated to further clarify the use of prohibited 
concomitant treatment given the increased experience with the study drug. 
• Section 5.5.10, Section 6.5.4.4, and Section 6.6.4 were updated to remove reference to the 
defunct position Clinical Trial Head  
• Section 5.5.11 was updated to specify that in case secukinumab becomes commercially 
available in a participating country prior to all patients completing the study in that 
country, the study might be discontinued in the respective country.  
• Section 6 and Table 6-1 were updated with assessments for Week 160 through Week 268 
• Section 9 was updated to include the secukinumab 300 mg open-label switch group for 
analysis 
• Section 9.4.3 was updated to define how data for the patients who switch to secukinumab 
300 mg open-label will be analyzed with respect to endpoints. 
• Appendix 3 was updated with the increased duration of the study. 
Other minor corrections, clarifications, and editing changes of the protocol text were made in 
various sections 


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Protocol synopsis 
 
Protocol number 
CAIN457A2304E1 
Title 
A multicenter, double-blind and open label, 4 year extension study of 
subcutaneous secukinumab in prefilled syringes, assessing long-term 
safety, tolerability and efficacy in subjects with moderate to severe chronic 
plaque-type psoriasis treated with either a fixed dose regimen or on a 
retreatment at start of relapse regimen 
Brief title 
 
4 year Extension Study of efficacy and safety of secukinumab in Patients 
with moderate to severe chronic plaque-type psoriasis  
Sponsor and Clinical 
Phase 
Novartis  
Phase 3 
Investigation type 
Drug 
Study type 
Interventional 
Purpose and rationale 
To assess long-term safety and maintenance of efficacy in two different 
treatment regimens, a “fixed dose” regimen and a “retreatment at start of 
relapse” regimen. 
This four year (208 weeks), multicenter, double-blind and open label, 
extension study will collect long-term efficacy, safety and tolerability of 
secukinumab in the fixed dose and start of relapse treatment regimens.   
Primary Objective(s) 
and Key Secondary 
Objective 
Objective: To assess long-term safety and tolerability of secukinumab in 
subjects with moderate to severe chronic plaque-type psoriasis who 
completed 
treatment 
in 
the 
core 
studies 
CAIN457A2304 
and 
CAIN457A2307.  
Secondary Objectives 
 
• 
To evaluate the long-term efficacy of secukinumab administered 
at the start of relapse versus fixed interval regimens, in subjects 
with moderate to severe chronic plaque-type psoriasis who are 
PASI 75 responders at Week 12, with respect to PASI 75 
response: 
• 
at Weeks 104 and 156, for subjects in the fixed interval 
regimens, or 
• 
at Weeks 92 and 144, for subjects in the retreatment at start 
of relapse regimen who do not require active treatment at 
Week 92 or 144, respectively, or 
• 
at Weeks 104 and 156, for subjects in the retreatment at 
start of relapse regimen who do require active treatment at 
Week 92 or 144, respectively. 
• 
To evaluate the efficacy of secukinumab treatment regimens in 
subjects with moderate to severe chronic plaque-type psoriasis 
with respect to PASI 50/75/90/100 and IGA 0 or 1 response over 
time.   
• 
To evaluate the effects of treatment regimens with secukinumab 
in subjects with moderate to severe chronic plaque type psoriasis 
with respect to PASI score and IGA mod2011 score over time  
• 
To assess the effects of secukinumab treatment regimens with 
respect to EQ-5D score over time 


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• 
To investigate the effects of treatment regimens with 
secukinumab in subjects with moderate to severe chronic plaque-
type psoriasis with respect to changes in DLQI over time 
• 
To investigate the effects of treatment regimens with 
secukinumab in subjects with moderate to severe chronic plaque-
type psoriasis with respect to DLQI 0 or 1 achievement over time 
• 
To investigate the potential development of immunogenicity 
against secukinumab 
Study design 
This is a multicenter, double-blind and open label, trial in subjects with 
moderate to severe chronic plaque-type psoriasis who completed treatment 
in the maintenance period of studies CAIN457A2304 or CAIN457A2307. 
This extension study consists of three to four periods: the screening period, 
the treatment period, the treatment- free follow-up period (for all subjects), 
and the follow-up 2 period (only for subject who prematurely discontinued 
treatment). 
Population 
All subjects who complete treatment in the maintenance period of studies 
CAIN457A2304 or CAIN457A2307 and meeting inclusion & exclusion 
criteria are eligible for this study. Approximately 740 subjects are expected 
to be recruited in this study. When recruitment was complete, 675 subjects 
had been enrolled at 112 sites.    
Inclusion criteria 
Subjects eligible for inclusion in this study have to fulfill all of the following 
criteria: 
• 
Subjects 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 according to 
local laws and regulations. 
• 
Subjects who complete Week 52 of study CAIN457A2304 or 
complete Week 40 of study CAIN457A2307  
• 
Subjects expected to benefit from participation in the extension 
study, as assessed by the subject and investigator 
Exclusion criteria 
Subjects fulfilling any of the following criteria are NOT eligible for inclusion 
in this study: 
• 
A protocol deviation in the core studies which according to the 
investigator will prevent the meaningful analysis of the extension 
study for the individual subject 
• 
Ongoing use of prohibited psoriasis or non-psoriasis treatments. 
Time period from last use of prohibited treatments in the core 
study to first dose of study drug in this extension study detailed in 
Table 5-4 must be adhered to. 
• 
Subjects expected to be exposed to an undue safety risk if 
participating in the trial 
• 
Current severe progressive or uncontrolled disease which in the 
judgment of the investigator renders the subject unsuitable for the 
trial 
• 
Plans for administration of live vaccines during the study period 
• 
Pregnant or nursing (lactating) women, where pregnancy is 
defined as the state of a female after conception and until the 


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termination of gestation, confirmed by a positive hCG laboratory 
test (>10 mIU/mL). 
• 
Women of child-bearing potential, defined as all women 
physiologically capable of becoming pregnant, unwilling to use 
effective contraception during the study and for a minimum of 16 
weeks after stopping treatment. 
Investigational and 
reference therapy 
Secukinumab Prefilled Syringes for s.c. administration 
Placebo Secukinumab Prefilled Syringes for s.c. administration 
Efficacy assessments 
Investigator’s Global Assessment (IGA mod 2011; scale from 0 – 4) 
Psoriasis Area and Severity Index (PASI; score from 0 – 72) 
Rebound assessment 
Safety assessments 
Evaluation of all AEs and SAEs including injection site reactions  
Physical examination 
Vital signs 
Laboratory evaluations 
Hematology 
Clinical chemistry 
Urinalysis 
Immunogenicity (assessment of anti-secukinumab antibody development) 
Electrocardiogram  
Pregnancy and assessments of fertility 
Other assessments 
Fasting laboratory evaluations,  
Health-related quality of life assessments such as 
DLQI 
EQ-5D 
HAQ-DI (only in subjects with psoriatic arthritis from study CAIN457A2304, 
not CAIN457A2307) 
PK assessments 
Data analysis 
Treatment groups for analysis will include: 
Secukinumab 150 mg fixed interval 
Secukinumab 300 mg fixed interval 
Secukinumab 150 mg start of relapse 
Secukinumab 300 mg start of relapse 
Secukinumab 300 mg open-label 
Secukinumab 300 mg open-label switch 
The primary analysis will focus on safety variables. All safety evaluations 
will be performed on the Safety set (all subjects who took at least one dose 
of study treatment during the treatment period.)  


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Maintenance of response will be defined analogously as in the primary 
endpoint in CAIN457A2304, but for week 104 and 156, i.e. PASI 75 
response 
at Weeks 104 and 156, for subjects in the fixed interval regimens, or 
at Weeks 92 and 144, for subjects in the retreatment at start of relapse 
regimen who do not require active treatment at Week 92 or 144, 
respectively, or 
at Weeks 104 and 156, for subjects in the retreatment at start of relapse 
regimen who do require active treatment at Week 92 or 144, respectively. 
Key words 
4 year Extension Study, in Patients with moderate to severe chronic plaque 
type psoriasis  
 


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1 
Introduction 
1.1 
Background  
CAIN457A2304E1 is an extension study to two phase III studies, CAIN457A2304 and 
CAIN457A2307 (core studies).  Study CAIN457A2304 compares the maintenance of efficacy 
and safety over time in two different treatment regimens: a fixed dose regimen and a retreatment 
at start of relapse regimen.  Efficacy is measured with PASI response rates; a PASI 75 is defined 
as a responder whereas a PASI 50 to less than PASI 75 is a partial responder.  In study 
CAIN457A2304, PASI 75 responders at Week 12 continued to the end of the study but partial 
responders were offered either participation in study CAIN457A2307 or entering the treatment-
free follow-up period in CAIN457A2304. Study CAIN457A2304 non-responders at week 12 
(PASI response less than 50) were discontinued from treatment and entered the treatment-free 
follow-up period in CAIN457A2304. 
Study CAIN457A2307 evaluates whether a partial responder can be converted to a responder 
when treated for longer periods of time and/or when treated with a higher dose of the drug via 
either the s.c. or the i.v. route of administration. Please refer to the protocols of the core studies 
for full details. 
This extension study is planned to collect up to four years of long-term safety, tolerability and 
efficacy data of secukinumab in both the fixed interval regimen and the retreatment at start of 
relapse regimen. All subjects completing Week 52 of CAIN457A2304 and Week 40 of 
CAIN457A2307 will be eligible to participate in this extension study. Week 40 of the 
CAIN457A2307 study is the end of maintenance visit (EOM) and is equivalent to the Week 52 
(EOM) of the CAIN457A2304 core study. Therefore, all subjects entering the 
CAIN457A2304E1 study will have received 52 weeks of treatment in their previous study / 
studies.   The Week 52 (CAIN457A2304) and Week 40 (CAIN457A2307) of the two core 
studies will together be referred to as “the EOM visit” (end of maintenance visit for the core 
studies) in this protocol. 
In this extension study, the prefilled syringe (PFS) liquid formulation of secukinumab will be 
used. 
This study may be affected by agency review or potential product approval considerations, 
whereby if the product is approved during study conduct dose groups in this proposed extension 
trial may be amended (via a future protocol amendment) based on eventual agency 
recommendations for product usage in this indication. 
1.2 
Purpose  
The purpose of this extension study is to assess long-term safety and maintenance of efficacy 
in two different treatment regimens, a “fixed dose” regimen and a “retreatment at start of 
relapse” regimen.  Within each regimen, two different doses are used: 150 and 300 mg s.c. 
secukinumab.  A successful response is defined as a PASI 75, and subjects who meet this 
criterion are referred to as “responders”.   A PASI 75 responder is a subject achieving ≥ 75% 
improvement (reduction) in PASI score compared to baseline of the core study.   


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Subjects who complete the extension study will provide up to approximately 4 years of 
additional data to the CAIN457A2304 and CAIN457A2307 core studies, which will be 
submitted as supplemental information to support the appropriate individualized use of 
secukinumab for the treatment of moderate to severe, chronic, plaque-type psoriasis.   
Subjects who finished the treatment period in studies CAIN457A2304 or CAIN457A2307 and 
show a meaningful response (as assessed by the investigator and subject) will be enrolled into 
this extension study to allow them to continue treatment with secukinumab, which will not yet 
be commercially available at the time of enrollment. 
2 
Study objectives 
2.1 
Primary and key secondary objectives 
To assess long-term safety and tolerability of secukinumab in subjects with moderate to severe 
chronic plaque-type psoriasis who completed treatment in the core studies CAIN457A2304 and 
CAIN457A2307. 
2.2 
Secondary objectives 
• To evaluate the long-term efficacy of 150 mg and 300 mg of secukinumab administered at 
the start of relapse versus fixed interval regimens of 150 mg and 300 mg of secukinumab 
respectively, in subjects with moderate to severe chronic plaque-type psoriasis who are 
PASI 75 responders at Week 12, with respect to PASI 75 response: 
• at Weeks 104 and 156, for subjects in the fixed interval regimens, or 
• at Weeks 92 and 144, for subjects in the retreatment at start of relapse regimen who 
do not require active treatment at Week 92 or 144, respectively, or 
• at Weeks 104 and 156, for subjects in the retreatment at start of relapse regimen who 
do require active treatment at Week 92 or 144, respectively. 
• To evaluate the efficacy of secukinumab treatment regimens in subjects with moderate to 
severe chronic plaque-type psoriasis with respect to PASI 50/75/90/100 and IGA 0 or 1 
response over time.   
• To evaluate the effects of treatment regimens with secukinumab in subjects with moderate 
to severe chronic plaque type psoriasis with respect to PASI score and IGA mod 2011 score 
over time  
• To assess the effects of secukinumab treatment regimens with respect to EQ-5D score over 
time 
• To investigate the effects of treatment regimens with secukinumab in subjects with 
moderate to severe chronic plaque-type psoriasis with respect to changes in DLQI over time 
• To investigate the effects of treatment regimens with secukinumab in subjects with 
moderate to severe chronic plaque-type psoriasis with respect to DLQI 0 or 1 achievement 
over time 


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• To investigate the potential development of immunogenicity against secukinumab 
• To investigate the occurrence of relapses (achieved maximal PASI improvement from 
baseline in core study is reduced by >50%) and rebounds in subjects on secukinumab 
therapy 
2.3 
Exploratory objectives 
• 
 
• To explore the effects of secukinumab with respect to the HAQ-DI in subjects from core 
study CAIN457A2304 with psoriatic arthritis (PsA) at baseline over time  
• 
 
 
3 
Investigational plan 
3.1 
Study design 
This is a multicenter, double-blind and open label, trial in subjects with moderate to severe 
chronic plaque-type psoriasis who completed treatment in the maintenance period of studies 
CAIN457A2304 or CAIN457A2307. It was expected that approximately 740 subjects would 
be enrolled at approximately 130 study sites worldwide. When recruitment was complete, 675 
subjects had been enrolled at 112 sites.    
This extension study consists of four periods: the screening period, the treatment period, and 
two follow-up periods (follow-up and follow up 2). An outline of the visits is presented in 
Figure 3-1, while a detailed visit schedule can be found in Table 6-1. 
Screening Period 
The screening period for the extended maintenance portion of the study is the duration between 
the signing of the informed consent form and enrollment registered with the interactive response 
technology (IRT).  There are no additional requirements for the  treatment period other than 
subjects are required to complete year 1 of the core studies and all assessments at the end of 
maintenance visit (Week 52) of core study CAIN457A2304 or end of maintenance visit (Week 
40) of core study  CAIN457A2307.  Subjects who complete the EOM visit and assessments of 
the core studies and consent to the extension will continue directly into the treatment period of 
this extension study. Subjects must sign the informed consent form (ICF) for the treatment 
period once the core assessments have been completed for Week 52 of the core studies and the 
IRT called to register that the subject completed the core study (CAIN457A2304 or 
CAIN457A2307).  For the purpose of reading and understanding, the ICF can be provided to 
subjects anytime during the core studies, for example, between Week 48 and prior to the dose 
at Week 52 of study CAIN457A2304 (Weeks 36 and 40 from study CAIN457A2307 are 
equivalent to Weeks 48 and 52 of CAIN457A2304).  However, subjects will NOT sign the ICF 
before completing the core studies’ EOM assessments. 


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Note: subjects from CAIN457A2307 started their visits in that study after completing 12 Weeks 
of the CAIN457A2304 core study; therefore, Week 40 of the CAIN457A2307 study is 
equivalent to Week 52 of the CAIN457A2304 and CAIN457A2304E1 studies as regards 
previous treatment duration (i.e., 52 weeks). 
The dose administered at Week 52 is the first dose of the CAIN457A2304E1 treatment period.   
Treatment Period 
The treatment period is defined as Weeks 52 through 260.   
Subjects from the CAIN457A2304 maintenance period will continue the treatment regimen and 
dose that they were assigned to (Fixed interval regimen or Retreatment at start of relapse 
regimen) during the maintenance treatment period of the core study and return for visits every 
four weeks up until Week 156.  Subjects and study personnel will remain blinded during the 
first two years of the treatment period (except for patients in the open label part of the study).  
The last blinded dose of the treatment period is administered at Week 152.   
At Week 156, subjects will be unblinded and will have the option (based on investigator 
judgment) to switch dosing regimens, with the specific options depending on the blinded 
treatment assigned until that point.  Generally, subjects may switch off of the SoR treatment 
regimen to active secukinumab treatment every four weeks, and subjects may switch from 
secukinumab 150 mg s.c. to secukinumab 300 mg s.c.  After Week 156, office visits will only 
be required every 12-16 weeks until Week 260 (End of Treatment period for 
CAIN457A2304E1) unless a subject continues with the SoR treatment regimen.  Specific 
details of the open-label treatment options for unblinded subjects starting at Week 156 are 
described in Section 5.2 and in Table 5-1.   
Subjects from the CAIN457A2307 maintenance period will continue in the treatment regimen 
and dose that they received during the CAIN457A2307 maintenance treatment period (i.e.,  300 
mg sc secukinumab every four weeks), and return for visits every four weeks up until Week 
156.  After Week 156, subjects will continue being treated every four weeks, but will only be 
required to come in for office visits every 12-16 weeks. These subjects were treated open-label 
during the core study, and will continue to be treated open-label during the treatment period of 
CAIN457A2304E1.  The last dose of secukinumab is provided at Week 256, four weeks prior 
to the end of the treatment period. 
Please refer to Section 5.2 for a more detailed description of the treatment arms.  
Subjects who discontinue study treatment prematurely during the treatment period should have 
all Week 260 protocol assessments (EOT) performed approximately four weeks after their last 
dose of secukinumab/secukinumab placebo and then enter the treatment-free follow-up periods 
(follow-up period and follow-up 2 period). 
Follow-up period (for all subjects) 
Subjects who complete the treatment period (the end of the treatment phase visit is at Week 
260) will enter the treatment free follow-up period with the following visits: Week 264 (Follow-
up visit 4, F4), which is 4 weeks post end of treatment period and 8 weeks post last dose), and 
Week 268 (Follow-up visit 8, F8 or End of Follow-up, EOF) which is 8 weeks post end of 


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treatment period and 12 weeks post last dose). Subjects who prematurely discontinue treatment 
should complete all assessment of Week 260 (end of treatment visit) and then enter follow-up 
period with Weeks 264 and 268 visits. 
Subjects within the follow-up period who withdraw from study should  perform Week 268 
assessments (EOF). 
Follow-up 2 period (only for subjects who prematurely discontinued treatment) 
Subjects who have prematurely discontinued treatment prior to the end of treatment phase 
(Week 260), and completed the Week 260 visit and the subsequent follow-up period visits 
(Weeks 264 and 268) should enter the treatment-free follow-up 2 period. Follow-up 2 period 
consists of telephone calls every 3 months and unplanned assessments e.g. unscheduled 
physical examinations, vital signs and laboratory assessments at the site if investigator considers 
this necessary. The end of Follow-up 2 period (EOF2) for an individual subject will be after 4 
years from the time when subject has been enrolled into the CAIN457A2304E1 study (Figure 
3.1). 
Subjects within the follow-up 2 period who withdraw from study will be recorded in the End of 
Follow-up 2 (EOF2) completion eCRF page. 
 


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Figure 3-1 
Study design 
 
 
3.2 
Rationale of study design 
This four year (208 weeks), multicenter, double-blind and open label, extension study will 
collect long-term efficacy, safety and tolerability of secukinumab in the fixed dose and start of 
relapse treatment regimens.  The randomization to the treatment arms occurred in the core 
studies and is carried over into this extension study. 
The total study duration of four years will allow for assessment of long term safety and efficacy 
in subjects treated for up to five years when combined with data from the core studies. The 
regular assessments of disease activity and clinical status ensure that safety is monitored closely, 
and that both subject and investigator have the opportunity to assess if the continued 


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participation of the subject in the study is to the subject’s benefit. If the subject’s participation 
is deemed not to be of benefit to the subject, the subject can discontinue study treatment at any 
time. 
Subjects who complete the extension study will provide up to approximately 4 additional years 
of long-term safety, tolerability and efficacy data, to the CAIN457A2304 core study.  
Subjects who finished the treatment period in studies CAIN457A2304 or CAIN457A2307 and 
show a meaningful response (as assessed by the investigator and subject) will be enrolled into 
this extension study to allow them to continue treatment with secukinumab, which is not yet 
commercially available at the time of enrollment. 
3.3 
Rationale of dose/regimen, route of administration and duration 
of treatment 
The doses and regimens selected for the secukinumab phase III program were based on phase 
II trial data.   As of the trial initiation, there has not been any data to date to indicate that the 
doses used in the core studies should be modified.  Therefore, this extension study will continue 
treatment with secukinumab s.c. doses of 150 mg and 300 mg administered every four weeks, 
and/or at start of relapse (following the randomization that was done during the core studies) 
for an additional 208 weeks.  This will provide long-term secukinumab efficacy and safety data 
pertaining to the treatment of subjects suffering from chronic plaque-type psoriasis for up to a 
total of 5 years when combined with the core studies data. 
The pivotal phase III trials were analyzed while this extension trial was ongoing and results of 
protocol CAIN457A2304 showed that the re-treatment at start of relapse maintenance regimen 
(SoR) was not non-inferior to a fixed interval regimen (FI) with treatment every four weeks and 
subjects experience better efficacy with 300 mg secukinumab s.c. every four weeks compared 
to 150 mg secukinumab s.c. every four weeks with similar safety profile between the two doses. 
Therefore, at Week 156 all patients treated with the SoR treatment regimen are given the option 
to switch to treatment with active secukinumab every four weeks, and patients treated with 
secukinumab 150 mg s.c. are given the option to switch to treatment with secukinumab 300 mg 
s.c.  Any switches in treatment regimen or dose are to be made according to the investigator’s 
judgment as the investigator will have three years of experience with the subject and the 
subject’s individual response to secukinumab.    
The switch from the lyophilisate to the more convenient prefilled syringe (PFS) is supported by 
the results of the clinical study CAIN457A2106, which has shown that the exposure and safety 
profiles of both formulations are highly comparable. 
3.4 
Rationale for choice of comparator 
This extension study uses the same treatments that were assigned during the core 
CAIN457A2304 and CAIN457A2307 studies.  Therefore, no comparators are used. 
3.5 
Purpose and timing of interim analyses/design adaptations 
One interim analysis is planned for this study.  At time of marketing authorization submission 
of the AIN457A project, the safety data of this extension study will be reported. Since the core 
studies have been unblinded at that stage, this interim analysis will also be unblinded. Of note, 


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investigators, subjects and site staff will remain blinded to individual treatment group 
assignments.  
Further interim analyses, as regarded appropriate, might be conducted (e.g., to provide 
additional data for regulatory or publication purposes). 
When each subject in the study has either completed treatment period and follow-up period, or  
discontinued treatment and completed follow-up and follow-up 2 periods  (last telephone 
contact), or withdrawn from study, the final database lock occurs.  
3.6 
Risks and benefits 
Non-clinical studies have not shown any impediment to using secukinumab administered 
subcutaneously in man.  Study CAIN457A2304E1 will use secukinumab drug substance 
solution in a PFS formulation; biocomparability of secukinumab in PFS and lyophilized 
formulations has been demonstrated (study CAIN457A2106), with highly comparable 
pharmacokinetic properties. 
At the time of Amendment 1, over 6200 subjects with a variety of autoimmune diseases have 
received secukinumab.  Details of the risk and benefits are outlined in the current version of the 
Investigator Brochure. 
The risk to subjects in this trial will be minimized by compliance with the inclusion/exclusion 
criteria, proper study design, and close clinical monitoring. 
In this extension study, CAIN457A2304E1, all subjects will receive active treatment, either 
every four weeks regardless of clinical symptoms, or after they have experienced start of  
relapse. To ensure a double-blind design, some subjects will receive placebo at certain visits, 
according to their treatment group.  For example, patients in the core study CAIN457A2304 
who were randomized to and continue on the retreatment at start of relapse regimen who have 
not experienced a start of relapse will continue on placebo medication until they meet the start 
of relapse criteria. 
All quality, non-clinical pharmacology and toxicology data, as well as the available clinical 
efficacy and safety data, are considered sufficient to expect a positive benefit / risk ratio for the 
treatment of psoriasis with secukinumab, and therefore to initiate this extension study 
CAIN457A2304E1. 
4 
Population 
The study population will consist of a representative group of male and female outpatients (≥ 
18 years old) with moderate to severe chronic plaque-type psoriasis who completed the full 
study treatment period (52 weeks) in the core studies CAIN457A2304 or CAIN457A2307 
(Week 40 in study CAIN457A2307 is equivalent to a total of 52 weeks of treatment with 
secukinumab). 
Study CAIN457A2304 randomized 970 subjects. Assuming that 5% of the subjects drop-out 
up to Week 12, and further 15% drop-out in CAIN457A2304 or CAIN457A2307 it is estimated 
that about 740 subjects will be eligible to enter this study. When recruitment was complete, 675 
subjects had been enrolled at 112 sites. 


