Conditions: Psoriasis
Keywords: psoriasis secukinumab pre-filled syringes
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 214
Healthy volunteers: no

Brief summary:
The aim of the study was to demonstrate efficacy, safety and tolerability of 2 mL pre-filled syringe of 300 mg secukinumab in treatment of moderate to severe plaque psoriasis.

Detailed description:
This is a 52-weeks multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in 24 subjects with moderate to severe plaque-type psoriasis.

Arms:
arm 1: Placebo, provided in a 2 mL pre-filled syringe Placebo, provided in a 1 mL pre-filled syringe arm 2: Secukinumab 300 mg, provided in a 2 mL pre-filled syringe arm 3: Secukinumab 300 mg provided in 2 pre-filled syringes of 1 mL/150 mg (current approved form)

Interventions: intervention 1: Placebo intervention 2: Secukinumab 2 mL form intervention 3: Secukinumab 1 mL form
Intervention descriptions: intervention 1: 2 mL + 2 x 1 mL Placebo s.c. at randomization, weeks 1, 3, and 4, thereafter 4-weekly until week 48 intervention 2: Secukinumab 300 mg/2mL + 2 x 1 mL placebo s.c. at randomization, week 1 , 3, 4, thereafter 4-weekly until Week 48 intervention 3: Secukinumab 150 mg/1mL x 2 + 2 mL placebo s.c. at randomization, week 1 , 3, 4, thereafter 4-weekly until Week 48

Protocol document:
Prot_001.pdf: 
Global Clinical Development - General Medicine 
Secukinumab (AIN457) 
Clinical Trial Protocol [CAIN457A2323] / NCT02748863
A multicenter, randomized, double-blind,  
placebo-controlled, 52-weeks study to demonstrate 
the efficacy, safety and tolerability of subcutaneous 
secukinumAb injections with 2 mL pre-fiLLed syringes 
(300 mg) in adUlt subjects with moderate to seveRE 
plaque psoriasis – ALLURE 
Document type: 
Clinical Trial Protocol 
EUDRACT number: 
2015-005170-38 
Version number: 
00 (Original Protocol) 
Clinical trial phase: 
IIIb 
Release date: 
22-Feb-2016
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 03 (August 2015) 


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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 6 
List of figures ...................................................................................................................... 6 
List of abbreviations ............................................................................................................ 7 
Glossary of terms ................................................................................................................. 9 
Protocol summary .............................................................................................................. 10 
1 
Introduction ....................................................................................................................... 14 
1.1 
Background ............................................................................................................ 14 
1.2 
Purpose .................................................................................................................. 15 
2 
Study objectives and endpoints ......................................................................................... 15 
2.1 
Primary objective ................................................................................................... 15 
2.2 
Secondary objective(s) ........................................................................................... 16 
2.2.1 
Key secondary objectives ...................................................................... 16 
2.2.2 
Other secondary objectives ................................................................... 16 
 
 16 
3 
Investigational plan ........................................................................................................... 17 
3.1 
Study design........................................................................................................... 17 
3.2 
Rationale for study design ..................................................................................... 19 
3.3 
Rationale for dose/regimen, route of administration and duration of treatment .... 19 
3.4 
Rationale for choice of comparator ....................................................................... 20 
 
 20 
3.6 
Risks and benefits .................................................................................................. 20 
4 
Population .......................................................................................................................... 21 
4.1 
Inclusion criteria .................................................................................................... 22 
4.2 
Exclusion criteria ................................................................................................... 22 
5 
Treatment ........................................................................................................................... 24 
5.1 
Study treatment ...................................................................................................... 24 
5.1.1 
Investigational and control drugs .......................................................... 24 
5.1.2 
Additional treatment .............................................................................. 25 
5.2 
Treatment arms ...................................................................................................... 25 
5.3 
Treatment assignment and randomization ............................................................. 26 
5.4 
Treatment blinding ................................................................................