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4.1 
Inclusion criteria 
Subjects eligible for inclusion in this study have to fulfill all of the following criteria: 
1. Subjects 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 according to local laws and regulations. 
2. Subjects who complete Week 52 of study CAIN457A2304 or complete Week 40 of study 
CAIN457A2307  
3. Subjects expected to benefit from participation in the extension study, as assessed by the 
subject and investigator 
4.2 
Exclusion criteria 
Subjects fulfilling any of the following criteria are NOT eligible for inclusion in this study: 
1. A protocol deviation in the core studies which according to the investigator will prevent 
the meaningful analysis of the extension study for the individual subject 
2. Ongoing use of prohibited psoriasis or non-psoriasis treatments. Time period from last use 
of prohibited treatments in the core study to first dose of study drug in this extension study 
detailed in Table 5-4 must be adhered to. 
3. Subjects expected to be exposed to an undue safety risk if participating in the trial 
4. Current severe progressive or uncontrolled disease which in the judgment of the 
investigator renders the subject unsuitable for the trial 
5. Plans for administration of live vaccines during the study period 
6. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female 
after conception and until the termination of gestation, confirmed by a positive hCG 
laboratory test (>10 mIU/mL). 
7. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unwilling to use effective contraception during the study and for 16 
weeks after stopping treatment. Effective contraception is defined as either: 
• Barrier method: Condom or occlusive cap (diaphragm or cervical/vault caps) with 
spermicide (where available). Spermicides alone are not a barrier method of 
contraception and should not be used alone  
The following methods are considered more effective than the barrier method and are also 
acceptable: 
• Total abstinence: When this is in line with the preferred and usual lifestyle of the 
subject (Periodic abstinence [e.g. calendar, ovulation, symptothermal, post-
ovulation methods] and withdrawal are not acceptable methods of contraception) 
• Female sterilization: have had a surgical bilateral oophorectomy (with or without 
hysterectomy) or tubal ligation at least six weeks before taking study treatment. 
In case of oophorectomy alone, only when the reproductive status of the woman 
has been confirmed by follow up hormone level assessment  


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• Male partner sterilization (at least 6 months prior to screening). For female 
subjects on the study, the vasectomised male partner should be the sole partner 
for that subject  
• Use of established oral, injected or implanted hormonal methods of 
contraception, intrauterine device (IUD) or intrauterine system (IUS) 
NOTE: Women are considered post-menopausal and not of child bearing potential if they 
have had: 
• 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile (e.g. age appropriate, history of vasomotor symptoms) or  
• six months of spontaneous amenorrhea with serum FSH levels >40 mIU/mL [for 
US only: and estradiol <20 pg/mL] or 
• surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation 
at least six weeks before taking study treatment. In case of oophorectomy alone, 
only when the reproductive status of the woman has been confirmed by follow up 
hormone level assessment is she considered not of child bearing potential. 
No additional exclusion criteria may be applied by the investigator, in order to ensure that the 
study population will be representative of all eligible subjects. 
5 
Treatment 
The blind will be maintained for subjects rolling over from the core CAIN457A2304 study into 
the CAIN457A2304E1 extension study until Week 156.  At Week 156, all patients who rolled 
over from the core CAIN457A2304 study will be unblinded and subjects treated according to 
the SoR regiment will have the option to switch to treatment with active secukinumab every 
four weeks, and subjects treated with secukinumab 150 mg s.c. are given the option to switch 
to treatment with secukinumab 300 mg s.c.  Details of these switch options are provided in 
Section 5.2. 
Subjects from CAIN457A2307 are treated open label and will continue to receive the same 
treatment (300 mg s.c. every four weeks) in the CAIN457A2304E1 extension study. 
All of the packaging for the treatments in this study will be packaged to maintain the blind.  
There will not be any syringes or boxes labeled in an open-label manner as the IRT will be 
responsible for assigning the appropriate medication numbers to each subject.  Although the 
labels on the treatments will not indicate active, the investigator and subjects from the 
CAIN457A2307 core study will know that the content of the PFSs that are assigned to these 
subjects during the CAIN457A2304E1 study are active since the subjects will receive the same 
treatment that they were assigned to during the maintenance period of the core studies.  Also, 
after Week 156, although the labels on the treatment assigned to the subjects from the 
CAIN457A2304 will not indicate active or placebo treatment, the investigator and subjects will 
know what they are being treated with due to the unblinding at Week 156. 


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5.1 
Protocol requested treatment 
5.1.1 
Investigational treatment 
Novartis will supply the following study treatment: 
1. Investigational treatment: Secukinumab 150 mg/1 mL solution for injection is 
provided in PFS for s.c. administration. The 150 mg/1 mL solution in PFS is used for 
both the s.c.150 mg dose (1 syringe) and s.c. 300 mg dose (2 syringes). For blinding 
purposes the subjects in the 150 mg treatment group will also receive one syringe of 
placebo 150 mg. 
2. Placebo secukinumab 150 mg/1 mL solution for injection is provided in PFS for s.c. 
administration. It contains a mixture of inactive excipients, matching the composition 
of secukinumab 150 mg. 
Secukinumab 150 mg/1 mL and placebo secukinumab 150 mg/1 mL is labeled as AIN457 150 
mg/1 mL/Placebo. 
5.1.2 
Additional study treatment 
No additional treatment beyond investigational treatment is requested for this trial. 
5.2 
Treatment arms 
Subjects will continue in the treatment arm that they were assigned to during the 
CAIN457A2304 core study or the CAIN457A2307 core study until Week 156.  At Week 156, 
subjects who rolled over from the CAIN457A2304 core study will be unblinded and may switch 
to one of the treatment options described below according to investigator judgment; subjects 
who rolled over from the CAIN457A2307 core study will continue being treated with 
secukinumab 300 mg s.c. every four weeks. Treatment arms in this study may be affected by 
agency review or potential product approval considerations, whereby if the product is approved 
during study conduct, dose groups in this proposed extension trial may be amended (via a future 
protocol amendment) based on eventual agency recommendations for product usage in this 
indication. 
The study treatment will be provided in individual boxes that contain secukinumab or placebo 
PFS sealed in a plastic wrapper.  Each study treatment box consists of actual PFS and a safety 
device type X100L 
.  The safety syringe is provided with a needle guard 
system that will aid protection from accidental needle sticks. 
Double-blind treatment arms for subjects entering from the CAIN457A2304 core 
study 
During the core study CAIN457A2304, within each treatment regimen, subjects were assigned 
to either the 150 or 300 mg s.c. secukinumab in PFS, thus resulting in four treatment arms 
overall which will be maintained until Week 156: 
Fixed-time interval regimen – “FI”: either 150 or 300 mg s.c. secukinumab in PFS:  In the 
treatment period subjects will receive the same dose they received during the maintenance 
period of the CAIN457A2304 core study. Thus, secukinumab 150 mg subjects will continue to 


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receive 150 mg secukinumab every four weeks, and secukinumab 300 mg subjects will continue 
to receive 300 mg secukinumab every four weeks, from Week 52 up to and including Week 
152. 
Retreatment at start of relapse regimen – “SoR” “start of relapse”: either 150 or 300 mg s.c. 
secukinumab in PFS: “Start of relapse” will be defined as a loss of ≥20% of the maximum PASI 
gain achieved during the CAIN457A2304 or CAIN457A2304E1 study, compared to baseline 
of the CAIN457A2304 study, and a loss of PASI 75 response.  Whenever a subject fulfills the 
start of relapse criteria, active secukinumab will be administered at their scheduled visits (i.e., 
every four weeks) until the subject is back to PASI 75 response, at which point in time they will 
start receiving placebo again. The dose administered in the treatment period of this extension 
study (secukinumab 150 mg or 300 mg in PFS) will be identical to the dose that these subjects 
received during the maintenance period of the CAIN457A2304 core study. If a subject does not 
fulfill the criteria of a start of relapse or is back to PASI 75 response after a start of relapse, they 
will receive placebo PFS injections (two injections per dose) to maintain the blind. This 
treatment regimen is applied every four weeks, from Week 52 up to and including Week 152. 
At Week 156, patients from the maintenance period of the CAIN457A2304 core study will be 
unblinded and continue in the study on one of the treatment options in Table 5-1 according to 
investigator judgment for their assigned treatment arm. 
Table 5-1 
Open-label treatment options starting at Week 156 
Previous treatment arm through 
Week 152 (Unblinded at Week 
156) 
Treatment options, as decided by the 
investigator 
New office visit 
frequency 
Secukinumab 300 mg FI 
Continue secukinumab 300 mg FI 
Every 12-16 weeks 
Secukinumab 300 mg SoR 
Continue secukinumab 300 mg SoR 
for remainder of the study  
Every 4 weeks 
 
OR Switch to secukinumab 300 mg 
dosed every 4 weeks 
Every 12-16 weeks 
Secukinumab 150 mg FI 
Continue secukinumab 150 mg FI 
Every 12-16  weeks 
 
OR Switch to secukinumab 300 mg 
dosed every 4 weeks  
Every 12-16  weeks 
Secukinumab 150 mg SoR 
Continue secukinumab 150 mg SoR 
for remainder of the study 
Every 4 weeks 
 
OR Switch to secukinumab 300 mg 
dosed every 4 weeks  
Every 12-16  weeks 
Open-label treatment arm for subjects entering from the CAIN457A2307 core 
study 
Secukinumab 300 mg s.c. in PFS regimen arm: Each subject to continue receiving two s.c. 
injections of 150 mg secukinumab in PFS every four weeks.  Doses will be administered from 
Week 52 up to and including Week 256. 


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Overview of treatment schedule according to treatment arm 
The treatment details for each treatment arm for Week 52 through Week 152 are highlighted in 
Table 5-2 below.  The treatment details for each treatment assignment for Week 156 through 
Week 256 are highlighted in Table 5-3 below. 
Table 5-2 
Overview of treatment between Week 52 and Week 152 
Treatment arm 
Double-blinded A2304 subjects: 
 Week 52  to   Week 152   
Open-label A2307 subjects:  
Week 52  to  Week 152  
secukinumab 150 
mg fixed interval 
1 s.c. secukinumab 150 mg PFS 
injection + 
1 s.c. PBO secukinumab PFS 
injection 
N/A 
secukinumab 300 
mg fixed interval 
2 s.c. secukinumab 150 mg PFS 
injections 
2 s.c. secukinumab 150 mg PFS 
injections  
secukinumab 150 
mg at start of 
relapse 
At start of relapse and until PASI 75 is 
regained: 
1 s.c. secukinumab 150 mg PFS 
injection + 
1 s.c. PBO secukinumab PFS 
injection 
N/A 
Otherwise: 
2 s.c. PBO secukinumab PFS 
injections 
N/A 
secukinumab 300 
mg at start of 
relapse 
At start of relapse and until PASI 75 is 
regained: 
2 s.c. secukinumab 150 mg PFS 
injections  
N/A 
Otherwise: 
2 s.c. PBO secukinumab PFS 
injections 
N/A 
PBO = placebo; PFS=pre-filled syringe 
Table 5-3 
Overview of treatment between Week 156 and Week 256 
Assigned treatment 
Treatment delivered and frequency of office visits 
secukinumab 150 mg fixed interval 
1 s.c. secukinumab 150 mg PFS injection every four weeks 
Office visits required every 12-16 weeks 
secukinumab 300 mg fixed interval/ 
every four weeks 
2 s.c. secukinumab 150 mg PFS injections every four weeks 
Office visits required every 12-16 weeks 
secukinumab 150 mg at start of 
relapse 
1 s.c. secukinumab 150 mg PFS injection every four weeks 
upon meeting SoR criteria and until PASI 75 is regained; no 
treatment otherwise 
Office visits required every 4 weeks 
secukinumab 300 mg at start of 
relapse 
2 s.c. secukinumab 150 mg PFS injection every four weeks 
upon meeting SoR criteria and until PASI 75 is regained 
No treatment otherwise 


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Assigned treatment 
Treatment delivered and frequency of office visits 
Office visits required every 4 weeks 
5.3 
Treatment assignment 
Patients will continue receiving study treatment as per their treatment arm in the core studies 
(i.e., CAIN457A2304 or CAIN457A2307) until Week 156. The randomization numbers will be 
generated using the following procedure to ensure that treatment assignment is concealed from 
patients and investigator staff. A randomization list will be produced by or under the 
responsibility of Novartis Drug Supply Management using a validated system that automates 
the random assignment of treatment arms to randomization numbers in the specified ratio.  
At the end of Week 52 of CAIN457A2304 (or Week 40 of CAIN457A2307), the investigator 
will complete core study assessments, enter the PASI response into the eCRF and register the 
completion of core study visit in the IRT. The Week 52 of CAIN457A2304 (or Week 40 of 
CAIN457A2307) visit in the core study is the randomization visit for CAIN457A2304E1. 
Based on the fulfillment of inclusion/exclusion criteria by the subject and IRT notification from 
the database of core studies at Week 52 (explained above), the investigator (or designee) will 
call the IRT set up of CAIN457A2304E1. The randomization number will be adopted from core 
study (CAIN457A2304 and CAIN457A2307) in this extension study and IRT will only specify 
a unique medication number for the first package of investigational treatment to be dispensed 
to the patient. The randomization number will not be communicated to the caller and the 
treatment assignment will be unbiased and concealed from patients and investigator staff. 
The randomization list from the core study CAIN457A2304 or CAIN457A2307 will be adopted 
for this extension study. A separate medication list will be produced by or under the 
responsibility of Novartis Drug Supply Management using a validated system that automates 
the random assignment of medication numbers to packs containing the investigational drug(s). 
At Week 156, all subjects will be unblinded and will continue with one of the treatment options 
described in Section 5.2 based on their previous treatment arm and the investigator’s judgment.  
The investigator should select the best option from the options based on the assigned treatment 
up to that point.  This selection should be based on knowledge of and experience with the 
patient. 
5.4 
Treatment blinding 
Subjects, investigator staff and persons performing the assessments will remain blind to the 
identity of the treatment, for subjects who participated in the core CAIN457A2304 study, from 
the time of enrollment in the extension study until Week 156, using the following methods:  
(1) Randomization data from the core study are kept strictly confidential until the time of 
unblinding, and will not be accessible by anyone else involved in the study  
(2) The identity of the treatments will be concealed by the use of investigational treatments that 
are identical in packaging, schedule of administration and appearance. Unblinding will only 
occur in the case of subject emergencies (see Section 5.5.11).  
In order to maintain the blind for the subjects coming from study CAIN457A2304, placebo 
PFSs are used. 


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Subjects participating from the CAIN457A2307 core study, as well as investigator staff, 
persons performing the assessments and data analysts will be unblinded to the treatment that 
these subjects are receiving throughout the duration of this extension study. 
In addition, the bioanalyst will have access to the randomization lists from the core study to 
facilitate analysis of pharmacokinetic samples. The bioanalyst will keep the information 
confidential.  
5.5 
Treating the patient 
5.5.1 
Patient numbering 
Each patient is uniquely identified by a Subject Number which is composed by the site number 
assigned by Novartis and a sequential number assigned by the investigator. Once assigned to a 
patient, the Subject Number will not be reused. The Subject Number is maintained from the 
core study/ studies in the extension. 
Upon signing the informed consent form, the investigator or his/her staff will contact the IRT 
and provide the requested identifying information for the patient to register them into the IRT. 
The site should select the CRF book with a matching Subject Number from the EDC system to 
enter data.  
If the patient fails to be treated for any reason, the IRT must be notified within two days that 
the patient was not treated. The reason for not being treated will be entered on the Screening 
Epoch Study Disposition CRF. 
5.5.2 
Dispensing the investigational treatment 
Each study site will be supplied by Novartis with investigational treatment in packaging of 
identical appearance. 
The investigational treatment packaging has a two-part label. A unique randomization number 
is printed on each part of this label which corresponds to one of the 5 treatment arms and a 
specific visit. Investigator staff will identify the investigational treatment package(s) to dispense 
to the patient by contacting the IRT and obtaining the medication number(s). Immediately 
before dispensing the package 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 subject number.  
5.5.3 
Handling of study treatment 
5.5.3.1 
Handling of investigational treatment 
Investigational treatment must be received by a designated person at the study site, handled and 
stored safely and properly, and kept in a secured location to which only the investigator and 
designees have access. Upon receipt, all investigational treatment should be stored according 
to the instructions specified on the labels. Clinical supplies are to be dispensed only in 
accordance with the protocol. 
Medication labels will be in the local language and comply with the legal requirements of each 
country. They will include storage conditions for the investigational treatment but no 


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information about the patient except for the medication number. The investigator must maintain 
an accurate record of the shipment and dispensing of investigational treatment in a drug 
accountability log. Monitoring of drug accountability will be performed by the field monitor 
during site visits and at the completion of the trial. At the conclusion of the study, and as 
appropriate during the course of the study, the investigator will return all unused investigational 
treatment, 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. 
Handling of other study treatment 
Not applicable. 
5.5.4 
Instructions for prescribing and taking study treatment 
Prefilled syringes are packaged as one syringe per box.  Until Week 156, each subject will 
require two boxes of PFSs per dose. 
• One secukinumab 150 mg PFS and one placebo secukinumab PFS (150 mg dose) 
OR  
• Two secukinumab 150 mg PFS (300 mg dose) OR  
• Two placebo secukinumab 150 mg PFS (Placebo dose for subjects in the SoR 
regimen, who have not relapsed)  
After Week 156, subjects with site visits every 12-16 weeks will be expected to perform home 
administrations at the protocol specified time points (every 4 weeks) when there is no correlated 
office visit.  In these cases, the investigator will dispense, via IRT, the appropriate number of 
investigational treatment packages for the planned home administrations until the next expected 
site visit and detach the outer part of the label from the packaging prior to giving the package 
to the subject.  The subjects will record the date(s) of administration at home and will return the 
used medication and packaging at their next site visit.  Subjects will be asked to return all unused 
medication and packaging at the latest by the completion of the study or discontinuation of 
investigational treatment.  Site staff will record the dates of administration on the appropriate 
documents.   
All study treatment kits assigned to the subject during the study will be recorded / databased in 
the IRT. 
The syringes with the ready-to-use study treatment solution (PFS) will be provided by the site 
staff during the study visit. 
The first study treatment administration will occur at Week 52 (enrollment into the extension) 
after all study scheduled assessments have been performed (and inclusion / exclusion criteria 
confirmed) and only after the scheduled blood samples have been drawn.  It is preferred that 
the subject self-inject the treatment during the site visit, however, if a subject is not able or not 
willing to self-administer, administration will be performed by study site staff.  If the subject is 
not able or not willing to self-administer the PFS at home, he/she may come into the site for 
dosing every 4 weeks. 


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For subjects willing to self-inject, the first use at enrollment visit (Week 52) will take place 
under guidance and the supervision of one site staff member. At the enrollment visit (Week 52) 
the site staff will walk subjects through the “Instructions For Use” on how to self-inject via 
PFS.  At the following visits, subjects will receive the PFS and instructions at the study site to 
follow on their own. 
NOTE: The needle cover of the syringe contains dry rubber (latex), which should not be handled 
by persons sensitive to this substance. 
During the treatment period from Week 52 until Week 256, subjects will receive a maximum  
of 104 study treatment injections (2 injections of secukinumab 150 mg PFS and/or placebo PFS 
at each visit).  The actual number of study treatment injections will depend on the treatment 
assigned.  All subjects will receive 52 study treatment injections between Week 52 and Week 
152 (2 injections of secukinumab 150 mg PFS and/or placebo PFS at each visit); between Week 
156 and 256 subjects could receive as many as 52 study treatment injections (2 injections of 
secukinumab 150 mg PFS every four weeks) or as few as 0 study treatment injections (SoR 
treated subjects who do not meet start of relapse criteria at any point). 
At study visits when pre-dose blood samples have to be drawn (Table 6-1), the study treatment 
will be injected to the subject only after the blood samples have been taken.  
At each visit, all study assessments, including the completion of Patient Reported Outcomes 
(PROs), should be completed prior to the self injection of study treatment. 
After Week 256, no further study treatment will be administered during the treatment period. 
In addition, no study treatment is administered during the follow-up period and follow-up 2 
period. 
The subject should be instructed to contact the investigator if he/she is unable for any reason to 
attend a study visit as scheduled.  
All dates, times of injections, mode of injection (self or by study site staff) during the study 
must be recorded on the Dosage Administration Record eCRF.  Immediately before dispensing 
the package for injection, 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 subject’s unique 
subject number. 
The investigator should promote compliance by instructing the subject to attend the study visits 
as scheduled and by stating that compliance is necessary for the subject’s safety and the validity 
of the study. 
Administration 
Secukinumab solution for s.c. injection or placebo secukinumab solution (active or placebo, 
respectively) will be provided in a PFS. 
The study treatment solution must be injected in non-affected areas of the skin. If possible, 
throughout the trial administer the study treatment to one of the following body regions, 
changing the injection site from visit to visit: right thigh, left thigh, right stomach, left stomach, 
upper outer arm (when assisted by attendant). 


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Prior to administration the boxes containing the PFS with study treatment solution should be 
allowed to come to room temperature unopened for about 20 minutes before administration. 
Used PFS should be disposed immediately after use in a sharps container OR according to the 
regulatory needs of the respective countries. 
Home administration 
After Week 156 (two years of self-administered study treatment under the supervision of site 
staff), subjects will be expected to self-administer the PFS at home when they are not visiting 
the site for any other trial related procedure. Subjects must be instructed to contact the 
investigator/site staff prior to any self-administration if they have any AEs or SAEs to report. 
The subjects will be allowed to self-administer treatment at home only if they have exhibited 
correct self-administration of the PFS at the site.  If the subject is not able or not willing to self-
administer the PFS, he or she should visit the site every 4 weeks, according to the visit schedule, 
and the staff or subject will administer the study drug at the site.  However, during those visits 
no other assessments will be performed other than checking vitals (recorded in source) and 
checking for AEs or SAEs. 
5.5.5 
Permitted dose adjustments and interruptions of study treatment 
Other than the protocol-specified dosing-changes at Week 156, no dose adjustments or 
interruptions are permitted.  
A positive urine pregnancy test during the treatment periods of the study requires immediate 
interruption of study treatment until serum β-hCG is performed and found to be negative. If the 
serum β-hCG test is positive, the subject must be discontinued from the trial. 
5.5.6 
Rescue medication 
Rescue medication is not permitted in this study. 
5.5.7 
Concomitant treatment 
The investigator must consider the baseline and ongoing concomitant treatment in the core 
studies CAIN457A2304 or CAIN457A2307 at Week 52 before a subject enrolls in the extension 
study (CAIN457A2304E1).   
The investigator should instruct the subject to notify the study site about any new treatments 
he/she takes after the start of study treatment. All medications and significant non-drug 
therapies (including physical therapy and blood transfusions) administered after the subject 
started study treatment must be listed on the Concomitant medications eCRF or Surgeries and 
Medical Procedures eCRF. Start date, end date, unit, frequency, route and reason for 
administration or change are to be recorded. 
The investigator should instruct the patient to notify the study site about any new medications 
he/she takes after the patient was enrolled into the study. All medications, procedures and 
significant non-drug therapies (including physical therapy and blood transfusions) administered 
after the patient was enrolled into the study must be recorded. 


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5.5.8 
Prohibited Treatment  
The use of concomitant medication for psoriasis in all body regions (except face, scalp, and/or 
genitoanal area as noted below) is restricted to bland emollients (not supplied by Novartis) and 
other non-medicated interventions. Use of bland emollients must be recorded on the 
Concomitant medications 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. 
The use of bland emollients should be avoided during the 12 hours preceding a scheduled study 
visit. 
Topical corticosteroid (CS) treatment, or use of other topical treatment that is likely to impact 
signs and symptoms of psoriasis, is not allowed for treatment of psoriasis, except when applied 
to the face, scalp, and/or genitoanal area for ≤14 consecutive days. Topical corticosteroid use 
for indications other than psoriasis not on an area affected with psoriasis is allowed for ≤14 
consecutive days. 
Subjects need to be advised to limit exposure to ultraviolet (UV) light (including sunbathing 
and/or use of UV tanning devices) during the study to avoid possible effect on psoriasis. 
The investigator should instruct the subject to notify the study site about any new treatments 
he/she takes after the start of the study treatment.  All prohibited medications and significant 
non-drug therapies administered after the subject starts treatment with study treatment must be 
listed on the Concomitant medications eCRF or the Surgeries and Medical Procedures eCRF. 
Use of any treatments displayed in Table 5-4 that could confound the efficacy is NOT allowed 
for any indication during the study excluding treatment-free follow-up 2 period. 
Table 5-4 
Prohibited treatment  
Prohibited treatments†,‡  
Alefacept, briakinumab, efalizumab, ustekinumab 
Biological immunomodulating agents other than above (e.g., adalimumab, etanercept, 
infliximab) 
Other systemic immunomodulating treatments§ (e.g., MTX, cyclosporine A, 
corticosteroids§, cyclophosphamide) 
Other systemic psoriasis treatments* (e.g. retinoids, fumarates) 
Photochemotherapy (e.g., PUVA) 
Phototherapy (e.g., UVA, UVB) 
Use of topical treatment that is likely to impact signs and symptoms of  psoriasis for > 14 
consecutive days*  (e.g., corticosteroids [CS], vitamin D analogues, pimecrolimus, 
retinoids, salicylvaseline, salicylic acid, lactic acid,  tacrolimus, tar, urea, α-hydroxy or fruit 
acids) 
Live virus vaccinations during extension study 


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Prohibited treatments†,‡  
Any investigational treatment or participation in any interventional clinical trial during 
extension trial 
†If a subject inadvertently used the prohibited treatment in the core study (e.g. CAIN457A2304 or 
CAIN457A2307) without undue safety risk till completion of Week 52, eligibility will need to be 
discussed with the global clinical team.  
‡In case of undue safety risk for the subject, the subject should discontinue study treatment at the 
discretion of the investigator. If the subject received a live virus vaccination during the study, the 
subject must discontinue study treatment. 
§Inhalative CS with only a topical effect (e.g., to treat asthma) are not considered “systemic 
immunomodulating treatments” and are therefore acceptable as co-treatment 
*There is no restriction on the use of anti-histamines or the use of corticosteroids in the eye or ear. 
5.5.9 
Discontinuation of study treatment and premature patient withdrawal 
Subjects may voluntarily withdraw from the study for any reason at any time. They may be 
considered withdrawn if they state an intention to withdraw, fail to return for visits, or become 
lost to follow-up for any other reason. 
Discontinuation from a treatment period  
If premature withdrawal occurs for any reason, the investigator must make every effort to 
determine the primary reason for a subject’s premature withdrawal from the study and record 
this information on the end of treatment (EOT) eCRF (Week 260). 
Study treatment must be discontinued under the following circumstances: 
• Withdrawal of informed consent 
• Emergence of the following adverse events: adverse events that in the judgment of the 
investigator, taking into account the subject’s overall status, prevent the subject from 
continuing participation in the study (for example, sepsis or serious infection).  
• Any laboratory abnormalities that in the judgment of the investigator, taking into  
consideration the subject’s overall status, prevents the subject from continuing 
participation in the study. 
• Pregnancy (see Section 6.5.6 and Section 7.4) 
• Continued use of prohibited treatment as per recommendations in Table 5-4. 
• Any other protocol deviation that results in a significant risk to the subject’s safety 
In addition to the requirements mentioned above for study treatment discontinuation, the 
investigator should discontinue study treatment for a given subject if, on balance, he/she 
believes that continuation would be detrimental to the subject’s well-being. 
Subjects who discontinue study treatment should NOT be considered withdrawn from the study. 
These subjects should have all Week 260 protocol assessments performed approximately four 
weeks after their last dose of secukinumab and then enter the treatment-free follow-up period 
(Weeks 264 and 268). Subsequently, these subjects should enter the follow-up 2 period. On the 
EOT eCRF (Week 260), the site staff must record the date and primary reason for stopping 
study treatment. 


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The investigator must contact the IRT when the subject completes the assessments on Week 
260 due to study treatment discontinuation. 
Study treatment must be discontinued after emergency unblinding. 
The appropriate personnel from the study site and Novartis will assess whether study treatment 
should be discontinued for any subject whose treatment code has been broken inadvertently for 
any reason. 
See Section 6 for the required assessments of these subjects after study treatment 
discontinuation. 
Withdrawal from a treatment-free period 
If premature withdrawal occurs for any reason in the treatment-free follow up period or follow-
up 2 period, the investigator must make every effort to determine the primary reason for a 
subject’s premature withdrawal from the study and record this information on the applicable 
end of study period eCRF (Follow-up period completion eCRF [Week 268] or Follow-up 2 
period completion eCRF, respectively). 
Patients who withdraw from the follow-up period should perform the Week 268 assessments 
(see Table 6-1). 
Premature subject withdrawal 
Subjects who state an intention to withdraw prematurely from the study will be asked to return 
for follow-up visits to assess safety after cessation of therapy and, if willing, to assess duration 
of effect (e.g. rebound assessments). If the subject returns to the study site to have his/her 
follow-up visits, the investigator will follow the study treatment discontinuation procedures. 
The investigator must contact the IRT when the subject completes the assessments on visit of 
Week 260 to register the subject’s early completion of the study due to subject withdrawal. 
Lost to follow-up 
For subjects who are lost to follow-up (i.e. those subjects 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 documenting in the source documents steps taken to contact the 
subject, e.g. dates of telephone calls, registered letters, etc. 
5.5.10 
Emergency breaking of treatment assignment 
Emergency treatment code breaks should only be undertaken when it is essential to treat the 
patient safely and efficaciously. Most often, study treatment discontinuation and knowledge of 
the possible treatment assignments are sufficient to treat a study patient who presents with an 
emergency condition. Emergency treatment code breaks are performed using the IRT. When 
the investigator contacts the system to break a treatment code for a patient, he/she must provide 
the requested patient identifying information and confirm the necessity to break the treatment 
code for the patient. The investigator will then receive details of the investigational drug 
treatment for the specified patient and a fax or email confirming this information. The system 


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will automatically inform the Novartis monitor for the site and the global study lead that the 
code has been broken. 
It is the investigator’s responsibility to ensure that there is a procedure in place to allow access 
to the IRT  in case of emergency. The investigator will inform the patient how to contact his/her 
backup in cases of emergency when he/she is unavailable. The investigator will provide 
protocol number, investigational treatment name if available, patient number, and instructions 
for contacting the local Novartis CPO (or any entity to which it has delegated responsibility for 
emergency code breaks) to the patient in case an emergency treatment code break is required at 
a time when the investigator and backup are unavailable. 
Study treatment must be discontinued after emergency unblinding. 
The appropriate personnel from the study site and Novartis will assess whether study treatment 
should be discontinued for any subject whose treatment code has been broken inadvertently for 
any reason. 
Subjects who are prematurely unblinded will be discontinued from the study treatment and 
requested to return for the end of the treatment period visit (Week 260) , two follow-up visits 
and follow-up 2 period as described in Section 3.1. 
5.5.11 
Study completion and post-study treatment 
• 
A subject entering into CAIN457A2304E1 will be said to have completed the extension 
study after he/she has completed all visits and assessments as defined in Table 6-1 and 
received all doses of the study treatment in accordance with the protocol.  
• 
The extension study as a whole will be considered complete when all eligible subjects 
rolled over from the core study (e.g., CAIN457A2304 or CAIN457A2307) have 
completed as per protocol the visits and assessments defined in Table 6-1 for study 
CAIN457A2304E1. 
The investigator also must provide follow-up medical care for all subjects who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care. Subjects who 
complete CAIN457A2304E1 may be eligible to enter another planned extension trial. 
5.5.12 
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 properly managed for a prematurely 
withdrawn patient. 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 IRBs and/or ECs of the early termination of 
the trial. 
6 
Visit schedule and assessments 
Table 6-1 Assessment Schedule lists all of the assessments and indicates with an “x” when the 
visits are performed. 


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Subjects should be seen for all visits on the designated day within the allowed “visit window” 
specified below or as close to it as possible. 
During the treatment period, subjects may be seen at an unscheduled visit, e.g. if they 
experience deterioration of psoriasis, or AEs that in the opinion of the investigator need 
intervention or repeated laboratory testing. During these unscheduled visits, study treatment 
will NOT be administered. A visit window of “±5” will be allowed for Week 52 to Week 260 
during the treatment period during the follow-up period or as close to it as possible. 
Subjects who discontinue study treatment will continue to be followed for safety assessments. 
They are not considered withdrawn from the study.   
Subjects who discontinue study treatment before completing the study, and those who 
prematurely withdraw from the study for any reason should be scheduled for a study visit 4 
weeks after their last study treatment administration, at which time all the assessments listed 
for EOT (Week 260) will be performed (see Section 5.5.10). Subjects will return to the study 
site for further assessments as indicated under the follow-up visits (Weeks 264 and 268) (see 
Section 3.1).  
Only subjects who prematurely discontinued study treatment should enter follow-up 2 period 
after completion of follow-up visits (Weeks 264 and 268). Follow-up 2 period includes 
telephone calls every 3 months until 4 years from the time subjects have been enrolled into 
CAIN457A2304E1 as well as potential unplanned assessments e.g physical examinations, vital 
signs and laboratory assessments during this time. 
If they refuse to return for the needed assessments in the follow-up period or are unable to do 
so, every effort should be made to contact them or a knowledgeable informant by telephone or 
by sending appropriate correspondence (i.e. certified letter) immediately. At this contact, the 
safety (e.g., potential occurrence of AE or SAE) and the primary reason for a subject’s 
premature withdrawal should be determined. 
At a minimum, subjects will be contacted for safety evaluations during the 12 weeks following 
the last dose of study treatment, including final contact at the 12-week point. Documentation of 
attempts to contact the subject should be recorded in the subject record. 
Order of assessments: 
• Subject to complete QoL tools prior to any investigator assessments. Order of QoL tools 
is: DLQI, EQ-5D, HAQ-DI (subjects with history of PsA only but not applicable to 
subjects from the CAIN457A2307 core study) 
• Investigator to complete investigator assessments. Order is: 
1. IGA 
2. PASI  
• All remaining study visit procedures (e.g., laboratory sample collection, vital signs 
measurements) must be completed prior to study treatment dosing. 
• Enter PASI and IGA assessments into eCRFs BEFORE contacting IRT at any scheduled 
visit  
• Contact IRT to register the subject visit and receive study drug assignment.  


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Protocol No. CAIN457A2304E1 
Table 6-1 
Assessment schedule 
 
Treatment Period (Years 1 and 2) 
Unscheduled visit 
Week (Relative to Baseline of 
core studies) 
52a 
Core 
52a 
Ext 
56 
60 
64 
68 
72 
76 
80 
84 
88 
92 
96 
100 104 108 112 116 120 124 128 132 136 140 144 
148 
152 
156 
Visit window (in days) 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
 
Day 
365 365 393 421 449 477 505 533 561 589 617 645 673 701 729 757 785 813 841 869 897 925 953 981 1009 1037 1065 1093  
In office visit- all subjects 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
x 
Obtain informed consent 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Continue with Week 160 
 
Inclusion/exclusion criteria1 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
Physical examination 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
(x) 
Weight 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
X 
 
Vital signs 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
Urinalysis (local) 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
X 
 
Lab analysis:  
chemistry and hematology2 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
Fasting Labs: lipid panel2 
x 
 
 
 
 
 
 
x 
 
 
 
 
 
 
x 
 
 
 
 
 
x 
 
 
 
 
 
 
X 
 
Fasting Labs:  
plasma glucose 2 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
X 
 
Serum pregnancy test3  
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x3 
Urine pregnancy test (local)4 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
X 
 
ECG (standard 12 lead) 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
X 
 
Blood sample for IG5,6 
x 
 
 
 
 
 
 
x 
 
 
 
 
 
 
x 
 
 
 
 
 
x 
 
 
 
 
 
 
X 
x5,6 
Blood sample for PK5,6 
x 
 
 
 
x 
 
 
x 
 
 
 
 
 
 
x 
 
 
x 
 
 
x 
 
 
 
 
 
 
X 
x5,6 
PASI 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
 
x 
IGA mod 2011 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
Adverse event (AE) 
assessment 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
EQ-5D 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
X 
 


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Protocol No. CAIN457A2304E1 
 
Treatment Period (Years 1 and 2) 
Unscheduled visit 
Week (Relative to Baseline of 
core studies) 
52a 
Core 
52a 
Ext 
56 
60 
64 
68 
72 
76 
80 
84 
88 
92 
96 
100 104 108 112 116 120 124 128 132 136 140 144 
148 
152 
156 
Visit window (in days) 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
 
Day 
365 365 393 421 449 477 505 533 561 589 617 645 673 701 729 757 785 813 841 869 897 925 953 981 1009 1037 1065 1093  
DLQI 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
X 
 
HAQ-DI8 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
X 
 
Serious AE assessment 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
Completion call for core study  x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete PASI and IGA 
eCRF and call IRT  
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
 
Dispense Investigational 
Treatment 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
X 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 


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Amended Protocol v02 Clean 
 
Protocol No. CAIN457A2304E1 
 
 
 
Treatment Period (Years 3 and 4) 
Unscheduled visit11 
Follow-up 
period 
Follow-
up 2 
Period 
Week (Relative 
to Baseline of 
core studies) 
160 
164 
168 
172 
176 
180 
84 
188 
192 
196 
200 
204 
208 
212 
216 
220 
224 
228 
232 
236 
240 
244 
248 
252 
256 
260 
264 
/F4 
268 
/F8 
Phone 
call 
every 3 
months 
Visit Window (in 
days) 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
 
Days 
1121 1149 1177 1205 1233 1261 1289 1317 1345 1373 1401 1429 1457 1485 1513 1541 1569 1597 1625 1653 1681 1709 1737 1765 1793 1821 
1849 1877 
 
In office visit if 
every 4 wks 
dosing 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
 
 
x 
x 
 
Home 
administration if 
every 4 wks 
dosing 
x 
x 
 
x 
x 
 
x 
x 
 
x 
x 
x 
 
x 
x 
 
x 
x 
 
x 
x 
 
x 
x 
x 
 
 
 
 
 
In office visit if 
SoR dosing 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
x 
x 
x 
 
Concomitant 
medications 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Physical 
examination 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
(x) 
x 
x 
 
Weight 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
 
Vital signs 
O 
O 
x 
O 
O 
x1 
O 
O 
x 
O 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
O 
x 
x 
x 
x 
 
Urinalysis 
(local) 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
Lab analysis:  
chemistry and 
hematology2 
 
 
 
 
 
x 
 
 
 
 
 
 
x 
 
 
 
 
 
x 
 
 
 
 
 
 
x 
x 
x 
x 
 
Fasting Labs:  
lipid panel2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
 
Fasting Labs:  
plasma glucose 
2 
 
 
 
 
 
x 
 
 
 
 
 
 
x 
 
 
 
 
 
x 
 
 
 
 
 
 
x 
 
 
x 
 


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Protocol No. CAIN457A2304E1 
 
Treatment Period (Years 3 and 4) 
Unscheduled visit11 
Follow-up 
period 
Follow-
up 2 
Period 
Week (Relative 
to Baseline of 
core studies) 
160 
164 
168 
172 
176 
180 
84 
188 
192 
196 
200 
204 
208 
212 
216 
220 
224 
228 
232 
236 
240 
244 
248 
252 
256 
260 
264 
/F4 
268 
/F8 
Phone 
call 
every 3 
months 
Visit Window (in 
days) 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
 
Days 
1121 1149 1177 1205 1233 1261 1289 1317 1345 1373 1401 1429 1457 1485 1513 1541 1569 1597 1625 1653 1681 1709 1737 1765 1793 1821 
1849 1877 
 
Serum 
pregnancy test3  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x3 
 
 
 
Urine 
pregnancy test 
(local)4 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
ECG (standard 
12 lead) 
 
 
 
 
 
x 
 
 
 
 
 
 
x 
 
 
 
 
 
x 
 
 
 
 
 
 
x 
 
 
x 
 
Blood sample 
for IG5,6 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
x 
x5,6 
 
x 
 
Blood sample 
for PK5,6 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
 
 
 
 
 
 
 
 
 
 
 
x 
x5,6 
 
x 
 
PASI 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
O 
x 
x 
x 
x 
 
Assessment of 
rebound 
symptoms7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
x7 
x 
x 
 
IGA mod 2011 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
x 
x 
x 
 
Adverse event 
(AE) 
assessment 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
O 
x 
x 
x 
x 
x 
DLQI 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
 
 
HAQ-DI8 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
 
 
x 
 
 
 
x 
 
 
 
 
Serious AE 
assessment 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
O 
x 
x 
x 
x 
x 
Complete PASI 
(and IGA9) 
eCRF and call 
IRT  
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
O 
x 
 
 
 
 


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Amended Protocol v02 Clean 
 
Protocol No. CAIN457A2304E1 
 
Treatment Period (Years 3 and 4) 
Unscheduled visit11 
Follow-up 
period 
Follow-
up 2 
Period 
Week (Relative 
to Baseline of 
core studies) 
160 
164 
168 
172 
176 
180 
84 
188 
192 
196 
200 
204 
208 
212 
216 
220 
224 
228 
232 
236 
240 
244 
248 
252 
256 
260 
264 
/F4 
268 
/F8 
Phone 
call 
every 3 
months 
Visit Window (in 
days) 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
 
Days 
1121 1149 1177 1205 1233 1261 1289 1317 1345 1373 1401 1429 1457 1485 1513 1541 1569 1597 1625 1653 1681 1709 1737 1765 1793 1821 
1849 1877 
 
Dispense 
Investigational 
Treatment 10 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
x 
O 
O 
O 
x 
 
 
 
 
End of 
Treatment 
Period (EOT) 
eCRF and call 
IRT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
 
 
 
Follow-up 
Period 
completion  
eCRF 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
Follow-up 2 
Period 
completion  
eCRF 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
eCRF:electronic case report form; PK:pharmacokinetics; IG:immunogenicity 
O: assessment completed for subjects with protocol-mandated in-office visits in between Week 160 and 256. 
*The screening period will be the duration between signing the informed consent form and enrollment registered with Interactive response technology 
(IRT).  Subjects must sign the informed consent form after completing the core study Week 52 assessments.  
a Enrollment into the extension study occurs on the same day (Week 52) as the end of maintenance period of the core study CAIN457A2304 or 
CAIN457A2307 (±5 days).  The column for Week ‘52 core’ represents assessments that will be done during the CAIN457A2304 core Week 52 visit or the 
CAIN457A2307 Week 40 visit.  These assessments will be entered in the core study eCRFs.  The column Week ’52 ext’ represents assessments that 
will be done for the CAIN457A2304E1 study.   
1These assessments are supported by and are stored with the source documentation. However, data regarding to which Inclusion/Exclusion criteria are 
not met are captured on the Inclusion/Exclusion Screen eCRF. 
2 Samples will be shipped to and analyzed by the central laboratory.  


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Protocol No. CAIN457A2304E1 
3 To be done for female subjects of childbearing potential for whom local urine pregnancy test at end of maintenance period (Week 52) of core study is 
positive. The study drug treatment should not be given until the results confirm that subject is not pregnant. 
4 If there is a positive urine pregnancy test, study treatment must be withheld and a serum pregnancy test must be done at the same visit. 
5 Samples will be shipped by the sites and stored by the central laboratory. Samples will be shipped to reference laboratories for analysis. Each PK and 
IG sample is to be collected pre-dose for visits from Week 52 to Week 256.  
6 An unscheduled IG and or PK sample is collected only to replace an IG or PK sample not taken at a regular scheduled visit. (If an IG sample is taken, a 
PK sample must accompany the IG sample.) 
7 Unscheduled rebound assessment only to be done for an unscheduled visit that occurs during the treatment free follow-up period following a study drug 
discontinuation. 
8  During this extension study, the HAQ-DI is completed only by subjects from core study CAIN457A2304 who have a history of psoriatic arthritis at the 
core baseline visit. 
9 IGA eCRF only needs to be completed at visits when IGA is required 
10 In subjects treated per SoR regiment, investigational treatment should only be dispensed and administered to patients meeting protocol-defined SoR 
treatment criteria 
11 During follow-up 2 period unscheduled visits may include unplanned assessments like physical examinations, vital signs and laboratory assessments if 
investigator considers this necessary. 


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Amendment Protocol v02 Clean 
 
Protocol No. CAIN457A2304E1 
 
 
6.1 
Information to be collected on screening failures 
All subjects who have signed an informed consent but who cannot or chose not to enter the 
CAIN457A2304E1 treatment period will be considered screen failures. If the subject 
discontinues before enrollment, the IRT must be called within two days and the reason for not 
being enrolled will be entered on the Screening Phase Disposition electronic Case Report Form 
(eCRF). The Screening visit date, Informed Consent eCRF, Inclusion/Exclusion Criteria eCRF 
must be completed. If the subject has any SAE in the screening period (between signing the ICF 
and being enrolled), the Adverse Event eCRF and a paper SAE form must be completed.  
If a subject fails to be treated in the extension study, the subject completes the follow-up visits 
in the respective core study. 
The Withdrawal of consent eCRF should be completed if consent was withdrawn during the 
screening period before the subject was enrolled. The Death eCRF should be completed in the 
case of a death during the screening period. 
6.2 
Patient demographics/other baseline characteristics 
The following information will be based on information derived from core study 
CAIN457A2304 or CAIN457A2307.  This information will not be reentered into the 
CAIN457A2304E1 eCRFs. 
Subject demographic and baseline characteristic data to be collected on all subjects include: 
date of birth, age, sex, race, ethnicity, source of subject referral, and on-going concomitant 
medications (relative to core studies) present before signing informed consent for this extension 
study. 
6.3 
Treatment exposure and compliance 
All doses of study treatment administration will be recorded on the appropriate Dosage 
Administration Record eCRF page.  
Compliance will be assessed by Novartis study personnel at each visit using vials counts and 
information provided by the pharmacist or the qualified site personnel. 
6.4 
Efficacy 
All efficacy assessments should be performed prior to administration of study treatment. 
It is important to perform the IGA before the PASI, as the knowledge of PASI scoring can 
potentially influence how the evaluator scores the IGA. Therefore, the following order should 
be applied when performing the efficacy assessments during study visits:  
• Investigator’s Global Assessment (IGA mod 2011; scale from 0 – 4) 
• Psoriasis Area and Severity Index (PASI; score from 0 – 72) 
• Rebound assessment 


Novartis 
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Amendment Protocol v02 Clean 
 
Protocol No. CAIN457A2304E1 
 
 
6.4.1 
Investigator’s global assessment (IGA mod 2011) 
IGA mod 2011 will be conducted for overall psoriatic disease as indicated in Table 6-1.  It is 
recommended that the same evaluator conducts the assessment throughout the study whenever 
possible. 
The IGA mod 2011 rating scale for overall psoriatic disease is shown in Table 6-2 The IGA 
mod 2011 rating scale. 
The IGA mod 2011 scale has been used in the core studies CAIN457A2304 and 
CAIN457A2307, and is a modified version of the scale used in secukinumab phase II studies; 
it was developed in collaboration with health authorities. 
The IGA mod 2011 used in this study is static, i.e. it refers exclusively to the subject’s disease 
state at the time of the assessments, and does not attempt a comparison with any of the subject’s 
previous disease states, whether at baseline or at a previous visit. 
The IGA mod 2011 score will be recorded in the eCRF. 
Table 6-2  
The IGA mod 2011 rating scale  
Score 
Short description 
Detailed description 
0 
Clear 
No signs of psoriasis. Post-inflammatory hyperpigmentation may be 
present. 
1 
Almost clear 
Normal to pink coloration of lesions; no thickening; no to minimal 
focal scaling 
2 
Mild 
Pink to light red coloration; just detectable to mild thickening; 
predominantly fine scaling 
3 
Moderate 
Dull bright red, clearly distinguishable erythema; clearly 
distinguishable to moderate thickening; moderate scaling 
4 
Severe 
Bright to deep dark red coloration; severe thickening with hard 
edges; severe / coarse scaling covering almost all or all lesions 
Note: Involvement of nails is not part of the assessment. 
Based on this scale, a subject will be considered as IGA 0 or 1 responder if the subject achieves 
a score of 0 or 1 and improved by at least two points on the IGA scale compared to baseline. 
6.4.2 
Assessment of the psoriasis area and severity index (PASI) 
The investigator or qualified designee will complete the PASI assessment as indicated in Table 
6-1. Whenever possible, the same evaluator should perform this assessment at all visits. 
A PASI score (Fredriksson and Pettersson 1978, Weisman et al 2003, Gottlieb et al 2005) will 
be derived as indicated in Table 6-3. 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 four 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 help the assessment: 
1. The neck is assessed as part of the head. 


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Protocol No. CAIN457A2304E1 
 
 
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. 
Table 6-3 
The PASI scoring system 
Body region 
Erythema  (E) 
Thickening     
(plaque elevation, 
induration, I) 
Scaling 
(desquamation) 
(D) 
Area score 
(based on true 
area %, A)* 
Head (H)** 
0=none 
1=slight 
2=moderate 
3=severe 
4=very severe 
0=none 
1=slight 
2=moderate 
3=severe 
4=very severe 
0=none 
1=slight 
2=moderate 
3=severe 
4=very severe 
0 = 0% 
1 = 1-9% 
2 = 10-29% 
3 = 30-49% 
4 = 50-69% 
5 = 70-89% 
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 = 0% 
1 = 1-9% 
2 = 10-29% 
3 = 30-49% 
4 = 50-69% 
5 = 70-89% 
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 = 0% 
1 = 1-9% 
2 = 10-29% 
3 = 30-49% 
4 = 50-69% 
5 = 70-89% 
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 = 0% 
1 = 1-9% 
2 = 10-29% 
3 = 30-49% 
4 = 50-69% 
5 = 70-89% 
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. 


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Protocol No. CAIN457A2304E1 
 
 
****Buttocks are assessed as part of the Lower limbs (L) body region. 
Because the head and neck, upper limbs, trunk and lower limbs correspond to approximately 
10%, 20%, 30% and 40% of the body surface area, 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 6-3. 
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 investigator is only responsible for collecting the components or scoring signs and total 
regional area. PASI calculations, including changes over time will be done by Novartis via the 
PASI Score eCRF. At Week 52 and every visit throughout the extension study, the investigator 
or qualified designee should ensure that all the information required for the PASI calculation 
was entered into the PASI Score eCRF and that a PASI score is available prior to contacting 
IRT.  The start of relapse status will be automatically calculated in the PASI score eCRF for the 
specific visit. Based on the start of relapse status, IRT will assign a medication number. This 
will be transmitted to the pharmacist for the preparation of the appropriate study treatment to 
be administered to the subject.  
Definitions of efficacy variables based on PASI 
The following definitions are used in this study (see CHMP guidelines for psoriasis 
(CHMP/EWP/2454/02 2004)), baseline referring to randomization visit in CAIN457A2304: 
• PASI 50 response: subjects achieving ≥ 50% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 50 responders  
• PASI 75 response: subjects achieving ≥ 75% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 75 responders 
• PASI 90 response: subjects 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) 
• Relapse: when the achieved maximal PASI improvement from baseline is reduced 
by >50% 
• In addition to the above, the following definition is also used in this protocol: 
• Start of relapse: loss of  ≥20% of the maximum PASI gain in CAIN457A2304 or 
CAIN457A2304E1 (compared to baseline of the core study) achieved at any time before 
the visit at which the assessment is made and loss of PASI 75 response 
• PASI Partial response: Subjects achieving at least 50%, but less than 75% reduction of 
PASI compared to baseline (i.e PASI 50 but not a PASI 75 response) 
• PASI Non response: Subjects achieving less than 50% reduction of PASI compared to 
baseline 


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6.4.2.1 
Assessment of rebound 
Rebound of disease will be assessed as indicated in Table 6-1. 
In addition, to the assessment of PASI, the investigator will assess whether new pustular 
psoriasis, or new erythrodermic psoriasis, or more inflammatory psoriasis occurred (yes/no). 
6.4.3 
Appropriateness of efficacy assessments  
PASI scores outcome measures, the assessment of the severity of the psoriasis symptoms and 
the extent to which the subject’s body area is affected by the disease, is mandated by the EMA 
for psoriasis (CHMP guideline on the treatment of psoriasis-CHMP/EWP/2454/02 2004). 
6.5 
Safety 
All blood draws and safety assessments should be done prior to study treatment administration. 
Appropriate safety assessments (e.g. evaluation of AEs and SAEs including injection site 
reactions) should be repeated after the dose is administered. 
• Evaluation of all AEs and SAEs including injection site reactions  
• Physical examination 
• Vital signs 
• Laboratory evaluations 
• Hematology 
• Clinical chemistry 
• Urinalysis 
• Immunogenicity (assessment of anti-secukinumab antibody development) 
• Electrocardiogram  
• Pregnancy and assessments of fertility 
For frequency of assessments, see Table 6-1 
6.5.1 
Physical examination 
A physical examination, including general appearance, skin, neck, eyes, ears, nose, throat, 
lungs, heart, abdomen, back, lymph nodes, extremities, vascular and neurological systems will 
be performed as indicated in Table 6-1. 
If possible, assessments for an individual subject 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 signing of the informed consent form 
will have been already entered during core study in the Medical History screen on the subject’s 
eCRF. Significant findings made after signing informed consent which meet the definition of 
an Adverse Event must be recorded on the Adverse Event screen of the subject’s eCRF (Section 
7). 


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6.5.2 
Vital signs 
Vital signs (including blood pressure and pulse measurements) will be assessed at every 
scheduled visit as indicated in Table 6-1.  
After the subject has been sitting for five 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.  In case the cuff 
sizes available are not large enough for the subject's arm circumference, a sphygmomanometer 
with an appropriately sized cuff may be used (Mancia et al 2007). On the Vital Signs eCRF, the 
average of the two measurements will be entered. 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 ≥140 mmHg and/or diastolic ≥ 90 mmHg) 
or hypotension (systolic <90 mmHg and/or diastolic <60 mmHg). A blood pressure indicative 
of prehypertension (systolic 120 to < 140 mmHg and/or diastolic 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 under the measurement conditions outlined above. Notable pulse rates 
are a rate below 60 bpm (bradycardia) or above 100 bpm (tachycardia). 
The investigator will decide whether action needs to be taken to address notable vital signs, 
taking into account the overall status of the subject. No specific action is foreseen as part of the 
study protocol. 
6.5.3 
Height and weight 
Height and weight will be based on information derived from core study CAIN457A2304 or 
CAIN457A2307.  This information will not be reentered into the CAIN457A2304E1 eCRFs at 
Week 52 (enrollment) and body weight will be measured as listed in Table 6-1. 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 
Subjects should avoid smoking within the hour preceding the blood draws. A central laboratory 
will be used for analysis of all specimens listed below, 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. Refer the Laboratory Manual for identification of 
laboratory reference range values and the schema for notification of site staff and Novartis for 
out of range values. 
Appendix 1 shows the extended laboratory ranges that are considered clinically notable. 
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 subject. No specific action is foreseen 
as part of the study protocol. 


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6.5.4.1 
Hematology 
Hemoglobin, hematocrit, red blood cell count, white blood cell count with differential 
(neutrophils including bands, lymphocytes, monocytes, eosinophils, basophils) and platelet 
count will be measured at all scheduled study visits, within the visit window specified in Table 
6-1. 
6.5.4.2 
Clinical chemistry 
Serum chemistries will include urea, creatinine, total bilirubin, AST (SGOT), ALT 
(SGPT),GGT, alkaline phosphatase, sodium, potassium, bicarbonate, calcium, phosphorous, 
total protein, albumin, and uric acid. Serum chemistries will be measured at all scheduled study 
visits within the visit window specified in Table 6-1. 
6.5.4.3 
Urinalysis 
Dipsticks will be provided by the central laboratory to the study sites for local urinalysis 
assessments. The sites will record the results in the appropriate eCRF page for each subject. 
Standard dipstick measurements for specific gravity, protein, glucose, pH, blood, urine blood 
dipstick (non-hemolyzed), urine blood dipstick (hemolyzed), bilirubin, ketones and WBC will 
be done at scheduled visits as indicated in Table 6-1. 
6.5.4.4 
Immunogenicity (IG) 
Blood samples for IG (anti-secukinumab antibodies) will be taken pre-dose at the scheduled 
timepoints as indicated in Table 6-1 and Table 15-2. Blood samples (approximately 2 mL) will 
be collected into serum separator tubes (SST). The blood sample will be allowed to clot over a 
minimum of 30 minutes at room temperature prior to harvesting of the serum. The serum will 
be obtained by centrifugation at approximately 2500 revolutions per minute (rpm) for 10 
minutes. 
Serum samples will be placed on ice, split into 2 aliquots (labeled plain barrier polypropylene 
tubes) and then stored (within 30 minutes of collection) at approximately -70°C to -20°C prior 
to shipment on dry ice to the central laboratory. Shipment of stored aliquots from the site to the 
central lab should be on a monthly basis. To the extent possible, the site should send each aliquot 
to the central laboratory separately. If a study site does not have the facility to store aliquots at 
the conditions specified, then they will maintain the sample on dry ice at the site and ship on 
dry ice on the day of collection. 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 lab as a backup 
sample. Remaining samples will only be disposed of after approval by the global study lead 
(typically 6 to 12 months after the clinical study report [CSR] is published). 
All blood samples will be taken by direct venipuncture. The actual sample collection date and 
exact time of collection will be entered on the Blood collection for IG eCRF or the unscheduled 
blood collection for IG eCRF, as appropriate. Sampling problems will be noted in the ‘Reason 
sample not taken’ section of the eCRF. 
A laboratory manual will be provided by the central laboratory with detailed information on 
sample collection, sample handling and shipment. 


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Tubes and labels will be provided by the central laboratory with study/sample type and sample 
number preprinted on the label. 
Further details on labeling of the IG samples can be found in Appendix 4, Section 16.1.1 
6.5.5 
Electrocardiogram (ECG) 
A standard 12-lead ECG will be performed as indicated in Table 6-1. At each visit when an 
ECG is done, the investigator must review and initial the tracing. The tracing must then be 
stored with the subject's source documents. 
All ECGs must be performed on the ECG machines provided to the study site. 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. 
Even though there is no exclusion criterion specifically based on the ECG, clinically significant 
findings from the ECG assessment made at Week 52 of the core study must be discussed with 
the Novartis Medical Monitor prior to enrolling the subject in the extension study. 
If the ECG findings are clinically relevant and would prevent the subject from participating in 
the study (taking into account the subject's overall status as well as the medication profile), the 
subject should not receive study treatment. 
6.5.6 
Pregnancy and assessments of fertility 
A serum β-hCG test will have already been performed on all women of child-bearing potential 
who entered studies CAIN457A2304 and CAIN457A2307. 
All women of child-bearing potential who are eligible to participate in this extension study will 
have a local urine pregnancy test as indicated in Table 6-1. If positive, they will undergo a 
serum pregnancy evaluation conducted at the Central Laboratory 
Any woman whose resulting pregnancy test is positive (based on serum β-hCG as defined by 
the Central Laboratory) at the Enrollment Visit Week 52 will have to discontinue from this 
extension study and return to the follow-up assessments in the core study. 
A positive urine pregnancy test during the treatment periods of the study requires immediate 
interruption of study treatment until serum β-hCG is performed and found to be negative. If the 
serum β-hCG test is positive, the subject must be discontinued from the trial (as per Section 
5.5.10) 
6.5.7 
Appropriateness of safety measurements 
The safety measures used in this study are reliable and relevant standard measures for a biologic 
immunomodulating agent in psoriasis. 
6.6 
Other assessments 
These include (as indicated in Table 6-1) 
• Fasting laboratory evaluations,  
• Health-related quality of life assessments such as 
1. DLQI 


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2. EQ-5D 
3. HAQ-DI (only in subjects with psoriatic arthritis from study CAIN457A2304, not 
CAIN457A2307) 
• PK assessments will be done as indicated in Table 6-1.  
 
6.6.1 
Fasting laboratory evaluations 
Fasting (8 hour duration with water ad libitum) laboratory tests will be assessed as indicated in 
Table 6-1. 
Subjects should avoid smoking within the hour preceding the blood draws. 
A central laboratory will be used for analysis of all fasting laboratory specimens. Details of the 
collections, shipment of samples and reporting of results by the central laboratory are provided 
to the investigators in the Laboratory Manual. 
6.6.1.1 
Plasma glucose 
Fasting plasma glucose will be taken as a fasting blood sample at scheduled visits as indicated 
in Table 6-1. 
6.6.1.2 
Lipid panel 
A lipid profile including High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), 
cholesterol, triglycerides, lipoprotein (a), apolipoprotein B, apolipoprotein A-1, and adiponectin 
will be measured from a fasting blood sample at scheduled visits as indicated in Table 6-1. 
6.6.2 
Resource utilization 
Not applicable 
6.6.3 
Health-related Quality of Life 
The impact of psoriasis on various aspects of subject’s health-related quality of life will be 
assessed by the following validated instruments: 
• Dermatology Life Quality Index (DLQI©) 
• EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D©) 
• Health Assessment Questionnaire- Disability Index (HAQ©-DI) (subjects with PsA from 
study CAIN457A2304 only) 
At the appropriate scheduled visits (see Table 6-1), questionnaires are to be completed by each 
subject in the language with which she/he is most facile, and before she/he sees the Investigator 
for clinical assessments. Responses will be collected using digitized paper with a digital pen. 
The digitized paper will serve as source documentation; the pen will be transferred to its 
docking station for transmittal of the subject’s responses to the vendor’s database. Subjects are 
to complete the “Patient Reported Outcome (PRO) - Completion confirmation by the patient” 
page after completing all the questionnaires of a visit. This document will not be sent to the 
sponsor but kept at site in source documents. 


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The subject is to be given sufficient space and time to complete the questionnaires. The study 
coordinator is to check the questionnaires for completeness and encourage the subject to 
complete any missing responses. The original questionnaires will be kept with the subject’s file 
as source documentation.  
Completed questionnaires will be reviewed and examined by a blinded staff member at the site 
(not the Investigator or evaluator of the subject for the physician assessments), before the 
clinical examination, for responses that may indicate potential AEs or SAEs. The Investigator 
is to review not only the responses to the questions in the questionnaires but also to look for 
unsolicited comments written by the subject. If AEs or SAEs are confirmed by the Investigator, 
then she/he must record the events as per instructions given in Section 7 of the protocol. 
Investigators and study coordinators are not to encourage subjects to change the responses 
reported in the completed questionnaires. Study coordinators are to complete the header 
information at the top of the questionnaire prior to distributing it to the subjects. 
6.6.3.1 
Dermatology Life Quality Index (DLQI) 
The Dermatology Life Quality Index (DLQI) is a 10-item general dermatology disability index 
designed to assess health-related quality of life in adult subjects with skin diseases such as 
eczema, psoriasis, acne, and viral warts (Finlay and Khan, 1994). 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 
32 different skin conditions and is available in 55 languages. The recall period is the last week, 
and the instrument requires 1 to 2 minutes for completion. Each item has four 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 and higher scores indicate greater health-related quality-of-life impairment. Additionally, 
each subscale of the DLQI may be analyzed separately.  
The DLQI questionnaire (date of publication 1994) will be completed by the subject as indicated 
in Table 6-1. 
6.6.3.2 
EuroQOL 5-Dimension (EQ-5D©) Health Status Questionnaire 
EQ-5D© is a generic instrument to assess each subject’s health status. It provides a simple 
descriptive profile and a single index value for health status. The instrument essentially consists 
of 2 pages – the EQ-5D© descriptive system and the EQ visual analog scale (VAS). The EQ-
5D© descriptive system comprises the following 5 dimensions: mobility, self-care, usual 
activities, pain/discomfort and anxiety/depression. 
Each dimension has 3 response levels: no problems, some problems, severe problems. The 
subject is asked to indicate her/his health state by ticking (or placing a cross) in the box against 
the most appropriate statement in each of the 5 dimensions. 
The VAS records the respondent’s self-rated health on a vertical scale 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. 


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The EQ-5D© questionnaire (date of publication 1990) is to be completed by the subject at the 
visits indicated in Table 6-1. 
6.6.3.3 
Health Assessment Questionnaire- Disability Index (HAQ©-DI) 
(subjects with PsA only) 
The Health Assessment Questionnaire (HAQ©) was developed by Stanford University and is 
one of the most widely used measures to assess the long-term influence of chronic disease on a 
subject's level of functional ability and activity restriction. Although originally developed for 
use in subjects with rheumatic disease, the HAQ has been employed across a large variety of 
disease areas. The disability assessment component of the HAQ (Health Assessment 
Questionnaire© – Disability Index), the HAQ-DI, assesses a subject's level of functional ability 
and includes questions of fine movements of the upper extremity, locomotor activities of the 
lower extremity, and activities that involve both upper and lower extremities. There are 20 items 
in eight categories of functioning including dressing & grooming, arising, eating, walking, 
hygiene, reach, grip, and usual activities. The stem of each item asks over the past week "Are 
you able to …" perform a particular task. Each item is scored on a 4-point scale from 0 to 3, 
representing normal (without any difficulty [0]), with some difficulty (1), with much difficulty 
(2), and unable to do (3). The HAQ-DI also includes questions about the use of ‘aids or devices’ 
and aid from other people to supplement the answers given to the 20 items.  
The purpose of the HAQ-DI in this study is to provide long-term information on the functional 
ability of psoriasis subjects that also suffer from psoriatic arthritis. 
The HAQ-DI questionnaire will be completed by the subject as indicated in Table 6-1 by all 
subjects with a medical history of PsA recorded on the Psoriatic Arthritis History eCRF during 
the screening period of the CAIN457A2304 core study (subjects from the CAIN457A2307 
study will not participate in the HAQ-DI questionnaire). 
6.6.4 
Pharmacokinetics 
At all study sites, blood samples will be collected for PK at the scheduled visits as indicated in 
Table 6-1. 
For a detailed description of the blood sampling schema, including time points, refer to the 
Blood Log in Appendix 3, Table 15-1.  
All blood samples will be taken by direct venipuncture. Blood samples (approximately 2 mL, 
not less than 1.5 mL) will be collected into SST tubes. The blood sample will be allowed to clot 
over a minimum of 30 minutes at room temperature prior to harvesting of the serum. The serum 
will be obtained by centrifugation at approximately 2,500 rpm for 10 minutes. 
Serum samples will be placed on ice, split into 2 aliquots (polypropylene tubes) and then stored 
(within 30 minutes of collection) 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 
monthly basis. To the extent possible, the site should send each aliquot to the central laboratory 
separately. If a study site does not have the facility to store aliquots at the conditions specified, 
then samples must be stored on dry ice at the site and shipped on dry ice on the day of collection. 
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 lab as a backup sample. Remaining samples will 


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only be disposed of after approval by the global study lead (typically 6 to 12 months after the 
Clinical study report (CSR) is published). 
The actual sample collection date and exact time of collection will be entered on the Blood 
collection for PK eCRF or the Unscheduled blood collection for PK eCRF, as appropriate. 
Sampling problems will be noted in the ‘Reason sample not taken’ section of the eCRF. 
PK sample handling, labeling and shipment instructions 
A laboratory manual will be provided by the central laboratory 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. 
Further details on labeling of the pharmacokinetics samples can be found in Appendix 4, 
Section 16.1.1 
PK sample stability 
 
AIN457 is stable in serum samples for 4 months at -20°C or at -80°C. Longer stability 
assessment is ongoing. 
PK analytical methods 
An ELISA method will be used for bioanalytical analysis of AIN457 in serum, with an 
anticipated lower limit of quantification (LLOQ) of 80 ng/mL. The detailed method description 
to assess AIN457 concentration will be described in the bioanalytical raw data of the study and 
in the respective BDR. 
 
 
 
 
 
 
 
 
 
 
 
6.6.6 
Other biomarkers 
Not applicable. 


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7 
Safety monitoring 
7.1 
Adverse events 
An adverse event (AE) is any untoward medical occurrence (i.e., any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or 
clinical investigation subject 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. 
The occurrence of adverse events should be sought by non-directive questioning of the patient 
at each office visit or each telephone call 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. Subjects must be instructed to contact the 
investigator/site staff prior to any self-administration of study drug if they have any AEs or 
SAEs to report. 
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria: 
• they induce clinical signs or symptoms,  
• they are considered clinically significant,  
• they require therapy.  
Clinically significant abnormal laboratory values or test results should be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline or the previous visit, or values which are considered to be non-typical in patient with 
underlying disease. Investigators have the responsibility for managing the safety of individual 
patient and identifying adverse events. Alert ranges for labs and other test abnormalities are 
included in Appendix 1. 
Adverse events should be recorded in the Adverse Events CRF under the signs, symptoms or 
diagnosis associated with them accompanied by the following information. 
• the severity grade  
• mild: usually transient in nature and generally not interfering with normal activities 
• moderate: sufficiently discomforting to interfere with normal activities 
• severe: prevents normal activities 
• its relationship to the (select what is applicable) 
study treatment (no/yes), or 
investigational treatment (no/yes), or  
the other study treatment(non-investigational) (no/yes), or 
both or indistinguishable, 
• its duration (start and end dates) or if the event is ongoing an outcome of not 
recovered/not resolved should be reported. 
• whether it constitutes a serious adverse event (SAE)  
• action taken regarding investigational treatment  


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• whether other medication or therapies have been taken (concomitant medication/non-drug 
therapy) 
• its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown) 
An SAE is any adverse event (appearance of (or worsening of any pre-existing) undesirable 
sign(s), symptom(s) or medical conditions(s) which meets any one of the following criteria  
• 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: 
• routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
• 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  
• 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  
• social reasons and respite care in the absence of any deterioration in the patient’s 
general condition 
• is medically significant, i.e. defined as an event that jeopardizes the patient or may require 
medical or surgical intervention to prevent one of the outcomes listed above. 
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. 
Unlike routine safety assessments, SAEs are monitored continuously and have special 
reporting requirements; see Section 7.2. 
All adverse events should be treated appropriately. Treatment may include one or more of the 
following: no action taken (i.e. further observation only); [study/investigational] (select) 
treatment dosage adjusted/temporarily interrupted; study drug(s) permanently discontinued; 
concomitant medication given; non-drug therapy given. The action taken to treat the adverse 
event should be recorded on the Adverse Event CRF.  
Once an adverse event 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 investigational treatment, 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 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 adverse event (beyond the 
protocol observation period) that the patient, or the patient’s personal physician, believes might 


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reasonably be related to study treatment. This information should be recorded in the 
investigator’s source documents, however, if the AE meets the criteria of an SAE, it must be 
reported to Novartis. 
7.2 
Serious adverse event reporting 
To ensure patient safety, every SAE, regardless of causality, occurring during  following time 
periods must be reported to Novartis within 24 hours of learning of its occurrence:  
• after the subject has provided informed consent and until 12 weeks after the last 
administration of study treatment or 30 days after the subject has stopped the study 
participation (defined as last visit of the study at Week 268) for subjects who don’t 
enter follow-up 2 period  
• after the subject has provided informed consent and until the last telephone contact for 
patients who enter follow-up 2 period  
Any SAEs experienced after these periods should only be reported to Novartis if the investigator 
suspects a causal relationship to study treatment. 
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 Serious Adverse Event Report Form or the electronic Serious Adverse 
Event Form within the OC/RDC system (where available). The Investigator must assess the 
relationship to each specific component of the study treatment (if the study treatment consists 
of several components).  
SAEs (initial and follow-up) that are recorded on the paper SAE form should be faxed within 
24 hours of awareness of the SAE to the local Novartis Drug Safety and Epidemiology 
Department.  The telephone and fax number of the contact persons in the local department of 
Drug Safety and Epidemiology, specific to the site, are listed in the investigator folder provided 
to each site.  The original copy of the SAE Report Form and the fax confirmation sheet must be 
kept with the case report form documentation at the study site. Follow-up information should 
be provided using a new paper SAE Report Form stating that this is a follow-up to a previously 
reported SAE   
SAEs (initial and follow-up) that are recorded electronically in the OC/RDC system should be 
entered, saved and e-signed within 24 hours of awareness of the SAE or changes to an 
existing SAE. These data will automatically be submitted to Novartis Drug Safety & 
Epidemiology 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 


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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 investigational treatment 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 investigational 
treatment 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 Directive 2001/20/EC 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 two categories: 
• Liver events of special interest (AESI) which consist of LFTs elevations 
• Medically significant liver events which are considered as serious adverse events (SAEs) 
and which consist of marked elevations of LFTs and / or pre-specified adverse events. 
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 or designated personal at the trial site as summarized below. Detailed information 
is outlined in Table 14-2 in Appendix 2. 
• Repeating the LFT to confirm elevation as appropriate 
• Discontinuation of the investigational drug if appropriate 
• Hospitalization of the patient if appropriate 
• A causality assessment of the liver event via exclusion of alternative causes (e.g., 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, 
hepatologist’s consultancy, based on investigator’s discretion. All follow-up information, and 
the procedures performed should be recorded on appropriate CRF pages, including the liver 
event overview CRF pages. 
7.4 
Pregnancy reporting 
To ensure subject safety, each pregnancy occurring while the patient is on study treatment must 
be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 


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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 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 treatment 
Any SAE experienced during pregnancy must be reported on the SAE Report Form. 
7.5 
Prospective suicidality assessment 
Not applicable.  
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 CRFs 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 on the CRFs, the adherence to the protocol and to Good Clinical 
Practice, the progress of enrollment, and to ensure that study treatment is being stored, 
dispensed, and accounted for according to specifications. Key study personnel must be available 
to assist the field monitor during these visits. 
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, electrocardiograms, and the results of any other tests or 
assessments. All information on CRFs must be traceable to these source documents in the 
patient's file. The investigator must also keep the original informed consent form signed by the 
patient (a signed copy is given to the patient). 
The investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the CRF entries. Novartis monitoring standards require full verification for the 
presence of informed consent, adherence to the inclusion/exclusion criteria, documentation of 
SAEs, and of data that will be used for all primary variables. Additional checks of the 
consistency of the source data with the CRFs are performed according to the study-specific 
monitoring plan. No information in source documents about the identity of the patients will be 
disclosed. 
8.2 
Data collection 
Designated investigator staff will enter the data required by the protocol into the OC/RDC 
system. Designated investigator site staff will not be given access to the system until they have 
been trained.  
Automatic validation procedures within the system check for data discrepancies during and 
after data entry and, by generating appropriate error messages, allow the data to be confirmed 


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or corrected online by the designated investigator site staff. The Investigator must certify that 
the data entered into the electronic Case Report Forms are complete and accurate. After 
database lock, the investigator will receive copies of the patient data for archiving at the 
investigational site.  
8.3 
Database management and quality control 
Novartis staff (or CRO working on behalf of Novartis) review the data entered into the CRFs 
by investigational staff for completeness and accuracy and instruct the site personnel to make 
any required corrections or additions. Queries are sent to the investigational site using an 
electronic data query. Designated investigator site 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 site. Site personnel 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 investigator site. 
Concomitant medications entered into the database will be coded using the WHO Drug 
Reference List, which employs the Anatomical Therapeutic Chemical classification system. 
Concomitant procedures, non-drug therapies and adverse events 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). 
ECG readings will be processed centrally and the results will be sent electronically to Novartis 
(or a designated CRO). 
Randomization codes and data about all study drug(s) dispensed to the patient and all dosage 
changes will be tracked using an Interactive Response Technology (IRT). The system will be 
supplied by a vendor, who will also manage the database. The database will be sent 
electronically to Novartis (or a designated CRO). 
Each occurrence of a code break via IRT will be reported to the clinical team and monitor.  The 
code break functionality will remain available until study shut down or upon request of 
Novartis. 
8.4 
Data Monitoring Committee 
A data monitoring committee (DMC) may review the safety data of this trial at selected time 
intervals. If needed, details regarding the DMC process will be available in relevant 
secukinumab DMC charter. 
8.5 
Adjudication Committee 
Not required. 
9 
Data analysis 
Treatment groups for analysis will include: 
• Secukinumab 150 mg fixed interval 


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• Secukinumab 300 mg fixed interval 
• Secukinumab 150 mg start of relapse 
• Secukinumab 300 mg start of relapse 
• Secukinumab 300 mg open-label 
• Secukinumab 300 mg open-label switch 
9.1 
Analysis sets 
Randomized set: The randomized set will be defined as all subjects who were randomized in 
core studies and who entered this extension study. 
Full analysis set (FAS): The FAS will be comprised of all subjects entered the study. Following 
the intent-to-treat principle, subjects will be analyzed according to the treatment assigned to at 
randomization in core study. If the actual stratum is different to the assigned stratum in IRT, 
the actual stratum will be used in analyses. 
Safety set: The safety set includes all subjects who took at least one dose of study treatment 
during the treatment period. Subjects will be analyzed according to treatment received. 
9.2 
Patient demographics and other baseline characteristics 
Demographics and baseline characteristics 
Summary statistics will be presented for continuous demographic and baseline characteristic 
variables for each treatment group and for all subjects in the randomized set. The number and 
percentage of subjects in each category will be presented for categorical variables for each 
treatment group and all subjects. 
Medical history 
Any significant prior or active medical condition at the time of signing informed consent will 
be coded using the MedDRA dictionary. These medical conditions will be summarized by 
primary system organ class and preferred term. 
To establish a baseline level of cardiovascular risk, the number and percentage of subjects with 
pre-solicited cardiovascular risk factors will be summarized by treatment group. The number 
of cardiovascular risk factors that each subject has will also be summarized by treatment group. 
If it is unknown whether or not a subject currently or previously experienced a specific 
cardiovascular risk factor, it will be assumed that cardiovascular risk factor did not occur for 
that subject. 
Psoriasis specific medical history will be summarized by treatment group. Previous treatments 
for psoriasis and whether or not response was achieved will be summarized by treatment group. 
All the medical history information will be retrieved from the core studies. 


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9.3 
Treatments 
Study treatment 
The analysis of study treatment data will be based on the safety set. 
The duration of exposure to study treatment will also be summarized by treatment group. In 
addition, the number and percentage of subjects with cumulative exposure levels (e.g., any 
exposure, <4 weeks, ≥ 4 weeks, ≥ 8 weeks, etc.) will be presented. 
Prior and concomitant medication 
Prior and concomitant medications will be summarized in separate tables by treatment group. 
Prior medications are defined as treatments taken and stopped prior to first dose of study 
treatment. Any medication given at least once between the day of first dose of randomized study 
treatment and the date of the last study visit will be a concomitant medication, including those 
which were started pre-baseline and continued into the period where study treatment is 
administered. 
Medications will be presented in alphabetical order, by Anatomical Therapeutic Classification 
(ATC) codes and grouped by anatomical main group. Tables will show the overall number and 
percentage of subjects receiving at least one treatment of a particular ATC code and at least one 
treatment in a particular anatomical main group. 
Significant prior and concomitant non-drug therapies and procedures will be summarized by 
primary system organ class and MedDRA preferred term. 
The number and percentage of subjects receiving different classes of prior psoriasis therapy 
(biologic systemic therapy, non-biologic systemic therapy, topical, phototherapy, 
photochemotherapy) will be presented by treatment group as well as the reasons for stopping 
their previous prior psoriasis therapies (primary lack of efficacy, secondary lack of efficacy, 
lack of tolerability, other) and the total duration of exposure to psoriasis therapies previously. 
Prior concomitant medications will be retrieved from the core studies. 
9.4 
Analysis of the primary and key secondary variable(s) 
The primary analysis will focus on safety variables, please refer to Section 9.5.2. There are no 
other key secondary variables assessed in this study. 
9.4.1 
Variable(s) 
Not Applicable 
9.4.2 
Statistical model, hypothesis, and method of analysis 
Not applicable 


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9.4.3 
Handling of missing values/censoring/discontinuations 
Missing values in efficacy analyses, except for maintenance of response will not be imputed. 
All analyses will be based on observed values only. 
For maintenance of response, please see definition below, missing values with respect to 
response variables based on PASI score score will be imputed with non-response regardless to 
the reason for missing data (e.g. premature study discontinuation, missed visit, administrative 
issues). Following the intent-to-treat principle for subjects who prematurely discontinue 
treatment, but who are observed in the follow-up period, efficacy data collected in follow-up 
periods will be linked to planned but missed study visits as well, following imputation schemes 
described in the analysis plan. 
Subjects who opt to change treatment regimen or dose level and move into open-label treatment 
with 300 mg s.c. secukinumab every four weeks for the remainder of the trial will be considered 
as non-responders in the analysis of maintenance of response. 
For other efficacy analyses they will not be considered after the timepoint of switching. 
9.4.4 
Supportive analyses 
Not applicable 
9.5 
Analysis of secondary variables 
9.5.1 
Efficacy variables 
Maintenance of response 
Maintenance of response will be defined analogously as in the primary endpoint in 
CAIN457A2304, but for week 104 and 156, i.e. PASI 75 response 
• at Weeks 104 and 156, for subjects in the fixed interval regimens, or 
• at Weeks 92 and 144, for subjects in the retreatment at start of relapse regimen who do not 
require active treatment at Week 92 or 144, respectively, or 
• at Weeks 104 and 156, for subjects in the retreatment at start of relapse regimen who do 
require active treatment at Week 92 or 144, respectively. 
Summary statistics for maintenance of response at Week 104 and 156 will be presented in 
contingency tables and will include absolute and relative frequencies. Confidence intervals for 
response rates will be derived as well based on the score method including continuity correction 
(Newcombe 1998). 
PASI 50, PASI 75, PASI 90, PASI 100 and IGA 0 or 1 response over time 
Summary statistics for PASI 50, PASI 75, PASI 90, PASI 100 and IGA 0 or 1 response by visit 
will be presented in contingency tables and will include absolute and relative frequencies. 
Confidence intervals for response rates will be derived as well based on the score method 
including continuity correction (Newcombe, 1998). 
PASI score over time 


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Summary statistics will be provided for absolute PASI scores as well as for percent change from 
baseline by visit and treatment group. Figures will also be provided. 
IGA mod 2011 score over time 
Summary statistics for the IGA mod 2011 score over time will be presented by visit and 
treatment group in contingency tables. 
Relapse 
The number and percentage of subjects experiencing relapse will be presented by visit and 
treatment group. 
Rebound 
Rebound is defined as a worsening of PASI of > 125% of the value at baseline (core study), or 
new pustular, erythrodermic or more inflammatory psoriasis occurring within 8 weeks of 
stopping therapy (i.e., if this definition is fulfilled at more than 8 weeks after last study treatment 
administration, this is not defined as rebound). The number and percentage of subjects 
experiencing rebound will be presented by visit and treatment group. 
9.5.2 
Safety variables 
All safety evaluations will be performed on the Safety set.  
Adverse events 
Treatment emergent adverse events are defined as any events started after the first dose of 
study treatment and within 84 days after the last study treatment, or events present prior to the 
first dose of study treatment, but increased in severity based on preferred term within 84 days 
after the last study treatment. 
With the exception of adverse events that qualify as "treatment emergent" (see definition 
above), data collected from telephone visits and unscheduled visits in follow-up period 2 will 
only be included in individual patient listings, but not in summary tables. 
AEs will be summarized by presenting, for each treatment group, the number and percentage 
of subjects having any AE, having an AE in each primary system organ class and having each 
individual AE (preferred term). Summaries will also be presented for AEs by severity and for 
study treatment related AEs. If a subject reported more than one adverse event with the same 
preferred term, the adverse event with the greatest severity will be presented. If a subject 
reported more than one adverse event within the same primary system organ class, the subject 
will be counted only once with the greatest severity at the system organ class level, where 
applicable.  
Confidence intervals for relative frequencies will be derived as well according to the score 
method including continuity correction by Newcombe, 1998. 
Separate summaries will be provided for death, serious adverse event, other significant adverse 
events leading to discontinuation and adverse events leading to dose adjustment (including 
study treatment discontinuation). 
A graphical display of relative frequencies within system organ classes and relative risks, if 
appropriate, will be presented.   


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For infections, time-to-event analysis will be done. Results will be tabulated and the Kaplan-
Meier estimates for the cumulative rate will be plotted.    
Additional analyses will be provided for adjudicated adverse events.   
In supplementary analyses, exposure (or observation)-time adjusted analyses in terms of 
incidence rate and event rate will be provided.   
Laboratory data 
The summary of laboratory evaluations will be presented for three groups of laboratory tests 
(hematology, serum chemistry and urinalysis). Descriptive summary statistics for the change 
from baseline to each study visit will be presented. These descriptive summaries will be 
presented by test group, laboratory test and treatment group. Change from baseline will only be 
summarized for subjects with both baseline and post baseline. 
For each parameter, the maximum change from baseline within each study period will be 
analyzed analogously. 
In addition, shift tables will be provided for all parameters to compare a subject’s baseline 
laboratory evaluation relative to the visit’s observed value. For the shift tables, the normal 
laboratory ranges will be used to evaluate whether a particular laboratory test value was normal, 
low, or high for each visit value relative to whether or not the baseline value was normal, low, 
or high. These summaries will be presented by laboratory test and treatment group for the most 
extreme laboratory value post-baseline.  
Immunogenicity 
Summary statistics for baseline, each post-baseline visit and change from baseline to each visit 
will be provided. Summary statistics will be provided for the percent of subjects with 
immunogenicity. If appropriate, shift tables will also be presented. 
Vital signs 
Analysis of the vital sign measurements using summary statistics for the change from baseline 
for each post-baseline visit will be performed. These descriptive summaries will be presented 
by vital sign and treatment group. Change from baseline will only be summarized for subjects 
with both baseline and post-baseline values. 
ECG 
Summary statistics will be presented for ECG variables by visit and treatment group. 
9.5.3 
Resource utilization 
Not applicable 
9.5.4 
Health-related Quality of Life 
Summaries will be based on the FAS and will be presented separately for study periods (i.e., 
treatment period and follow-up period) if not specified otherwise.  
EQ-5D 
 


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The EQ-5D is a questionnaire with 5 questions (regarding mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression) each with three categories (no problem, moderate 
problem, severe problems) and a health state assessment from 0 (worst possible health state) to 
100 (best possible health state). The number and percentage of subjects in each of the three 
categories for each question will be presented by visit and treatment group. Summary statistics 
will be shown for the health state assessment by visit and treatment group. 
DLQI©   
The DLQI measures functional disability of subjects with dermatological disorders that are 
greater than 18 years of age and had been utilized as a relevant clinical measure in atopic 
dermatitis, as well as other dermatitis clinical trials.  The DLQI is a simple, validated, self-
administered 10-item questionnaire.  The instrument contains six functional scales (i.e., 
symptoms and feeling, daily activities, leisure, work and school, personal relationships, 
treatment).  For the DLQI, each question will be answered with the following response: “not at 
all,” “a little,” “a lot,” or “very much”. Seven scores will be derived from the DLQI: the total 
score of each of the six dimensions as well as the total score over all items. The higher the score, 
the more quality of life is impaired.  
For each of the seven scores the percentage change from baseline will be derived. Summary 
statistics will be provided for absolute values as well as for the percentage change by visit and 
treatment group.  
In addition, summary statistics will be provided for number of subjects achieving DLQI 0 or 1.  
HAQ©-DI (for subjects with PsA at baseline of the core study) 
Summary statistics will be derived for HAQ©-DI score over time for all subjects with psoriatic 
arthritis recorded on the Psoriatic Arthritis History eCRF at screening visit of the core study. 
Absolute and relative frequencies for HAQ©-DI response will also be presented. HAQ©-DI 
response is defined by an improvement of 0.3 score points compared to baseline. 
9.5.5 
Pharmacokinetics 
All completed subjects with quantifiable PK measurements of secukinumab will be included in 
the PK data analysis. Serum concentrations will be expressed in mass per volume units. All 
concentrations below the limit of quantification or missing data will be labeled as such in the 
concentration data listings. PK concentrations will be summarized by visit and treatment group. 
In addition to mean, standard deviation, coefficient of variation, median and quartiles, the 
geometric mean and geometric coefficient of variation and n(log) will be presented.  
   
 
 
 
 
 
 
 
 


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9.5.7 
Biomarkers 
Not applicable. 
9.5.8 
PK/PD 
Not applicable. 
   
9.6 
Interim analyses 
One interim analysis is planned for this study. At time of marketing authorization submission 
of the AIN457A project, the safety data of this extension study will be reported. Since the core 
studies have been unblinded at that stage, this interim analysis will also be unblinded. Of note, 
investigators, subjects and site staff will remain blinded to individual treatment group 
assignments. 
Further interim analyses, as regarded appropriate, can be conducted (e.g., for regulatory or 
publication purposes). 
9.7 
Sample size calculation 
Study CAIN457A2304 planned to randomize 918 subjects. Assuming that 5% of the subjects 
drop-out up to Week 12, and further 15% drop-out in CAIN457A2304 or CAIN457A2307 it is 
estimated that about 740 subjects will be eligible to enter this study. Assuming that the PASI 
75 response rate at Week 12 in CAIN457A2304 is 80% and under the assumed drop-out rates 
above, about 148 subjects of each of the four treatment groups of CAIN45A2304 will be eligible 
to enter this extension study.   
With 148 subjects per treatment group the likelihood to observe at least one occurrence of an 
AE with a crude incidence of 0.1% is about 14% and with a crude incidence of 1% is about 
77%. 
10 
Ethical considerations 
10.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented and reported in accordance with the 
ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local 
regulations (including European Directive 2001/20/EC, US Code of Federal Regulations Title 
21, and Japanese Ministry of Health, Labor, and Welfare), and with the ethical principles laid 
down in the Declaration of Helsinki. 


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10.2 
Informed consent procedures 
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent, or, if incapable of doing 
so, after such consent has been provided by a legally acceptable representative of the patient. 
In cases where the patient’s representative gives consent, the patient should be informed about 
the study to the extent possible given his/her understanding. If the patient is capable of doing 
so, he/she should indicate assent by personally signing and dating the written informed consent 
document or a separate assent form. Informed consent must be obtained before conducting any 
study-specific procedures (i.e. all of the procedures described in the protocol). The process of 
obtaining informed consent should be documented in the patient source documents.  
Novartis will provide to investigators in a separate document a proposed informed consent form 
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. 
10.3 
Responsibilities of the investigator and IRB/IEC 
The protocol and the proposed informed consent form must be reviewed and approved by a 
properly constituted Institutional Review Board/Independent Ethics Committee/Research 
Ethics Board (IRB/IEC) before study start. A signed and dated statement that the protocol and 
informed consent have been approved by the IRB/IEC must be given to Novartis before study 
initiation. Prior to study start, the investigator is required to sign a protocol signature page 
confirming his/her agreement to conduct the study in accordance with these documents and all 
of the instructions and procedures found in this protocol and to give access to all relevant data 
and records to Novartis monitors, auditors, Novartis Clinical Quality Assurance representatives, 
designated agents of Novartis, IRBs/IECs, and regulatory authorities as required. If an 
inspection of the clinical site 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 trial will be either submitted for publication 
and/or posted in a publicly accessible database of clinical trial results. 
11 
Protocol adherence 
Investigators ascertain they will apply due diligence to avoid protocol deviations. Under no 
circumstances should the investigator contact Novartis or its agents, if any, monitoring the trial 
to request approval of a protocol deviation, as requests to approve deviations will not be granted. 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants.  Under no circumstances should an investigator collect additional data or 


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conduct any additional procedures for any research related purpose involving any 
investigational drugs.  
If the 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 site should be informed within 10 
working days or less, if required by local regulations. 
12 
References 
References are available upon request 
Chobanian AV, Bakris GL, Black HR (2003) Seventh report of the joint national committee 
on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension; 
42:1206–1252. 
Committee for medicinal products for human use (CHMP), European Medicines Agency for 
the Evaluation of Medicines for Human Use (2001) Guideline for choice of control group in 
clinical Trials.   CPMP/ICH/364/96 corr document. London, UK. 
Committee for medicinal products for human use (CHMP), European Medicines Agency for 
the Evaluation of Medicines for Human Use (2004) Guideline on clinical investigation of 
medicinal products indicated for the treatment of psoriasis. CHMP/EWP/2454/02 corr 
document. London, UK.  
Fredriksson T and Pettersson U (1978) Severe psoriasis-oral therapy with a new retinoid. 
Dermatologica; 157:238-44. 
Finlay AY, Khan GK (1994) Dermatology Life Quality Index (DLQI): A simple practical 
measure for routine clinical use. Clin Exp Dermatol; 19:210–216. 
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, 
multicentre, randomized dose-finding trial. Br J Dermatol; 152:1219-27. 
Lohman TG, Roche AF, (1988) Anthropometric standardization reference manual. Martoral 
R(eds) Champaign, IL: Human Kinetics. 
Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, et al. (2007) Guidelines for the 
Management of Arterial Hypertension: The Task Force for the Management of Arterial 


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Hypertension of the European Society of Hypertension (ESH) and of the European Society of 
Cardiology (ESC). J Hypertens; 25:1105–1187. 
Newcombe RG (1998) Two-sided confidence intervals for the single proportion: comparison 
of seven methods. Statistics in Medicine; 17: 857-872.  
Weisman S, Pollack CR, Gottschalk RW (2003) Psoriasis disease severity measures: 
comparing efficacy of treatments for severe psoriasis. J Dermatolog Treat; 14:158-165. 
WHO regional office for Europe, Nutrition Unit. (1988) Classification and description of 
anthropometric data. EUR/ICP/NUT/125 document. Copenhagen, Denmark. 


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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 
Whether action needs to be taken to address notable laboratory or vital signs values will be 
decided by the investigator, taking into account the overall status of the subject. No specification 
is foreseen as part of the study protocol. 
 
Liver Function and Related Variables 
Alanine transaminase (ALT) (SGPT):  
> 3 x Upper Limit of Normal (ULN) 
Aspartate transaminase (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/dL decrease from baseline 
Platelet count:  
 
 
 
< Lower Limit of Normal (LLN) 
White blood cell count:  
 
 
< 0.8 x LLN 
Neutrophils:   
 
 
 
< 0.9 x LLN 
Eosinophils:   
 
 
 
> 1.1 x ULN 
Lymphocytes:  
 
 
 
> 1.1 x ULN 
Urinalysis Variable 
Protein urine dipstick:  
 
 
++* 
 
* ++ is ≥ 100 mg/dL 


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14 
Appendix 2: Liver event definitions and follow-up 
requirements 
Table 14-1 
Liver Event Definitions 
 
Definition/ threshold 
Adverse event of special 
interest 
 
Laboratory values 
ALT or AST > 3 x ULN 
 
ALP > 2 x ULN 
 
TBL > 1.5 x ULN 
Medically significant 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 
 
 
 


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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 γGT 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 γGT 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 γGT 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 γGT until 
resolutionc (frequency at 
investigator discretion) 
> 3 to ≤ 5 x ULN  
(patient is 
asymptomatic) 
AESI 
Central laboratory to report to 
Investigator & 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 & Novartis 
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 
Repeat LFT once or twice in the 
weekIf elevation persists, 
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 γGT until 
resolutionc (frequency at 
investigator discretion) 
Test for hemolysis (e.g., 
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 
weekIf 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 γGT 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 three subsequent monitoring visits at least 2 weeks apart, remain at elevated level after a 
maximum of 6 months, liver transplantation, and death. 
 
 
 
 


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15 
Appendix 3: Blood collection log for pharmacokinetics (PK) and 
immunogenicity (IG) 
Table 15-1 
Blood collection log for PK 
Visit Name 
Time point 
Volume 
(approx
.) 
Analyte 
Sample number 
Dose Reference ID/ 
PK collection 
number** 
Week 521 
Pre-dose 
(2 mL) 
AIN457 for 
PK 
(5) 
(5) 
Week 64 
Pre-dose 
2 mL 
AIN457 for 
PK 
7 
7 
Week 76 
Pre-dose 
2 mL 
AIN457 for 
PK 
8 
8 
Week 104 
Pre-dose 
2 mL 
AIN457 for 
PK 
9 
9 
Week 116 
Pre-dose 
2 mL 
AIN457 for 
PK 
10 
10 
Week 128 
Pre-dose 
2 mL 
AIN457 for 
PK 
11 
11 
Week 156 
Pre-dose 
2 mL 
AIN457 for 
PK 
12 
12 
Week 208 
Pre-dose 
2 mL 
AIN457 for 
PK 
13 
13 
Week 260 
672 hours* 
2 mL 
AIN457 for 
PK 
14 
14 
Week 268 
(F8) 
2016 
hours* 
2 mL 
AIN457 for 
PK 
15 
14 
1The data and sample numbering for Week 52 visit (enrollment) will have been collected as part of the 
end of maintenance visit (Week 52) from core study CAIN457A2304 or CAIN457A2307 
* Scheduled post-dose time points for sample numbers 14 and 15 (672 hours and 2016 hours post-
dose, respectively) refer to the last dose given at Week 256 as time 0. 
** If a PK sample is collected at an unscheduled visit, the sample numbers will follow the pattern, 
1001, 1002, etc. 


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Table 15-2 
Blood collection log for IG 
Visit Name 
Time point 
Volume 
(approx.) 
Analyte 
PK collection number** 
Week 521 
Pre-dose 
(2 mL) 
anti-AIN457 for 
IG 
(504) 
Week 76 
Pre-dose 
2 mL 
anti-AIN457 for 
IG 
506 
Week 104 
Pre-dose 
2 mL 
anti-AIN457 for 
IG 
507 
Week 128 
Pre-dose 
2 mL 
anti-AIN457 for 
IG 
508 
Week 156 
Pre-dose 
2 mL 
anti-AIN457 for 
IG 
509 
Week 208 
Pre-dose 
2 mL 
anti-AIN457 for 
IG 
510 
Week 260 
672 hours* 
2 mL 
anti-AIN457 for 
IG 
511 
Week 268(F8) 
2016 
hours* 
2 mL 
anti-AIN457 for 
IG 
512 
1The data and sample numbering for Week 52 visit (enrollment) will have been collected as part of the 
end of maintenance visit (Week 52) from core study CAIN457A2304 or CAIN457A2307 
* Scheduled post-dose time points for sample numbers 511 and 512 (672 hours and 2016 hours post-
dose, respectively) refer to the last dose given at Week 256 as time 0. 
** If an IG sample is collected at an unscheduled visit, the sample numbers will follow the pattern, 
3001, 3002, etc. 


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16 
Appendix 4: Pharmacokinetics (PK) and immunogenicity 
(IG) sample labeling information 
16.1.1 
PK sample handling 
The samples must be labeled as in the following example and as provided by the central 
laboratory  
Study code: 
CAIN457A2304E1 
Site: 
cccc  
(4 digits for the current site number) 
Subject: 
 
 
 
Ccccrrr 
(4 digits for the site number where the subject was enrolled concatenated 
with 3 digits for the assigned subject number. Add ‘0’ ahead of the numbers 
if needed to obtain the correct number of total digits) 
Sample number: 
As indicated in Table 15-1 
Analyte: 
AIN457 for PK 
Labels will be provided by the central laboratory with all information preprinted. 
As PK samples are managed by a central laboratory, no added label should cover the original 
label. 
16.1.2 
IG sample handling 
The samples must be labeled as in the following example and as provided by the central 
laboratory  
Study code: 
CAIN457A2304E1 
Site: 
cccc  
(4 digits for the current site number) 
Subject: 
Ccccrrr 
(4 digits for the site number where the subject was enrolled concatenated 
with 3 digits for the assigned subject number. Add ‘0’ ahead of the numbers 
if needed to obtain the correct number of total digits) 
Sample number: 
As indicated in Table 15-2  
Analyte: 
anti-AIN457 for IG 
Labels will be provided by the central laboratory with all information preprinted. 
As IG samples are managed by a central laboratory, no added label should cover the original 
label. 
  

SAP_001.pdf: 
Clinical Development 
Secukinumab (AIN457) 
Clinical Trial Protocol CAIN457A2304E1 / NCT01640951
A multicenter, double-blind and open label, 4 year extension study of 
subcutaneous secukinumab in prefilled syringes, assessing long-term 
safety, tolerability and efficacy in subjects with moderate to severe 
chronic plaque-type psoriasis treated with either a fixed dose regimen or 
on a retreatment at start of relapse regimen 
RAP Module 3– Detailed Statistical Methodology 
Final Analysis 
Author: 
 
Document type: 
RAP Documentation 
Document status: 
Amendment 1.0 
Release date: 
11-Apr-2018
Number of pages: 
49 
Property of Novartis 
Confidential 
May not be used, divulged, published or otherwise disclosed 
without the consent of Novartis 


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Document History – Changes compared to previous version of RAP module 3. 
Version 
Date 
Changes 
1.0 
 
First draft (initial) version 
 
Amendment 
1.0 
11-Apr-18 
To correct formatting for bookmarks. 
 
 
 
 
 


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Table of contents 
Table of contents ................................................................................................................. 3 
List of tables ........................................................................................................................ 4 
List of figures ...................................................................................................................... 5 
List of abbreviations ............................................................................................................ 6 
1 
Statistical methods planned in the protocol and determination of sample size ................... 8 
1.1 
Statistical and analytical plans ................................................................................. 8 
1.1.1 
Changes to statistical methods planned in the protocol .......................... 9 
1.1.2 
Footnotes ................................................................................................. 9 
1.2 
Subjects and treatments ......................................................................................... 10 
1.3 
Subgroup definitions .............................................................................................. 15 
1.4 
Assessment windows, baseline and post baseline definitions, missing data 
handling ................................................................................................................. 15 
1.4.1 
Assessment windows ............................................................................ 15 
1.4.2 
Study Day 1 and other study days ......................................................... 15 
1.4.3 
Screening (core and extension), baseline and post-baseline 
definitions .............................................................................................. 15 
1.4.4 
Visits windows ...................................................................................... 16 
1.4.5 
Multiple assessments within visit windows .......................................... 19 
1.4.6 
Day of last dose of study treatment ....................................................... 20 
1.5 
Subject disposition, background and demographic characteristics ....................... 21 
1.5.1 
Subject disposition ................................................................................ 21 
1.5.2 
Background and demographic characteristics ....................................... 21 
1.5.3 
Medical history ...................................................................................... 22 
1.6 
Study medication ................................................................................................... 22 
1.7 
Concomitant medication ........................................................................................ 23 
1.8 
Efficacy evaluation ................................................................................................ 23 
1.8.1 
Variables ............................................................................................... 23 
1.8.1.1 
Definition of PASI and related variables .............................................. 25 
1.8.1.2 
Health Assessment Questionnaire - Disability Index (HAQ-DI) .......... 27 
1.8.1.3 
Overview of analysis methods of efficacy variables ............................. 29 
1.8.2 
Statistical hypothesis, model, and method of analysis .......................... 30 
1.8.3 
Testing strategy ..................................................................................... 30 
1.8.4 
Handling of missing values/censoring/discontinuations ....................... 30 
1.8.4.1 
Multiple imputations for response ........................................................ 30 
1.8.5 
Supportive analyses ............................................................................... 30 
1.8.6 
Secondary variables .............................................................................. 30 


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1.8.7 
Methods of analysis............................................................................... 30 
1.8.8 
Exploratory analyses ............................................................................. 31 
1.8.9 
Biomarkers ............................................................................................ 32 
1.8.10 
Health-related Quality of Life (HRQoL) .............................................. 32 
1.9 
Standard safety evaluation ..................................................................................... 33 
1.9.1 
Adverse events ...................................................................................... 33 
1.9.2 
Laboratory data ..................................................................................... 35 
1.9.3 
Vital signs.............................................................................................. 38 
1.9.4 
Electrocardiogram (ECG) ..................................................................... 39 
1.9.5 
Immunogenicity .................................................................................... 39 
1.10 
Sample size calculation .......................................................................................... 40 
1.11 
Power for analysis of key secondary variables ...................................................... 40 
1.12 
Interim analyses ..................................................................................................... 40 
2 
Clinical Study Report -  Appendix 16.1.9 Documentation of statistical methods ............ 41 
2.1 
Analysis of continuous data ................................................................................... 41 
2.2 
Analysis of binary (and categorical) data .............................................................. 41 
2.2.1 
Summary statistics for binary and categorical data ............................... 41 
2.2.2 
Multiple imputations for response variables ......................................... 41 
2.3 
Crude incidence and related risk estimates ............................................................ 43 
2.3.1 
Crude incidence and 100*(1-α)% confidence interval .......................... 43 
2.4 
Exposure adjusted incidence rate and related risk estimates ................................. 44 
2.4.1 
Exposure adjusted incidence rate and 100*(1-α)% confidence 
interval ................................................................................................... 44 
2.5 
Subject reported outcomes ..................................................................................... 44 
2.5.1 
Dermatology Life Quality Index (DLQI) .............................................. 44 
2.5.2 
EQ-5D ................................................................................................... 46 
3 
References ......................................................................................................................... 48 
 
List of tables 
Table 1-1 
Subject classification rules .................................................................... 10 
Table 1-2 
Analysis by treatment group ................................................................. 13 
Table 1-8 
Assessment windows for scheduled visits ............................................ 17 
Table 1-9 
Rules for selecting values for analysis .................................................. 20 
Table 1-10 
Primary, secondary and exploratory variables ...................................... 24 
Table 1-11 
The PASI scoring system ...................................................................... 26 
Table 1-12 
The IGA mod 2011 rating scale ............................................................ 27 


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Table 1-13 
Companion aids/devices items for HAQ-DI categories ........................ 29 
Table 1-14 
Overview of analysis methods for efficacy variables ........................... 29 
Table 1-18 
CTCAE grades for laboratory parameters to be analyzed .................... 36 
Table 1-19 
Liver-related events ............................................................................... 38 
Table 1-20 
Criteria for notable vital sign abnormalities .......................................... 39 
Table 2-2 
Companion aids/devices items for HAQ-DI categories ........................ 47 
 
List of figures 
No table of contents entries found. 


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List of abbreviations 
 
AE 
adverse event 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body Mass Index 
BSA 
body surface area 
CHMP  
Committee for medicinal products for human use  
CSR 
clinical study report 
CTCAE  
Common Terminology Criteria for Adverse Events 
DHP  
Data Handling Plan 
DLQI 
Dermatology Life Quality Index 
eCRF 
electronic case report/record form 
FAS 
Full analysis set 
FDA 
United States Food and Drug Administration 
HAQ 
Health Assessment Questionnaire© 
HAQ-DI 
Health Assessment Questionnaire© – Disability Index 
ICH 
International Conference on Harmonisation of Technical Requirements 
for Registration of Pharmaceuticals for Human Use 
IGA 
investigator’s global assessment 
IGA mod 2011 
Novartis Investigator’s Global Assessment modified 2011 
IRT 
interactive response technology 
i.v. 
intravenous(ly) 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
NMQ 
Novartis MedDRA Query 
PASI 
Psoriasis Area and Severity Index 
PD 
protocol deviation 
PDS 
Programming Datasets Specifications 
PsA 
psoriatic arthritis 
PT 
Preferred Term 
RAP 
Report and Analysis Plan 
RMP 
Risk Management Plan 


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SAE 
serious adverse event 
SoR 
Start of relapse 
s.c. 
subcutaneous(ly) 
SOC 
System Organ Class 
 
 
 


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1 
Statistical methods planned in the protocol and 
determination of sample size 
Data will be analyzed by Novartis using SAS according to the data analysis section 9 of the 
study protocol which is available in Appendix 16.1.1 of the CSR.  Important information is 
given in the following sections and details are provided, as applicable, in Appendix 16.1.9 of 
the CSR. 
1.1 
Statistical and analytical plans 
The planned analysis is described in Section 9 (Data Analysis) of the study protocol which is 
available in Appendix 16.1.1 of the CSR.   
This document covers the statistical and analytical plans for the final analysis. All data collected 
up to end of the study will be analyzed as part of final analysis. 
The primary objective of the study is to assess long-term safety and tolerability of secukinumab 
in subjects with moderate to severe chronic plaque-type psoriasis who completed treatment in 
the core studies CAIN457A2304 and CAIN457A2307. 
The secondary objectives are: 
• To evaluate the long-term efficacy of 150 mg and 300 mg of secukinumab administered 
at the start of relapse versus fixed interval regimens of 150 mg and 300 mg of 
secukinumab respectively, in subjects with moderate to severe chronic plaque-type 
psoriasis who are PASI 75 responders at Week 12, with respect to PASI 75 response: 
o at Weeks 104 and 156, for subjects in the fixed interval regimens, or 
o at Weeks 92 and 144, for subjects in the retreatment at start of relapse regimen 
who do not require active treatment at Week 92 or 144, respectively, or 
o at Weeks 104 and 156, for subjects in the retreatment at start of relapse regimen 
who do require active treatment at Week 92 or 144, respectively. 
• To evaluate the efficacy of secukinumab treatment regimens in subjects with moderate 
to severe chronic plaque-type psoriasis with respect to PASI 50/75/90/100 and IGA mod 
2011 0 or 1 response over time. 
• To evaluate the effects of treatment regimens with secukinumab in subjects with 
moderate to severe chronic plaque type psoriasis with respect to PASI score and IGA 
mod 2011 score over time 
• To assess the effects of secukinumab treatment regimens with respect to EQ-5D score 
over time 
• To investigate the effects of treatment regimens with secukinumab in subjects with 
moderate to severe chronic plaque-type psoriasis with respect to changes in DLQI over 
time 
• To investigate the effects of treatment regimens with secukinumab in subjects with 
moderate to severe chronic plaque-type psoriasis with respect to DLQI 0 or 1 
achievement over time 
• To investigate the potential development of immunogenicity against secukinumab 


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• To investigate the occurrence of relapses (achieved maximal PASI improvement from 
baseline in core study is reduced by >50%) and rebounds in subjects on secukinumab 
therapy 
The exploratory objectives are: 
• 
 
• To explore the effects of secukinumab with respect to the HAQ-DI in subjects from core 
study CAIN457A2304 with psoriatic arthritis (PsA) at baseline over time 
Summary statistics for continuous variables will include N, mean, standard deviation, minimum, 
lower quartile, median, upper quartile, maximum. Summary statistics for discrete variables will 
be presented in contingency tables and will include absolute and relative frequencies. 
1.1.1 
Changes to statistical methods planned in the protocol 
Table 1-11 is a modified version of table 6-3 of the protocol to clearly indicate that the area 
score is derived from area% without rounding.  
For the maintenance of response analysis, the non-responder imputation method defined in the 
protocol will be dropped. The as observed result for PASI and IGA responses will be 
primarily looked into; the multiple imputation method will be provided as well. Assessment 
during follow-up period excluded. 
In addition to the planned analysis on adverse events, by 1-year interval analysis on the 
adverse events will be provided in order to assess the occurence of adverse events over time. 
1.1.2 
Footnotes 
Footnotes on outputs will be kept to a minimum also for outputs not covered in [Efficacy MAP 
M7.1] or [Safety MAP M7.1].  
Footnotes will generally be provided for 
• abbreviations used in the output; abbreviations used on several outputs, e.g. for listings in 
Appendix 16.2 can be presented on a separate page and do not have to be repeated as 
footnotes on each listing 
• sorting order of categories, e.g. for sorting within MedDRA (Medical Dictionary for 
Regulatory Activities) hierarchy levels 
• MedDRA version used for reporting of MedDRA coded data 
Footnotes will generally NOT be given for 
• units displayed on the output 
• interpretation of results (e.g. “odds ratio larger 1 favors active treatment”) 
• information that can be retrieved from the statistical section of the clinical study report (CSR) 
unless it is not identifiable from the output, e.g. 
• explanation of analysis model used unless results of more than one model are displayed 
on an output 
• derivations of variables (e.g. BMI will not be explained on a footnote) 
• information that will be provided in the clinical study protocol and/or methods section of 
the CSR (e.g. baseline definition if this is specified in the statistical section of the CSR) 


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1.2 
Subjects and treatments  
 
The following analysis sets will be used for the data analysis. 
Extension Full analysis set (FAS): The FAS will be comprised of all subjects from the 
randomized set to whom study treatments has been assigned and entered the extension study. 
Following the intent-to-treat principle, subjects will be analyzed according to the treatment 
assigned to at randomization in A2304 and A2307 and thereafter reassigned to treatment at 
Week 156. If the actual stratum is different to the assigned stratum in IRT, the actual stratum 
will be used in analyses. 
Of note, subjects excluded from the randomized set will be excluded from the FAS. 
Extension Safety set: The safety set includes all subjects who took at least one dose of study 
treatment during the extension treatment period. Subjects will be analyzed according to 
treatment received. The treatment received will be set to the treatment randomized. But if a 
subject has received the wrong treatment during the entire study, the treatment received will be 
set to this wrong treatment.  
Table 1-1 
Subject classification rules 
Analysis set 
PD Population Codes that 
cause subject to be excluded 
Non-PD criteria that cause a 
subject to be excluded 
FAS (Full Analysis Set)  
GCP01, GCP06, INCL01, 
INCL16, INCL18 
 No post baseline efficacy 
assessment 
Safety 
GCP01, GCP06, INCL01, 
INCL16, INCL18 
 Not treated in the extension 
Note: Protocol Deviation (PD) Populations Codes are available from the study DHP (Data 
Handling Plan). 
Core study A2304: Randomization was stratified by geographical region and by body weight 
collected at Visit 2 (< 90 kg or ≥90 kg).  In study sites selected for psoriatic arthritis assessments 
according to ACR criteria, randomization was also stratified according to history of psoriatic 
arthritis at screening. 
Subjects were randomized using a 1:1 ratio into one of the treatment groups below: 
• Secukinumab 150 mg group: AIN457 150 mg s.c. q week x 5 followed by 150 mg s.c. q 
4 weeks  
• Secukinumab 300 mg group: AIN457 300 mg s.c. q week x 5 followed by 300 mg s.c. q 
4 weeks  
 
At Week 12 in core study A2304, subjects were classified into 3 categories: 
PASI non-responders:  
were discontinued from study  
PASI partial responders:  were offered participation into trial CAIN457A2307.  
PASI 75 responders:  
within each dose group (150 or 300 mg s.c.) were re-
randomized to one of the two maintenance treatment arms in a ratio of 1:1 (either “fixed 
interval” or “retreatment at start of relapse”) from Week 12 to Week 48.   


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Thus re-randomization will result to four treatment arms overall in A2304 and also one 
treatment arm in A2307: 
Fixed-time interval regimen – “FI” either 150 or 300 mg s.c. secukinumab:  In the 
maintenance period subjects will receive the same dose they received during the induction 
period. Thus, secukinumab 150 mg subjects will continue to receive 150 mg secukinumab every 
four weeks, and secukinumab 300 mg subjects will continue to receive 300 mg secukinumab 
every four weeks, from week 12 up to and including week 48. 
Retreatment at start of relapse regimen – “SOR”: “start of relapse” either 150 or 300 mg 
s.c. secukinumab: “Start of relapse” will be defined as a loss of ≥20% of the maximum PASI 
gain achieved during the study compared to baseline, and a loss of PASI 75 response.  
Whenever a subject fulfills the start of relapse criteria, active secukinumab will be administered 
at their scheduled visits (i.e. every four weeks) until the subject is back to PASI 75 response. 
The dose administered in the maintenance period (secukinumab 150 mg  or 300 mg) will be 
identical to the dose that these subjects received during the induction period. If a subject does 
not fulfill the criteria of a start of relapse or is back to PASI 75 response after a start of relapse, 
they will receive placebo injections (two injections per dose) to maintain the blind. This 
treatment regimen is applied every four weeks, from week 12 up to and including week 48. 
Open label (OL) 300 mg s.c. secukinumab: All the partial responders at week 12 in induction 
period in A2304 will enter A2307 double blind i.v. period (for 8 weeks) and these subjects will 
be randomized with 1:1 ratio into either “300 mg s.c. secukinumab” or “10 mg per kg i.v. 
secukinumab”.  All the subjects will enter open label 300 mg s.c. secukinumab maintenance 
period from week 8 to week 40.  
All the subjects who are eligible from the above 5 treatment groups (4 treatment groups from 
A2304 and 1 treatment group from A2307) enter the A2304E1 extension study treatment period 
and continue with same treatment groups. At Week 156, patients under AIN457 150mg FI arm, 
AIN457 150mg SOR arm, and AIN457 300mg SOR arm could be switched to AIN457 300mg 
FI arm as determined by physician’s judgement. 
 
For the final analysis, data will be presented for the following treatment groups: 
• AIN457 150 mg FI  
• AIN457 150 mg FI switch to AIN457 300mg FI 
• AIN457 150 mg FI combined non-switch and switch 
• AIN457 300 mg FI  
• AIN457 150 mg SoR non-switched 
• AIN457 150mg SoR switch to AIN457 300mg FI 
• AIN457 300 mg SoR non-switched 
• AIN457 300mg SoR switch to AIN457 300mg FI 
• AIN457 300 mg OL 
• Any AIN457 300mg 
• Any AIN457 150mg 
• Any AIN457 


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Note: any AIN457 300mg (including AIN457 150mg FI switch to AIN457 300mg FI, AIN457 
300mg FI, AIN457 150mg SoR switch to AIN457 300mg FI, AIN457 300mg SoR, AIN457 
300mg SoR switch to AIN457 300mg FI and AIN457 300mg OL); any AIN 150mg(including 
AIN457 150mg FI and AIN457 150mg SoR); Any AIN457 including all the groups above. 
The following study periods will be considered for analysis: 
• Extension study period: Week 52 post-dose to Week 268; 
• Entire study period: Combination of Induction (in A2304 core) period + Maintenance 
(in A2304 and in A2307) period + Core follow-up period (consider only for subjects 
who enter E1 after core follow-up period)+ Treatment period in E1 [Initial 
Randomization in A2304 core to week  268] (including follow-up period); 
• Entire treatment period: Combination of Induction (in A2304 core) period + 
Maintenance (in A2304 and in A2307) period + Core follow-up period (consider only 
for subjects who enter E1 after core follow-up period) + Treatment period in E1 [Initial 
Randomization in A2304 core to week  260]  
• Follow-up 2 period: after W268 visit to end of the study. 
 
 


 
 
 
 
 
Table 1-2 
Analysis by treatment group 
Endpoint/analysis 
AIN457  150 mg FI 
AIN457 150 mg FI switch to 300mg FI 
AIN457 300 mg FI 
AIN457 150 mg SoR 
AIN457 150 mg SoR switch 300 mg FI 
AIN457 300 mg SoR 
AIN457 300 mg SoR switch 300 mg FI 
AIN457 300mg OL  
AIN457 150mg 
FI(NSW+SW) 
Any AIN457 150mg 
Any AIN457 300mg 
Any AIN457 
Subject disposition  
X 
 
 
X 
Demography & baseline characteristics 
X 
 
 
X 
Previous & concomitant medication 
X 
 
 
X 
Medical history 
X 
 
 
X 
Study medication: duration of exposure 
X 
 
X 
X 
Maintanance of PASI 75 response 
X 
 
 
 
PASI 50/75/90/100 and IGA mod 2011 0 or 1 
response over time  
X 
X 
 
 
PASI score over time 
X 
X 
 
 
IGA mod 2011 score over time 
X 
X 
 
 
Relapse 
X 
 
 
 
Rebound 
X 
 
 
 
DLQI 0 or 1 achievement 
X 
X 
 
 


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Endpoint/analysis 
AIN457  150 mg FI 
AIN457 150 mg FI switch to 300mg FI 
AIN457 300 mg FI 
AIN457 150 mg SoR 
AIN457 150 mg SoR switch 300 mg FI 
AIN457 300 mg SoR 
AIN457 300 mg SoR switch 300 mg FI 
AIN457 300mg OL  
AIN457 150mg 
FI(NSW+SW) 
Any AIN457 150mg 
Any AIN457 300mg 
Any AIN457 
DLQI 
X 
 
 
 
EQ-5D 
X 
 
 
 
HAQ©-DI 
X 
X 
 
 
Safety analysis 
X 
 
X 
X 
 


 
 
 
 
 
1.3 
Subgroup definitions 
No subgroup analysis will be presented in the final analysis. HAQ-DI will be analyzed only for 
subjects with PsA at Core study entry 
1.4 
Assessment windows, baseline and post baseline definitions, 
missing data handling 
1.4.1 
Assessment windows 
No assessment windows have been defined for this study. Visit windows are described below. 
If not otherwise specified, ‘first dose’, ‘randomization’ and ‘baseline’ are with respect to core 
study. 
1.4.2 
Study Day 1 and other study days 
The first day of administration of randomized study treatment (first dose) is defined as Study 
Day 1 or Day 1.  
All other study days will be labeled relative to Day 1.  For event dates on or after Day 1, study 
day for a particular event date is calculated as [Date of event] – [Date of first dose]+1, i.e., Day 
2, Day 3, etc., will be one day, two days, etc., after Day 1, respectively. For the dates before 
Day 1, study day for an event date is calculated as [Date of event] – [Date of first dose], i.e., 
Day -1, Day -2, etc., will be one day, two days, etc., before Day 1, respectively. Duration of an 
event will be calculated as (Event end date – Event start date + 1). 
The descriptor “Day 0” will not be used. 
Missing data  
For laboratory test values below Lower Level of Quantification (LLQ) or above Upper Level 
of Quantification (ULQ) will be imputed as LLQ or ULQ value, respectively. The numerical 
part of the reported result will be treated as the actual LLQ or ULQ. These laboratory values 
will be displayed in listings using the standard unit with the reported sign (“<” or “>”).” 
1.4.3 
Screening (core and extension), baseline and post-baseline definitions 
Screening refers to any procedures (e.g., checking inclusion and exclusion criteria) performed 
prior to the date of first dose of study treatment in core study A2304 (for safety analysis) or 
prior to the first randomization date (for efficacy analysis) in A2304. Of note, re-randomization 
will not be used for baseline definition and only one baseline value will be defined referring to 
the first randomization. 
Screening2 refers to any procedures (e.g., checking inclusion and exclusion criteria) performed 
prior to the date of first dose of study treatment in extension study A2304E1 (for safety analysis 
and efficacy analysis). 


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Per protocol, subject informed consent must be obtained prior to performing any study related 
activity.  The date of signing informed consent is the start date of screening period.  Any 
assessment obtained during the screening period will be labeled screening assessment.  
Assessments made on Day 1 may occur before or after the randomization or the first dose. 
Further information will be found in [PDS]. 
For efficacy analyses, baseline is the last assessment (including unscheduled visits) obtained 
before the first randomization in the core study A2304. All assessments obtained after 
randomization are considered as post-baseline unless otherwise specified. 
For safety analyses, baseline is the last assessment (including unscheduled visits) obtained 
before the first dose of study treatment. All assessments obtained after the first dose of study 
drug are considered as post-baseline unless otherwise specified. 
In general, a baseline value refers to the last measurement made prior to administration of the 
first dose of study treatment. However, for PROs (e.g. patient’s assessment of PsA pain), lab, 
ECG if no pre-treatment value exists, also a value recorded after first dose can be used as 
baseline if it was collected on the same day as first dose. 
1.4.4 
Visits windows 
Visit- windows will be used for the data that is summarized by analysis visit; they are based on 
the study evaluation schedule and comprise a set of days around the nominal visit day. For any 
assessment, there are the protocol defined scheduled visits around which visit windows were 
created to cover the complete range of days within the study.  The visit windows are shown in 
Table 1-8 
. In this table, the days are counted since the first dose of study treatment (study days) for safety 
assessments, and the days are counted since the date of randomization for efficacy assessments. 
These visit windows apply to measurements taken at every visit. For assessments collected less 
often different visit windows will be applied as detailed below. 
When visit windows are used, all visits will be re-aligned, i.e., they will be mapped into one of 
the visit windows. E.g., if the Week 4 visit of a subject is delayed and occurs on Day 46 instead 
of on Day 29, say, it will be re-aligned to visit window Week 8. In the case of major deviations 
from the visit schedule, or due to unscheduled visits, several assessments of a subject may fall 
in a particular visit window (either scheduled or unscheduled). Statistical approaches to handle 
multiple assessments in a given visit window are specified below. 
Of note, subjects are allowed to have gaps in visits. 
 
 


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Table 1-8 
Assessment windows for scheduled visits 
Analysis Visit 
Week 
(relative to 
baseline of 
core) 
Scheduled Day 
Visit Window 
Baseline 
BSL 
1 
-28 days to Day 1* 
Week 1 
1 
8 
Day 2-11 
Week 2 
2 
15 
Day 12-18 
Week 3 
3 
22 
Day 19-25 
Week 4 
4 
29 
Day 26-43 
Week 8 
8 
57 
Day 44-71 
Week 12 
12 
85 
Day 72-99 
Week 16 
16 
113 
Day 100-127 
Week 20 
20 
141 
Day 128-155 
Week 24 
24 
169 
Day 156-183 
Week 28 
28 
197 
Day 184-211 
Week 32 
32 
225 
Day 212-239 
Week 36 
36 
253 
Day 240-267 
Week 40 
40 
281 
Day 268-295 
Week 44 
44 
309 
Day 296-323 
Week 48 
48 
337 
Day 324-351 
Ext1 Week 52 / Screening 2 
52 
365 
Day 352-379 
Week 56 
56 
393 
Day 380-407 
Week 60 
60 
421 
Day 408-435 
Week 64 
64 
449 
Day 436-463 
Week 68 
68 
477 
Day 464-491 
Week 72 
72 
505 
Day 492-519 
Week 76 
76 
533 
Day 520-547 
Week 80 
80 
561 
Day 548-575 
Week 84 
84 
589 
Day 576-603 
Week 88 
88 
617 
Day 604-631 
Week 92 
92 
645 
Day 632-659 
Week 96 
96 
673 
Day 660-687 
Week 100 
100 
701 
Day 688-715 
Week 104 
104 
729 
Day 716-743 
Week 108 
108 
757 
Day 744-771 
Week 112 
112 
785 
Day 772-799 


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Week 116 
116 
813 
Day 800-827 
Week 120 
120 
841 
Day 828-855 
Week 124 
124 
869 
Day 856-883 
Week 128 
128 
897 
Day 884-911 
Week 132 
132 
925 
Day 912-939 
Week 136 
136 
953 
Day 940-967 
Week 140 
140 
981 
Day 968-995 
Week 144 
144 
1009 
Day 996-1023 
Week 148 
148 
1037 
Day 1024-1051 
Week 152 
152 
1065 
Day 1052-1079 
Week 156 
156 
1093 
Day 1080-1107 
For AIN457 300mg FI/AIN457 300mg SoR switch to AIN457 300mg FI/AIN457 
150mg FI/AIN457 150mg FI switch to AIN457 300mg FI/AIN457150mg SoR 
switch to AIN457 300mg FI 
Week 168 
168 
1177 
Day 1108-1219 
Week 180 
180 
1261 
Day 1220-1303 
Week 192 
192 
1345 
Day 1304-1401 
Week 208 
208 
1457 
Day 1402-1499 
Week 220 
220 
1541 
Day 1500-1583 
Week 232 
232 
1625 
Day 1584-1667 
Week 244 
244 
1709 
Day 1668-1765 
Week 260 
260 
1821 
Day 1766-1835 
Week 264 
264 
1849 
Day 1836 – 1863 
Week 268 
268 
1877 
Day 1864 - 1891 
For AIN457 300mg SoR/AIN457 150mg SoR 
Week 160 
160 
1121 
Day 1108-1135 
Week 164 
164 
1149 
Day 1136-1163 
Week 168 
168 
1177 
Day 1164-1191 
Week 172 
172 
1205 
Day 1192-1219 
Week 176 
176 
1233 
Day 1220-1247 
Week 180 
180 
1261 
Day 1248-1275 
Week 184 
184 
1289 
Day 1276-1303 
Week 188 
188 
1317 
Day 1304-1331 
Week 192 
192 
1345 
Day 1332-1359 
Week 196 
196 
1373 
Day 1360-1387 
Week 200 
200 
1401 
Day 1388-1415 
Week 204 
204 
1429 
Day 1416-1443 
Week 208 
208 
1457 
Day 1444-1471 
Week 212 
212 
1485 
Day 1472-1499 


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* Baseline measurement before the first drug administration for safety assessments and before 
the first randomization in CAIN457A2304 for efficacy assessments. The days are counted since 
the first dose of study treatment for safety assessments, and the days are counted since the date 
of randomization for efficacy assessments. 
For parameters which are not collected at every visit (e.g. weight, DLQI, EQ-5D, HAQ-DI), 
visit windows defined in the tables above will be combined. E.g., if a parameter is measured at 
Week 12 and Week 24 only, Week 12 visit window will extend from Day 2 to Day 99 
(combining Week 1 to Week 12 visit windows), Week 24 will extend from Day 100 to Day 183 
(combining Week 13 to Week 24). If more than one assessment falls into the interval, the rules 
defined in Section 1.4.5 below are applied. 
Maintenance period visits will not be mapped into induction period, and induction period visits 
will not be mapped into maintenance period. For example, if a subject is coming late for the 
Week 12 visit (induction period), and the visit would be fall into the Week 13 (maintenance 
period) visit window, it would not be mapped for the analysis. 
1.4.5 
Multiple assessments within visit windows 
When there are multiple assessments in a particular visit window, the following rules are applied 
to select one value “representing” the subject in summary statistics in a visit window (See Table 
1-8 & Table 1-9). 
For baseline assessment definition see Section 1.4.3. For post-baseline visit windows the 
following applies (unless otherwise specified): 
• for quantitative variables, the closest to the actual visit is chosen (if two assessments have 
the same distance, then the earlier one will be chosen);  
• for qualitative variables, the worst record is selected. It is noted that in the analyses 
performed, worst case is always well defined (e.g., for urine protein values “+” and “++”, 
the worst case is defined as “++”), 
Week 216 
216 
1513 
Day 1500-1527 
Week 220 
220 
1541 
Day 1528-1555 
Week 224 
224 
1569 
Day 1556-1583 
Week 228 
228 
1597 
Day 1584-1611 
Week 232 
232 
1625 
Day 1612-1639 
Week 236 
236 
1653 
Day 1640-1667 
Week 240 
240 
1681 
Day 1668-1695 
Week 244 
244 
1709 
Day 1696-1723 
Week 248 
248 
1737 
Day 1724-1751 
Week 252 
252 
1765 
Day 1752-1779 
Week 256 
256 
1793 
Day 1780-1807 
Week 260 
260 
1821 
Day 1808-1835 
Week 264 
264 
1849 
Day 1836 – 1863 
Week 268 
268 
1877 
Day 1864 - 1891 


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• in case qualitative variables are based on quantitative variables, e.g. PASI 75 response, the 
visit will be assigned to the quantitative variable, and this visit will be used for the derived 
qualitative variable.  
 
Table 1-9 
Rules for selecting values for analysis 
Timing of 
measurement 
Type of data 
Rule 
Baseline 
All data 
See Section 1.4.3 
Post-baseline efficacy 
All data except  DLQI, EQ-5D and 
health assessment 
The measurement closest to the target 
day will be used.  In the event two 
measurements are taken equally apart 
(e.g., 1 day before target date and 1 
day after), the earlier one will be used. 
Post-baseline efficacy 
DLQI, EQ-5D and health 
assessment 
The measurement closest to the target 
day will be used.  In the event two 
measurements are taken equally apart 
the earlier one will be used. 
If two measurements have been taken 
on the same day, select the worst. 
Post-baseline safety 
Summary visit information (e.g. 
lab, ECG, etc.) 
The measurement closest to the target 
day will be used.  In the event two 
measurements are taken equally apart 
(e.g., 1 day before target date and 1 
day after), the earlier one will be used.  
If two measurements are taken on the 
same date/different time then select the 
first one(using the time);  
If two measurements are taken on the 
same date/time/different visit number 
then use the first visit number 
(assuming this is the planned visit);  
If two measurements are taken on the 
same date/time/CRF visit then take the 
average value 
 
Post-baseline safety  
Notable abnormalities (e.g., vital 
signs, ECG), CTCAE grades 
The most extreme measurement in the 
window will be used. Note this means a 
subject can have a notably high and 
notably low measurement within a 
window (analysis period). 
1.4.6 
Day of last dose of study treatment 
The date of last dose will be collected via the CRF.  The subject’s exposure will be calculated 
considering the end of treatment period visit including follow-up 1 period or the last dose date 
+84 days which happened earlier. 
 


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1.5 
Subject disposition, background and demographic 
characteristics 
1.5.1 
Subject disposition 
The number and percentage of subjects in the randomized set who entered and completed study 
periods), and who discontinued the study prematurely (including the reason for discontinuation) 
will be presented for each treatment group. The reason for patients discontinuation from study 
treatment will be presented by yearly interval (analysis visit) for AIN457 150 mg (switch+non-
switch) and AIN457 300 mg. 
1.5.2 
Background and demographic characteristics 
The following common background and demographic variables from core study will be 
analyzed for assessing the baseline comparability: 
Continuous variables: 
o Age (which is derived from date of birth and the screening assessment date) 
o Height  
o Weight  
o Body mass index (BMI)  
Categorical variables: 
o Age categories (<65 years, 65 years and older, 75 years and older) 
o Gender 
o Race 
o Ethnicity 
o Smoking status  
Psoriasis specific baseline characteristics and history of disease will be summarized as well: 
Baseline PASI score ,  baseline PASI (<=20, >20), baseline total BSA baseline IGA mod 2011 
score (at least mild, moderate, severe), Severity of psoriasis, presence of psoriatic arthritis (yes, 
no), types of previous psoriasis therapies, time since diagnosis of psoriasis, time since diagnosis 
of psoriatic arthritis, previous exposure to biologic systemic psoriasis therapy, previous 
exposure to systemic psoriasis therapy, previous exposure to non-biologic systemic psoriasis 
therapy, previous failure to biologic systemic psoriasis therapy, previous failure to systemic 
psoriasis therapy, previous failure to non-biologic systemic psoriasis therapy. 
Previous psoriasis therapy will be combined from previous psoriasis therapy recorded in CORE 
study and also concomitant medications entered in EXTENSION study which started on or 
prior to the inform consent date of CORE study. The ATC code is defined in PDS. 
Body Mass Index (BMI) will be calculated using the following formula: 
BMI = (body weight in kilograms) / (height in meters)2 
For BMI, height and body weight used is the last value prior to randomization. If there is no 
weight recorded prior to taking of study drug, BMI will be missing.  


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Unless otherwise specified, summary statistics will be presented for continuous variables for 
each treatment group and for all subjects (total) in the FAS. The number and percentage of 
subjects in each category will be presented for categorical variables for each treatment group 
and all subjects (total) in the FAS.  
Unless otherwise specified, analyses will be based on the FAS.  
1.5.3 
Medical history 
Any significant prior or active medical condition at the time of signing informed consent will 
be coded using the MedDRA dictionary. These medical conditions will be summarized by 
primary system organ class and preferred term. Psoriasis specific medical history will be 
summarized by treatment group. Previous treatments for psoriasis and whether or not response 
was achieved will be summarized by treatment group. 
The medical history information combines the medical history data collected in CORE study 
and also data entered in AE domain in the extension study which started on or prior to screening 
1.6 
Study medication 
The analysis of study treatment data will be based on the safety set. 
The number of planed and actual injection number will be summarized by yearly interval 
(analysis visit) for entire treatment period and treatment group AIN457 150 mg FI and AIN457 
300 mg FI. 
In case it cannot be identified from the data collected or assumed from the planned treatment 
whether an injection contained placebo or secukinumab, it will be assumed that the syringe 
contained secukinumab. For example this applies to the 150 mg secukinumab treatment group 
(in which subjects should receive both an active and a placebo injection) if only one injection 
is given. If the medication pack number is not available, it will be assumed that the secukinumab 
injection was applied. If this scenario occurs for subjects in the 300 mg treatment group when 
subjects should receive two identical injections, it will be assumed that they received 
secukinumab as planned. 
The duration of exposure to study drug will be summarized by treatment group and yearly 
interval for entire treatment period.  
Duration of exposure will be defined and summarized as follows: 
For extension study period, duration of exposure will be defined as the time from first dose of 
study medication in extension 1 to the end of treatment period in extension 1 study; and for 
entire study period duration of exposure will be defined as the time from first dose of study 
medication in core study to the end of treatment period in extension 1 study. The end of 
treatment period will be defined as the last dose plus 84 days or last visit whichever occurs 
earlier. i.e., for subjects who discontinued or have their last visit earlier than last dose plus 84 
days, the end of study treatment exposure will be the date of the last study visit in the 
corresponding treatment period. 
Duration of exposure (days)=min(End of study visit date, last dose date + 84 days) - first 
dose date + 1 


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Duration of exposure (years) = duration of exposure (days) / 365.25 
Duration of exposure (100-patient years) = duration of exposure (years) / 100 
The analyses of duration of exposure described above will be done for the extension study 
period and for the entire study period. 
1.7 
Concomitant medication 
Medications will be identified using the Novartis Drug and Therapy Dictionary (NovDTD) 
including Anatomical Therapeutic Chemical (ATC) code. Prior and concomitant treatments will 
be summarized by treatment group for the safety set.  
Prior and concomitant medications will be summarized by treatment group in separate tables.  
Medications will be presented in alphabetical order, by ATC codes and grouped by anatomical 
main group (the 1st level of the ATC codes). Tables will also show the overall number and 
percentage of subjects receiving at least one drug of a particular ATC code and at least one drug 
in a particular anatomical main group.  
Prior medications are defined as drugs taken and stopped prior to first dose of study 
treatment.  Any medication given at least once between the day of first dose of randomized 
study treatment, and last dose plus 84 days or last vist (including follow-up visits) whichever 
occurs earlier will be a concomitant medication, including those which were started pre-
baseline and continued into the treatment period.  
In addition, medical procedures and significant non-drug therapies as coded in MedDRA will 
be summarized. 
Prior or concomitant medication will be identified based on recorded or imputed start and end 
dates of medication taken. Further rules will be given in PDS. 
 
Listings of prior or concomitant medication during entire study period and follow-up 2 period 
will be provided separately. 
1.8 
Efficacy evaluation 
1.8.1 
Variables 
The primary objective of the study is to assess long-term safety and tolerability of secukinumab 
in subjects with moderate to severe chronic plaque-type psoriasis who completed treatment in 
the core studies CAIN457A2304 and CAIN457A2307. 
The analysis of the secondary efficacy variables will be based on the FAS. 
The main secondary efficacy analysis is maintenance of response. Maintenance of response is 
defined as follows: 
• for subjects in the fixed interval regimens, maintenance of response is defined as 
PASI 75 response at Weeks 104 and 156  
• for subjects in the start of relapse regimens maintenance of response is defined as  


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• PASI 75 response at Weeks 92 and 144 for subjects who do not require active 
treatment at Week 92 or 144 and 
• PASI 75 response at Weeks 104 and 156 for subjects who do require active treatment 
at Week 92 or 144. 
In order to identify whether active treatment was applied at Weeks 92 and 144 the following 
will be utilized: 
• Visit windows as in Table 1-8 (as for efficacy with date of randomization as day 1) will be 
applied to dosing date. 
• The analysis visit Weeks 92 and 144 will be identified for dosing. The PASI assessment 
for the corresponding CRF visit will be selected.  
• If no dosing for analysis visit Weeks 92 and 144 is identified, it is concluded that no active 
treatment was given. Therefore, the PASI 75 response status of the analysis visit Weeks 
92 and 144 will be considered. 
• For subjects with assigned dosing records at Weeks 92 and 144 but for which no 
corresponding PASI assessment can be assigned, non-responder imputation will be 
performed 
Apply visit windowing to the dosing dates then find the weeks 92 and 144 dosing date.  With 
this dosing date search for the corresponding PASI data with the same date.  If there was no 
AIN dosing at these weeks 92 and 144 then it shall be assumed that the PASI response at Weeks 
92 and 144 will be taken for the maintenance of response parameter. 
 
Table 1-10 lists the variables for the final analysis.  
Table 1-10 
Primary, secondary and exploratory variables 
Variable 
Type 
Long term safety and tolerability of secukinumab 
Primary 
Maintenance of response 
Secondary 
PASI 50/75/90/100 and IGA mod 2011 0 or 1 response over time 
Secondary 
PASI score over time 
Secondary 
IGA mod 2011 score over time 
Secondary 
Start of relapse 
Secondary 
Time to relapse 
Secondary 
Rebound 
Secondary 
DLQI 0 or 1 achievement 
Secondary 
EQ-5D 
Secondary 
DLQI 
Secondary 
HAQ-DI score over time1 
Exploratory 


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Variable 
Type 
HAQ-DI response over time1 
Exploratory 
 
 
1only for subjects with psoriatic arthritis (PsA) at baseline of core study 
1.8.1.1 
Definition of PASI and related variables  
The total BSA affected by plaque-type psoriasis was estimated from the percentages of areas 
affected, including head, trunk, upper limbs and lower limbs (see below for PASI assessment).  
The following calculations were done: each reported percentage was 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 plaque-
type psoriasis.  The PASI scoring system is further described in Table 1-11. 
A PASI score (Fredriksson and Pettersson 1978, Weisman et al 2003, Gottlieb et al 2005) was 
derived as indicated in Table 1-11.  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 four 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 help the assessment: 
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 body surface area, respectively, the PASI score was 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, 
where E, I, D, and A denote erythema, induration, desquamation, and area, respectively, and h, 
u, t, and l denote head, upper extremities, trunk, and lower extremities, respectively (see Table 
1-11). 
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 investigator was only responsible for collecting the components or scoring signs and total 
regional area.  PASI calculations were done via the PASI Score eCRF.   
The PASI scores calculated via the PASI Score eCRF will be used in the analysis and for 
derivation of PASI response values, relapse and rebound (see below).  


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Table 1-11 
The PASI scoring system 
Body region 
Erythema (E) 
Thickening (I) 
(plaque 
elevation, 
induration) 
Scaling (D) 
(desquamation) 
Area score (A) 
(based on true area %)* 
Head (H)† 
0 = none 
0 = none 
0 = none 
0 = no involvement 
 
1 = slight 
1 = slight 
1 = slight 
1 = > 0 - < 10 
 
2 = moderate 
2 = moderate 
2 = moderate 
2 = 10 - < 30 
 
3 = severe 
3 = severe 
3 = severe 
3 = 30 - < 50 
 
4 = very severe 
4 = very severe 
4 = very severe 
4 = 50 - < 70 
 
 
 
 
5 = 70 - < 90 
 
 
 
 
6 = 90 – 100 
Trunk (T)‡ 
0 = none 
0 = none 
0 = none 
0 = no involvement 
 
1 = slight 
1 = slight 
1 = slight 
1 = > 0 - < 10 
 
2 = moderate 
2 = moderate 
2 = moderate 
2 = 10 - < 30 
 
3 = severe 
3 = severe 
3 = severe 
3 = 30 - < 50 
 
4 = very severe 
4 = very severe 
4 = very severe 
4 = 50 - < 70 
 
 
 
 
5 = 70 - < 90 
 
 
 
 
6 = 90 – 100 
Upper limbs (U) 
0 = none 
0 = none 
0 = none 
0 = no involvement 
 
1 = slight 
1 = slight 
1 = slight 
1 = > 0 - < 10 
 
2 = moderate 
2 = moderate 
2 = moderate 
2 = 10  - < 30 
 
3 = severe 
3 = severe 
3 = severe 
3 = 30 - < 50 
 
4 = very severe 
4 = very severe 
4 = very severe 
4 = 50 - < 70 
 
 
 
 
5 = 70 - < 90 
 
 
 
 
6 =  90 – 100 
Lower limb (L)§ 
0 = none 
0 = none 
0 = none 
0 = no involvement 
 
1 = slight 
1 = slight 
1 = slight 
1 = > 0 - < 10 
 
2 = moderate 
2 = moderate 
2 = moderate 
2 = 10 - < 30 
 
3 = severe 
3 = severe 
3 = severe 
3 = 30 - < 50 
 
4 = very severe 
4 = very severe 
4 = very severe 
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. 
The following definitions are possible efficacy evaluations that can be used in clinical trials in 
psoriasis (CHMP/EWP/2454/02, 2004):  
• PASI 50 response: subjects achieving ≥ 50% improvement (reduction) in PASI score  
compared to baseline are defined as PASI 50 responders 
• PASI 75 response: subjects achieving ≥ 75% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 75 responders 
• PASI 90 response: subjects achieving ≥ 90% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 90 responders 


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• PASI 100 response: complete clearing of psoriasis (PASI=0) 
Definition of IGA mod 2011 score and IGA mod 2011 0 or 1 response 
The IGA mod 2011 rating scale for overall psoriatic disease (shown in Table 1-12) has been 
developed based on a previous version of the scale used in secukinumab phase II studies, and 
has been updated in collaboration with health authorities (in particular the FDA. ).The 
explanations/descriptions of the points on the scale have been improved to ensure appropriate 
differentiation between the points. 
The IGA mod 2011 used in this study is static, i.e., it refers exclusively to the subject’s disease 
state at the time of the assessments, and does not attempt a comparison with any of the subject’s 
previous disease states, whether at baseline or at a previous visit. 
Table 1-12 
The IGA mod 2011 rating scale 
Score 
Short Description 
Detailed Description 
0 
Clear 
No signs of psoriasis. Post-inflammatory hyperpigmentation may 
be present. 
1 
Almost clear 
Normal to pink coloration of lesions; no thickening; no to minimal 
focal scaling. 
2 
Mild 
Pink to light red coloration; just detectable to mild thickening; 
predominantly fine scaling. 
3 
Moderate 
Dull bright red, clearly distinguishable erythema; clearly 
distinguishable to moderate thickening; moderate scaling. 
4 
Severe 
Bright to deep dark red coloration; severe thickening with hard 
edges; severe / coarse scaling covering almost all or all lesions. 
Note:  Involvement of nails is not part of the assessment. 
Based on this scale, subjects will be considered as IGA mod 2011 0 or 1 responder if they 
achieve a score of 0 or 1 and improve by at least 2 points on the IGA scale compared to baseline. 
1.8.1.2 
Health Assessment Questionnaire - Disability Index (HAQ-DI) 
The Health Assessment Questionnaire (HAQ©) was developed by Stanford University and is 
one of the most widely used measures to assess the long-term influence of chronic disease on a 
subject's level of functional ability and activity restriction. The disability assessment component 
of the HAQ (Health Assessment Questionnaire – Disability Index), the HAQ-DI, assesses a 
subject's level of functional ability and includes questions of fine movements of the upper 
extremity, locomotor activities of the lower extremity, and activities that involve both upper 
and lower extremities. There are 20 questions in eight categories of functioning including 
dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The stem of each 
item asks over the past week "Are you able to …" perform a particular task. Each item is scored 
on a 4-point scale from 0 to 3, representing normal (normal, no difficulty [0]), some difficulty 
[1], much difficulty [2], and unable to do [3].  
Scoring for the eight functional categories and overall disability index scoring will be performed 
as follows:  
There are eight categories; first score within each category:  


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 
Dressing and Grooming, includes items 1 and 2  
 
Arising, includes items 3 and 4  
 
Eating, includes items 5, 6 and 7  
 
Walking, includes items 8 and 9  
 
Hygiene, includes items 10, 11, and 12  
 
Reach, includes items 13 and 14  
 
Grip, includes items 15, 16 and 17  
 
Activities, includes items 18, 19, and 20 
The score for each category will be the single response within the category with the highest 
score (greatest difficulty). For example, in the "Eating" category, there are two answers (one 
for each item). If "Cut your food with a knife or fork" is marked as "3" and "Lift a full cup or 
glass to your mouth" is marked as "0", then the score for the "Eating" category would be "3" 
(the response indicating the greatest difficulty within the category). If a component question is 
left blank or the response is too ambiguous to assign a score, then the score that that category 
will be determined by the remaining completed question(s). However, if any "aids or devices" 
and/or "help from another person" items at the bottom of each page are checked with the 
exception of “other”, the category to which they apply will be adjusted upward to "2". If the 
basic score is already "2" or "3", the score remains unchanged. "Aids or devices" and "help 
from another person" can only change a category's score to "2"; they do not change the score to 
a "1" or a "3". Companion aids/devices items for HAQ-DI categories are presented in Table 1-
13. No score will be adjusted for “other” ticked, regardless of the “other” specification. 
The score for the disability index will be the mean of the eight category scores. If more than 
two of the categories, or 25%, are missing, scale will not be scored. If fewer than 2 of the 
categories are missing, divide the sum of the categories by the number of answered categories. 
The higher score indicates greater disability. 
HAQ-DI response is defined by an improvement of at least 0.3 score points compared to 
baseline. 


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Table 1-13 
Companion aids/devices items for HAQ-DI categories 
HAQ-DI Category  
Companion Item  
Dressing & Grooming   
Devices used for dressing (button hook, zipper pull, long handled 
shoe horn etc.)   
Arising   
Built up or special chair   
Eating   
Built up or special utensils   
Walking   
Cane walker, crutches   
Hygiene   
Raised toilet seat, bathtub seat, bathtub bar   
Long handled appliances in bathroom   
Reach   
Long handled appliances for reach   
Grip   
Jar opener (for jars previously opened)  
1.8.1.3 
Overview of analysis methods of efficacy variables 
An overview of statistical analyses and methods applied to psoriasis efficacy variables is given 
in Table 1-14 
Table 1-14 
Overview of analysis methods for efficacy variables 
Variable(s) 
Summary 
statistics 
for binary/ 
categorical 
data  
Summary 
statistics 
for 
continuous 
data 
Graphs 
Maintenance of response 
X 
 
 
PASI 50/75/90/100 response 
over time 
X 
 
X 
Absolute PASI score over 
time 
 
X 
 
Absolute change and % 
change PASI over time 
 
X 
 
IGA mod 2011 0 or 1 
response over time 
X 
 
X 
IGA mod 2011 score over 
time 
 
X 
 
Relapse 
X 
 
 
Rebound 
X 
 
 
EQ-5D 
X 
X 
 
Absolute DLQI 
 
X 
 
% change DLQI 
 
X 
 
DLQI 0 or 1 achievement 
X 
 
 
HAQ-DI score over time 
 
X1 
 
HAQ-DI response over time 
X1 
 
 
1only for subjects with psoriatic arthritis (PsA) at baseline of core study 


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1.8.2 
Statistical hypothesis, model, and method of analysis 
Not applicable. 
1.8.3 
Testing strategy 
No formal hypothesis testing will be performed for this extension study. 
1.8.4 
Handling of missing values/censoring/discontinuations 
As observed value (Follow-up assessment excluded) will be reported primarily for both efficacy 
and PROs.  
Response variables based on PASI score  and IGA mod 2011 categories will be imputed with 
multiple imputation (MI) (Follow-up assessment excluded) as secondary analysis method. 
Summary tables for PASI scores and IGA mod 2011 categories will also be imputed using MI. 
Other response variables (e.g. DLQI 0 or 1 achievement) will be imputed with LOCF (Follow-
up assessment excluded).  
1.8.4.1 
Multiple imputations for response  
The number of imputations will be set to 100 the seed for the random function will be set to 
4572304 for this study. 
Multiple imputation (MI) is a simulation based approach where missing values are replaced by 
multiple Bayesian draws from the conditional distribution of missing data given the observed 
data and covariates, creating multiple completed data sets. These completed data sets can then 
be analyzed using standard methods. Within this analysis the PASI score change from baseline 
or IGA mod 2011 categories will be imputed separately and response variables will be derived 
based on the imputed scores. In the multiple imputation analysis the response status will be 
imputed based on the individual treatment arm information. 
Of note: subjects with missing baseline or subjects with all post-baseline missing will be 
included in the multiple imputation analysis. 
1.8.5 
Supportive analyses 
Not applicable. 
1.8.6 
Secondary variables 
1.8.7 
Methods of analysis 
 
Maintenance of response 
Maintenance of response is defined as follows: 
• for subjects in the fixed interval regimens, maintenance of response is defined as 
PASI 75 response at Weeks 104 and 156  
• for subjects in the start of relapse regimens maintenance of response is defined as  


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• PASI 75 response at Weeks 92 and 144 for subjects who do not require active 
treatment at Week 92 or 144 and 
• PASI 75 response at Weeks 104 and 156 for subjects who do require active treatment 
at Week 92 or 144. 
 
Summary statistics of Maintenance of response will be presented in contingency tables and will 
include absolute and relative frequencies. Confidence intervals for response rates will be 
derived as well based on the score method including continuity correction (Newcombe 1998). 
 
PASI 50, PASI 75, PASI 90, PASI 100 and IGA 0 or 1 response over time 
Summary statistics for PASI 50, PASI 75, PASI 90, PASI 100, and IGA mod 2011 0 or 1 
response by analysis visit will be presented in contingency tables and will include absolute and 
relative frequencies. Confidence intervals for response rates will be derived as well based on 
the score method including continuity correction (Newcombe 1998). 
 
PASI score over time 
Summary statistics will be provided for absolute PASI scores as well as for absolute change 
and 
percent 
change 
from 
baseline 
by 
analysis 
visit 
and 
treatment 
group.  
 
IGA mod 2011 score over time 
Summary statistics for the IGA mod 2011 score over time will be presented by analysis visit 
and treatment group in contingency tables. 
 
Relapse 
The number and percentage of subjects experience relapse will be presented by treatment 
group and visit. 
Rebound or rebound like events 
The number and percentage of subjects experiencing rebound or rebound like events will be 
presented by treatment group as follows: 
• For rebound, all assessments done up to 8 weeks after last injection will be summarized.  
• Similarly for rebound like events, all assessments done up to 12 weeks after last injection 
will be summarized. 
Subjects who received commercially available Cosentyx® will be excluded from this 
analysis.   
1.8.8 
Exploratory analyses 
 
Psoriatic arthritis 
Summary statistics will be provided for HAQ-DI score and HAQ-DI response over time for all 
subjects with psoriatic arthritis recorded on the Psoriatic Arthritis History eCRF at screening.  


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1.8.9 
Biomarkers 
Not applicable. 
1.8.10 
Health-related Quality of Life (HRQoL) 
Summaries will be based on the FAS and will be presented separately for study periods if not 
specified otherwise. 
Dermatology Life Quality Index  
The DLQI measures functional disability of subjects with dermatological disorders that are 
greater than 18 years of age and had been utilized as a relevant clinical measure in atopic 
dermatitis, as well as other dermatitis clinical trials. The DLQI is a simple, validated, self-
administered 10-item questionnaire. The instrument contains six functional scales (i.e., 
symptoms and feeling, daily activities, leisure, work and school, personal relationships, 
treatment).  For the DLQI, each question will be answered with the following response: “not at 
all,” “a little,” “a lot,” or “very much”. Seven scores will be derived from the DLQI: the total 
score of each of the six dimensions as well as the total score over all items. The higher the score, 
the more quality of life is impaired.  
In addition, summary statistics will be provided for number of subjects achieving DLQI 0 or 1.  
Output shells in MAP module 7.1: T_DLQIANA3 


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EQ-5D 
The EQ-5D is a questionnaire with 5 questions  each with three categories (no problem, 
moderate problem, severe problems) and a health state assessment from 0 (worst possible health 
state) to 100 (best possible health state). The number and percentage of subjects in each of the 
three categories for each question will be presented by analysis visit and treatment group.  
Summary statistics will be shown for the health state assessment by analysis visit and treatment 
group.  
HAQ©-DI (for subjects with PSA at baseline of the core study) 
Summary statistics will be derived for HAQ©-DI score over time for all subjects with 
psoriatic arthritis recorded on the Psoriatic Arthritis History eCRF at screening visit of the 
core study. 
Absolute and relative frequencies for HAQ©-DI response will also be presented. HAQ©-DI 
response is defined by an improvement of 0.3 score points compared to baseline. 
 
1.9 
Standard safety evaluation 
All safety analyses will be based on the safety set. Core study baseline will be used for all 
change from baseline analysis. 
Absolute and relative frequencies and exposure time adjusted incidence rate or event rate 
analysis will consider all the events (AEs/SAEs and clinically significant newly occurring lab, 
vitals and ECG abnormalities) that occurred in core studies and extension study for entire 
treatment period and in extension study for treatment period in E1. 
Safety analyses will be performed on treatment received or actual treatment (See Section 1.2). 
1.9.1 
Adverse events 
Treatment emergent adverse are defined as events started after the first dose of study medication 
or events present prior to the first dose of study medication but increased in severity after dosing 
based on preferred term and within last dose + 84 days or last visit date of follow-up 1 period 
which comes earlier. Only treatment emergent adverse events are summarized 
The crude incidence of treatment emergent adverse events will be presented for the entire 
treatment period and also by yearly interval (365 days) for 150 and 300 mg FI cohorts. The 
crude incidence of treatment emergent adverse events will be summarized by primary System 
Organ Class (SOC) and Preferred Term (PT). Confidence intervals for the crude rate will be 
derived as described in Section 2.3.1. In addition, exposure time-adjusted incidence rates 
including 95% confidence intervals will be provided for the entire treatment period by yearly 
interval (365 days) for 150 and 300 mg FI cohorts. 
Please note that exposure adjusted incidence rates will be provided and follow the guideline as 
below: 
• Primary SOC level for AE and SAE 
• Level 1 for risks and SMQ 


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• PT level for SAE 
• PT level for AE ≥ 2%, or events that had an incidence rate of at least 5.0 cases per 
100 subject-years in  one of any AIN457 XXX mg  
• Other selected AEs on lower levels (e.g. PT or SMQ level 2), if appropriate 
• Special AE interest: 
•  
Special AE interest: 
Notes (All levels are displayed) 
Inflammatory bowel disease (NMQ) (narrow) 
Include Crohns (PT) and Ulcerative colitis 
(PT) and others 
Opportunistic infections (NMQ) 
Candida infections (HLT) 
Herpes viral infections (HLT) 
Both Oral and other are included 
Staphylococcal infections (HLT) 
MACE (MI, Stroke, Cardiovascular death) (NMQ) 
Cardio-cerebrovascular-related events (NMQ) 
Malignant or unspecified tumours (SMQ) 
Including BCC, SCC in SMQ 
Malignant or unspecified tumours (SMQ excl BCC and SCC) 
(NMQ) 
Upper respiratory tract infections (HLT) 
 
Adverse events will be summarized by presenting, for each treatment group (including “any 
AIN457”), the number and percentage of subjects having at least one AE at each year interval 
(for 150 and 300 mg FI cohorts), having an AE in each primary system organ class and having 
each individual AE (preferred term). Summaries will also be presented for AEs by severity and 
for study treatment related AEs. If a particular AE ‘severity’ is missing, this variable will be 
listed as missing and treated as missing in summaries. If a subject reported more than one 
adverse event with the same preferred term, the adverse event with the greatest severity will be 
presented. If a subject reported more than one adverse event within the same primary system 
organ class, the subject will be counted only once with the greatest severity at the system organ 
class level, where applicable.  
The most common adverse events reported (≥ z % in any group for each preferred term in the 
table by SOC and PT or ≥ z % in any group for each SMQ table) will be presented in descending 
frequency according to its incidence in total secukinumab group (combining all secukinumab 
treatment groups) starting from the most common event. Here threshold value z is set to 1 (%) 
but it may be updated following review of the dry run outputs. 
Adverse events that started in core studies before the first dose of the study treatment in 
extension and continued into extension will not be included in the on treatment in E1 tables. 
Separate summaries will be provided for deaths, serious adverse events, other significant 
adverse events leading to discontinuation and adverse events leading to dose adjustment. 
Adverse events will also be summarized by SMQ according to MedDRA. 
Exposure time will be derived as following: 


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• Starting day: is the first study day of each period (Day 1 for year 1, Day 366 for year 1-
2, etc.,) 
• Ending day:   
o For patients with events: first AE onset day within each interval (worsening is 
not considered between the yearly interval) or first lab event assessment day 
o For patients without any event during the interval:  
i. Censored day for AEs is defined as min [end of period day (i.e., day 365 
for year 1, day 730 for year 1-2, etc.,), or min(last visit day, last dose + 
84 days) for early discontinued subjects, or switched date] 
ii. Censored day for Labs will be end of period day (i.e, day 365 for year1, 
day 730 for year 1-2, etc., ) for ongoing patients or the last assessment 
day within each interval. 
The MedDRA version used for reporting the adverse events will be described in a footnote. 
listings of all adverse events will be done based on entire study period and follow-up 2 period 
separately. A column indicating if the adverse event is treatment emergent or not will be shown. 
Non-treatment emergent adverse events may be summarized separately upon request. 
Algorithms for date imputations will be provided in RAP M8. 
 
1.9.2 
Laboratory data 
All the summaries of lab data (newly occurring notables, shift tables, by visit summaries, 
maximum changes if required) will only include data during treatment period, which are defined 
as those lab assessments within last dose plus 84 days or last visit of follow up period which 
comes earlier.  
The laboratory values below Lower Level Of Quantification (LLQ) or above Upper Level of 
Quantification (ULQ)  will be imputed as LLQ or ULQ, respectively. The numerical part of the 
reported result will be treated as  the actual LLQ or ULQ  . These laboratory values will be 
displayed in listings using the standard unit with the reported sign (“<” or “>”).” 
All the listings of lab data will include all records with an on-treatment flag, i.e., a yes-or-no 
flag indicating whether the record occurred within last dose plus 84 days. 
The summary of laboratory evaluations will be presented for two groups of laboratory tests 
(hematology, clinical chemistry and urinalysis). In addition to the individual laboratory 
parameters, the ratios “total cholesterol / HDL” and “apolipoprotein B / apolipoprotein A1” will 
be derived and summarized. 
Descriptive summary statistics for the change from baseline to each study visit will be presented 
by laboratory test and treatment group. Change from baseline will only be summarized for 
subjects with both baseline and post baseline values and will be calculated as: 
change from baseline = post baseline value – baseline value 


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For each parameter, the maximum change (maximum decrease and maximum increase) from 
baseline will be analyzed analogously.  
In addition, shift tables will be provided for all parameters to compare a subject’s baseline 
laboratory evaluation relative to the most extreme laboratory test value within the treatment 
period.  For the shift tables, the normal laboratory ranges will be used to evaluate whether a 
particular laboratory test value was normal, low, or high for each visit value relative to whether 
or not the baseline value was normal, low, or high (including category “high and low”).  These 
summaries will be presented by laboratory test and treatment group. 
The following laboratory parameters will be analyzed with respect to Common Terminology 
Criteria for Adverse Events (CTCAE) grades, given in Table 1-18: hemoglobin, platelets, white 
blood cell count, neutrophils lymphocytes, creatinine, total bilirubin (TBL), gamma-glutamyl 
transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphatase (ALP), glucose, cholesterol, triglycerides (TG). 
The number and percentage of subjects with clinically CTCAE grade newly occurring or 
worsening after baseline will be presented for the treatment period.  
Absolute and relative frequencies will be derived for non-overlap groups: CTCAE grade 1, 
CTCAE grade 2, CTCAE grade 3, and CTCAE grade 4; and exposure adjusted incidence rate 
will be derived for nesting groups: CTCAE grade >=1, CTCAE grade >=2, CTCAE grade >=3, 
CTCAE grade 4. 
Table 1-18 
CTCAE grades for laboratory parameters to be analyzed 
 
CTCAE v4.0 Term 
Grade 1    
Grade 2    
Grade 3    
Grade 4    
HGB decreased 
(Anemia) 
<LLN - 6.2 mmol/L 
<6.2 - 4.9 mmol/L 
<4.9 mmol/L 
 
Platelet count 
decreased 
<LLN – 75.0 x10e9 /L 
<75.0 - 50.0 x10e9 /L 
<50.0 – 25.0 x10e9 /L 
<25.0 x 10e9 /L 
White blood cell 
decreased 
<LLN - 3.0 x 10e9 /L 
<3.0 - 2.0 x 10e9 /L 
<2.0 - 1.0 x 10e9 /L 
<1.0 x 10e9 /L 
Neutrophil count 
decreased 
<LLN - 1.5 x 10e9 /L 
<1.5 - 1.0 x 10e9 /L 
<1.0 - 0.5 x 10e9 /L 
<0.5 x 10e9 /L 
Lymphocyte count 
decreased 
<LLN - 0.8 x 10e9/L 
<0.8 - 0.5 x 10e9 /L 
 
<0.5 - 0.2 x 10e9 /L 
<0.2 x 10e9 /L 
Creatinine increased* 
 
>1 - 1.5 x baseline;  
>ULN - 1.5 x ULN 
>1.5 - 3.0 x 
baseline; >1.5 - 3.0 x 
ULN 
>3.0 baseline;  
>3.0 - 6.0 x ULN 
>6.0 x ULN 
TBL increased 
>ULN - 1.5 x ULN 
>1.5 - 3.0 x ULN 
>3.0 - 10.0 x ULN 
>10.0 x ULN 
GGT increased 
>ULN - 2.5 x ULN 
>2.5 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
ALT increased 
>ULN - 3.0 x ULN 
>3.0 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
AST increased 
>ULN - 3.0 x ULN 
>3.0 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
ALP increased 
>ULN - 2.5 x ULN 
>2.5 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
Glucose increased 
(Hyperglycemia )  
;  
>ULN - 8.9 mmol/L 
>8.9 - 13.9 mmol/L 
>13.9 - 27.8 mmol/L 
>27.8 mmol/L 
Glucose decreased 
(Hypoglycemia) 
<LLN - 3.0 mmol/L 
<3.0 - 2.2 mmol/L 
<2.2 - 1.7 mmol/L 
<1.7 mmol/L 
Cholesterol high 
 
>ULN - 7.75 mmol/L 
>7.75 - 10.34 mmol/L 
>10.34 - 12.92 mmol/L 
>12.92 mmol/L 
Hypertriglyceridemia 
 
1.71 - 3.42 mmol/L 
>3.42 - 5.7mmol/L 
>5.7 - 11.4 mmol/L 
>11.4 mmol/L 


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*Note: for “creatinine increased” the baseline criteria do not apply 
Shift tables will be presented comparing baseline laboratory result (CTCAE grade) with the 
worst results (expressed in CTCAE grade) during the treatment phase (either initial or entire) 
analyzed. Of note, baseline will be defined as last assessment prior to first dosing in the core 
study. Subjects with abnormal laboratory values will be listed and values outside the normal 
ranges will be flagged. 
Exposure adjusted incidence rate for neutropenia CTCAE grade >= 2 will be presented for the 
entire treatment period. 
Summaries for newly occurring or worsening clinically notable lipid abnormalities will also be 
provided cumulatively for each of the following parameters and categories: 
• 
HDL: 
• 
<=LLN 
• 
<0.8 x LLN 
• 
LDL, cholesterol, triglycerides: 
• 
>=ULN  
• 
>1.5 x ULN  
• 
>2.5 x ULN 
Subjects with newly occurring or worsening after baseline abnormalities in lipid parameters 
will be listed. If a subject experiences newly occurring or worsening of abnormality for a 
parameter the entire time course of that parameter will be listed. 
Newly occurring liver enzyme abnormalities will also be summarized based on the event criteria 
given in Table 1-19. 


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Table 1-19 
Liver-related events 
Parameter 
Criterion 
ALT 
>3xULN; >5xULN; >8xULN;>10xULN, >20xULN 
AST 
>3xULN; >5xULN; >8xULN; >10xULN; >20xULN 
ALT or AST 
>3xULN; >5xULN; >8xULN; >10xULN; >20xULN 
TBL 
>1xULN; >1.5xULN; >2xULN; >3xULN, 
ALP 
>1.5xULN; >2xULN; >3xULN; >5xULN 
ALT or AST & 
TBL 
ALT or AST>3xULN & TBL >1.5xULN; 
ALT or AST>3xULN & TBL >2xULN; 
ALT or AST >5xULN & TBL >2xULN; 
ALT or AST >8xULN & TBL >2xULN; 
ALT or AST >10xULN & TBL >2xULN 
ALT or AST >20xULN & TBL >2xULN 
ALP & TBL 
ALP >3xULN & TBL >2xULN 
ALP >5xULN & TBL >2xULN 
ALT or AST & 
TBL & ALP 
ALT or AST>3xULN & TBL >2xULN & ALP ≤2xULN  (Potential Hy’s Law) 
Note: elevated ALP may suggest obstruction as a consequence of gall bladder or 
bile duct disease; ALP may also be increased in malignancy. FDA therefore terms 
Hy’s Law cases as indicators of pure hepatocellular injury. This does not mean 
that cases of ALT or AST >3xULN & TBL >2xULN & ALP >2xULN may not result 
in severe DILI. 
 
Notes: 
1) In studies which enroll subjects with pre-existing liver disease, baseline LFT may be increased 
above ULN; in such a case it is meaningful to add the condition “and worse than baseline” to the 
abnormality criteria 
2) In case an Adjudication Committee is in place it may be meaningful to summarize all abnormalities 
classed as e.g., definitely/probably (depending on the categories used) related to study treatment 
For a combined criterion to be fulfilled, all conditions have to be fulfilled on the same visit. The 
criteria are not mutually exclusive, e.g., a subject with ALT = 6.42xULN is counted for 
ALT >3xULN and ALT>5x ULN. 
Individual subject data listings will be provided for subjects with abnormal laboratory data. 
Data of subjects with newly occurring liver enzyme abnormalities will be listed in an additional 
listing. 
 
1.9.3 
Vital signs 
All the summaries of vital signs will only include data during treatment period, which are 
defined as those lab assessments within last dose plus 84 days or last visit of follow up period 
which comes earlier. 
All the listings of vital signs will include all records with an on-treatment flag, i.e., a yes-or-no 
flag indicating whether the record occurred within last dose plus 84 days. 
Analysis in vital sign measurement using descriptive summary statistics for the change from 
baseline for each post-baseline visit will be performed by vital sign and treatment group. 


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Change from baseline will only be summarized for subjects with both baseline and post-baseline 
values and will be calculated as: 
change from baseline = post-baseline value – baseline value 
The number and percentage of subjects with newly occurring notable vital signs will be 
presented.  Clinically notable vital sign results are provided in Table 1-20 below. The crude 
incidence for the treatment period will be shown for entire treatment period.  
Table 1-20 
Criteria for notable vital sign abnormalities 
Vital sign (unit) 
Notable abnormalities 
Systolic blood pressure (mmHg) 
>= 140 mmHg or < 90 mmHg 
Diastolic blood pressure (mmHg) 
>=90 mmHg or <60 mmHg 
Pulse (bpm) 
> 100 bpm or <60 bpm 
1.9.4 
Electrocardiogram (ECG) 
All the summaries of ECG will only include data during treatment period, which are defined as 
those lab assessments within last dose plus 84 days or last visit of follow up period which comes 
earlier. 
All the listings of ECG will include all records with an on-treatment flag, i.e., a yes-or-no flag 
indicating whether the record occurred within last dose plus 84 days. 
The following quantitative variables will be summarized: ventricular rate, RR interval, PR 
interval, QRS duration, QT interval, and corrected QT interval (QTc). Both Bazett (QTcB) and 
Fridericia (QTcF) corrections will be presented for QTc.  
QTc will be summarized by computing the number and percentage of subjects with: 
• QTc > 500 msec  
• QTc > 480 msec 
• QTc > 450 msec 
• QTc changes from baseline > 30 msec 
• QTc changes from baseline > 60 msec 
• Sinus pause > 3 sec, if appropriate 
• PR > 250 msec 
Summary statistics will be presented for ECG variables by analysis visit and treatment group. 
In addition, shift tables comparing baseline ECG results (normal, abnormal, not available, total) 
with the maximum on-study result (normal, abnormal, not available, total) will be provided. 
A listing of all newly occurring or worsening abnormalities will be provided, as well as a by-
subject listing of all quantitative ECG parameters.   
1.9.5 
Immunogenicity 
 A listing of immunogenicity data will be provided. 


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1.10 
Sample size calculation 
Not applicable. 
1.11 
Power for analysis of key secondary variables 
Not applicable. 
1.12 
Interim analyses 
Four interim analyses have been done, first one at the time of 120 days safety update; second 
one for 3 years IA; third one for 4 years IA; and one for 5 years IA. 


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2 
Clinical Study Report -  
Appendix 16.1.9 Documentation of statistical methods 
Summary statistics for continuous variables will include N, mean, standard deviation, minimum, 
lower quartile, median, upper quartile, maximum.  
Summary statistics for discrete variables will be presented in contingency tables and will 
include absolute and relative frequencies. 
2.1 
Analysis of continuous data 
Summary statistics (including N, mean, standard deviation, minimum, lower quartile, median, 
upper quartile, maximum) will be provided for continuous data by visit and treatment group. 
For PASI score, DLQI total score, HAQ-DI summary statistics will be derived for absolute and 
percentage changes from baseline.  
2.2 
Analysis of binary (and categorical) data 
2.2.1 
Summary statistics for binary and categorical data 
Summary statistics for discrete variables will be presented in contingency tables and will 
include absolute and relative frequencies. If applicable, confidence intervals will be derived as 
well based on the score method including continuity correction [Newcombe 1998]: 
With z as (1-alpha/2)-quantile of the standard normal distribution (SAS: z=PROBIT(1-
alpha/2), n  as total number of subjects (i.e. number of subjects in the denominator), and p as 
estimated crude incidence (number of subjects with event / n ) it is 
 
Then the lower limit is for 
 
(
)
(
)










+
+
+
−
−
−
−
+
=
2
2
2
2
1
4
1
2
1
2
,0
max
z
n
nq
p
n
z
z
z
np
L
 
and the upper limit is for 
 
(
)
(
)










+
−
+
−
+
+
+
+
=
2
2
2
2
1
4
1
2
1
2
,1
min
z
n
nq
p
n
z
z
z
np
U
. 
For time courses of response variables, the point estimate at each time point including 95% 
confidence interval will be plotted. 
2.2.2 
Multiple imputations for response variables 
In the multiple imputations analysis the response status will be imputed based on the individual 
treatment arm information. 
In case of higher drop-out rates or higher study treatment discontinuations for reasons other 
than lack of efficacy additional sensitivity analyses will be performed. 
p
q
−
=1
(
),
0
for
0
,0
=
=
>
p
L
p
(
),
1
for
1
,1
=
=
<
p
U
p


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Multiple imputation (MI) is a simulation based approach where missing values are replaced by 
multiple Bayesian draws from the conditional distribution of missing data given the observed 
data and covariates, creating multiple completed data sets. These completed data sets can then 
be analyzed using standard methods. Rubin (1987) presented rules how to combine the multiple 
sets of estimates to produce overall estimates and confidence intervals that adequately 
incorporate missing data uncertainty.  
Missing values for the ‘change from baseline PASI score’ and ‘IGA mod 2011 score’ will be 
imputed simultaneously based on an underlying joint normal distribution and using a Markov 
Chain Monte Carlo (MCMC) method. The change from baseline in PASI score appears to 
follow closer to a normal distribution than the actual PASI score. Assuming normality for the 
‘IGA mod 2011 score’ is motivated by Schaefer (1997), where it was shown that the 
multivariate normal approximation for the imputation of incomplete categorical and binary data 
is robust.  
The imputations will be done separately for each treatment group including baseline weight, 
failure to at least one previous biologic (yes/no), and number of previous systemic therapies as 
additional covariates.  
The number of imputations will be set to 100, the seed for the random function will be set to 
4572304 for this study. To generate the multiple imputed data sets, the SAS procedure MI can 
be used as follows: 
The input data set <pasi_in> should have one record per subject with baseline PASI score and 
IGA mod 2011 score as well as all changes from baseline PASI and post-baseline IGA mod 
2011 score. 
 
ODS LISTING CLOSE; 
ODS OUTPUT MissPattern=msgpat VarianceInfo=varinfo ParameterEstimates=param; 
PROC MI DATA=<pasi_in> OUT=<impdata> SEED=457<studycode> NIMPUTE=100; 
 VAR <baseline weight> <failure to at least one biologic>  
     <number of previous systemic therapies>  
     <baseline PASI>  
     <change from baseline PASI week 1> - <change from baseline PASI week primary endpoint>； 
  BY <treatment group>; 
RUN; 
ODS LISTING; 
 
Programming notes: 
• The SAS procedure MIANALYZE expects a variable called “_IMPUTATION_ which 
is generated by the MI procedure. It might be needed to set the SAS option 
“VALIDVARNAME=UPCASE” temporarily in the program before the MI call, this 
option should be reset after the MIANALYZE call to VALIDVARNAME=V6.  
• In case there are no missings in one treatment group, the MI procedure does not 
impute any values. In this case the corresponding data need to be imputed manually 
outside PROC MI and added to the dataset <impdata>. 
 
The imputed data are saved in data set <impdata>. The outcomes of interest, i.e. the PASI 
50/75/90/100 response and IGA mod 2011 0 or 1 response will be calculated, e.g. as follows: 


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DATA <impdata2>; 
 SET <impdata>; 
IF <change from baseline PASI week primary endpoint>/<baseline PASI>=0.90 THEN <PASI 90 response> =1; 
ELSE <PASI 90 response>=0; 
<…repeat for all PASI response…> 
 
IF <baseline IGA> >=3 THEN DO; 
 
     IF <IGA week primary endpoint> < 1.5 THEN <IGA 0/1 response> =1; 
 
ELSE IF <IGA week primary endpoint> >=1.5 THEN <IGA 0/1 response> =0; 
 
ELSE PUT "E" "RROR:" stysid1a=; 
END; 
ELSE IF <baseline IGA>=2 THEN DO; 
 
     IF <IGA week primary endpoint> < 0.5 THEN <IGA 0/1 response> =1; 
 
ELSE IF <IGA week primary endpoint> >=0.5 THEN <IGA 0/1 response> =0; 
 
ELSE PUT "E" "RROR:" stysid1a=; 
END; 
ELSE <IGA 0/1 response> =0; 
RUN; 
2.3 
Crude incidence and related risk estimates  
2.3.1 
Crude incidence and 100*(1-α)% confidence interval 
For n subjects, each at risk to experience a certain event with probability π, the crude incidence 
is estimated as p=x/n, where x is the number of subjects with the event. 
Absolute and relative frequencies will be displayed as well as 95% confidence interval for the 
relative frequency based on the score method including continuity correction (Newcombe 1998).  
With z  as (1-α/2)-quantile of the standard normal distribution (SAS: z=PROBIT(1-alpha/2), 
n  as total number of subjects (i.e. number of subjects in the denominator), and p as estimated 
crude incidence (number of subjects with event / n ) it is 
. 
Then the lower limit is 
(
)
(
)










+
+
+
−
−
−
−
+
=
2
2
2
2
1
4
1
2
1
2
,0
max
z
n
nq
p
n
z
z
z
np
L
 
and the upper limit is 
(
)
(
)










+
−
+
−
+
+
+
+
=
2
2
2
2
1
4
1
2
1
2
,1
min
z
n
nq
p
n
z
z
z
np
U
. 
 
Note: if p = 0 then L = 0 and if p = 1 then U = 1. 
If appropriate, an exact 100*(1-α)% confidence interval (Clopper-Pearson 1934) will be 
obtained by using the SAS procedure PROC FREQ with the EXACT BINOMIAL statement. 
p
q
−
=1


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However, the confidence interval derived via the score method including continuity correction 
will be the default in safety analyses. 
2.4 
Exposure adjusted incidence rate and related risk estimates 
2.4.1 
Exposure adjusted incidence rate and 100*(1-α)% confidence interval 
It will be assumed that for each of n subjects in a clinical trial the time tj (j=1,...,n) to the first 
occurrence of a certain treatment emergent event is observed, or if the event was not 
experienced, the (censored) time to the end of the observation period or last dose plus 84 days 
whichever occur earlier. The sequence of first occurrences of an event will be modeled to follow 
approximately a Poisson process with constant intensity θ. The rate parameter θ will be 
estimated as λ=D/T, where 
∑
=
=
n
j
jt
T
1
and D is the number of subjects with at least one event. 
Conditionally on T, an exact 100*(1-α)% confidence interval for a Poisson variable with 
parameter θT and observed value D can be obtained based on (Garwood, 1936), from which an 
exact 100*(1-α)% confidence interval for D/T will be derived as follows (Sahai, 1993; Ulm, 
1990): 
Lower confidence limit   
 for D>0, 0 otherwise, 
Upper confidence limit 
 
where
k
c ,
α
 is the αth quantile of the Chi-square distribution with k degrees of freedom. 
2.5 
Subject reported outcomes 
2.5.1 
Dermatology Life Quality Index (DLQI) 
The DLQI is a 10-item general dermatology disability index designed to assess Health-related 
quality of life in adult subjects with skin diseases (e.g. psoriasis). The measure is self-
administered and includes six domains of symptoms and feelings, daily activities, leisure, work 
and school, personal relationships and treatment. 
The scoring of each question is as follows: 
• Very much : Scored 3 
• A lot: Scored 2 
• A little: Scored 1 
• Not at all: Scored 0 
• Not relevant: Scored 0 
• Question unanswered: Scored 0 
• Question 7: "prevented work or studying": Scored 3 
T
c
L
D
2
,2
/
5.0
α
=
T
c
U
D 2
2
,2
/
1
5.0
+
−
=
α


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The DLQI total score will be calculated by summing the score of each question resulting in a 
maximum of 30 and a minimum of 0. The higher the score, the more Quality of Life is impaired.  
Meaning of DLQI Scores: 
• 0-1= no effect at all on subject's life 
• 2-5= small effect on subject's life 
• 6-10= moderate effect on subject's life 
• 11-20= very large effect on subject's life 
• 21-30= extremely large effect on subject's life 
The DLQI will be analyzed under six headings as follows: 
• Symptoms and feelings: questions 1 and 2, score maximum 6 
• Daily activities: questions 3 and 4, score maximum 6 
• Leisure: questions 5 and 6, score maximum 6 
• Work and school : question 7, score maximum 3 
• Personal relationships: questions 8 and 9: score maximum 6 
• Treatment: question 10, score maximum 3 
Interpretation of incorrectly completed questionnaires: 
There is a very high success rate of accurate completion of the DLQI. However, sometimes 
subjects do make mistakes. 
1. If one question is left unanswered this is scored 0. 
2. If two or more questions are left unanswered the questionnaire will not be scored. 
3. If question 7 is answered 'yes' this will be scored 3. If question 7 will be answered 'no' or 
'not relevant' but then either 'a lot' or 'a little' is ticked this will then be scored 2 or 1, 
respectively. 
4. If two or more response options are ticked, the response option with the highest score will 
be recorded. 
5. If there is a response between two tick boxes, the lower of the two score options will be 
recorded. 
6. If one item is missing from a two- item subscale that subscale will not be scored. 
Handling of missing values: 
• If there is only one missing score per visit, it will be imputed with 0, and then the subscale 
including this item and the total score are derived accordingly. 
• If there are two or more missing scores per visit, LOCF will be applied to the individual 
question scores, subscale scores, and total score, separately (i.e. LOCF is NOT applied to 
the 10 individual question scores for further derivation of the 6 subscale scores and 1 total 
score). 


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Of note, in situations where subjects responded to more questions than what was expected or 
required, the “most severe” answer was entered into the WriteResult (vendor for PRO data) 
database. In most cases the Self-Evident Corrections (SECs) were defined correctly, however, 
the SEC regarding question 7A/7B was not designed to select the “most severe” answer. This 
was confirmed with Novartis HEOR and communicated to the AIN team. 
2.5.2 
EQ-5D 
The EQ-5D is a generic instrument developed by the EuroQoL group to assess subject’s health 
status for clinical and economic appraisal. The instrument essentially consists of two pages – 
the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The EQ-5D descriptive 
system comprises the following five dimensions: mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression. 
Each dimension has three response levels: no problems, some problems, severe problem. The 
subject is asked to indicate the subject’s health state by ticking in the box against the most 
appropriate statement in each of the five dimensions. 
The VAS records the respondent’s self-rated health on a vertical 20-cm visual analogue scale 
where the endpoints are labeled ‘Best imaginable health state’ and ‘Worst imaginable health 
state’. Health Assessment Questionnaire - Disability Index (HAQ-DI) 
The Health Assessment Questionnaire (HAQ©) was developed by Stanford University. The 
disability assessment component of the HAQ, the HAQ-DI (Health Assessment Questionnaire 
– Disability Index), assesses a subject's level of functional ability and includes questions of fine 
movements of the upper extremity, locomotor activities of the lower extremity, and activities 
that involve both upper and lower extremities. There are 20 questions in eight categories of 
functioning including dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. 
The stem of each item asks over the past week "Are you able to …" perform a particular task. 
Each item is scored on a 4-point scale from 0 to 3, representing normal (normal, no difficulty 
[0]), some difficulty [1], much difficulty [2], and unable to do [3].  
Scoring for the eight functional categories and overall disability index scoring will be performed 
as follows:  
There are eight categories; first score within each category:  
 
Dressing and Grooming, includes items 1 and 2  
 
Arising, includes items 3 and 4  
 
Eating, includes items 5, 6 and 7  
 
Walking, includes items 8 and 9  
 
Hygiene, includes items 10, 11, and 12  
 
Reach, includes items 13 and 14  
 
Grip, includes items 15, 16 and 17  
 
Activities, includes items 18, 19, and 20 


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The score for each category will be the single response within the category with the highest 
score (greatest difficulty). For example, in the "Eating" category, there are two answers (one 
for each item). If "Cut your food with a knife or fork" is marked as "3" and "Lift a full cup or 
glass to your mouth" is marked as "0", then the score for the "Eating" category would be "3" 
(the response indicating the greatest difficulty within the category). If a component question is 
left blank or the response is too ambiguous to assign a score, then the score that that category 
will be determined by the remaining completed question(s). However, if any "aids or devices" 
and/or "help from another person" items at the bottom of each page are checked with the 
exception of “other”, the category to which they apply will be adjusted upward to "2". If the 
basic score is already "2" or "3", the score remains unchanged. "Aids or devices" and "help 
from another person" can only change a category's score to "2"; they do not change the score 
to a "1" or a "3". Companion aids/devices items for HAQ-DI categories are presented in Table 
2-2 
Companion aids/devices items for HAQ-DI categories 
. No score will be adjusted for “other” ticked, regardless of the “other” specification. 
The score for the disability index will be the mean of the eight category scores. If more than 
two of the categories, or 25%, are missing, scale will not be scored. If fewer than 2 of the 
categories are missing, divide the sum of the categories by the number of answered categories. 
The higher score indicates greater disability. 
HAQ-DI response is defined by an improvement of at least 0.3 score points compared to 
baseline. 
Table 2-2 
Companion aids/devices items for HAQ-DI categories 
HAQ-DI Category  
Companion Item  
Dressing & Grooming   
Devices used for dressing (button hook, zipper pull, long handled 
shoe horn etc.)   
Arising   
Built up or special chair   
Eating   
Built up or special utensils   
Walking   
Cane, walker, crutches, Wheelchair   
Hygiene   
Raised toilet seat, bathtub seat, bathtub bar   
Long handled appliances in bathroom   
Reach   
Long handled appliances for reach   
Grip   
Jar opener (for jars previously opened)  
 


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3 
References 
 
 
  
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
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Sahai H, Khurshid Anwer (1993). Confidence intervals for the mean of a poisson distribution: 
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Weisman S, Pollack CR, Gottschalk RW (2003) Psoriasis disease severity measures: 
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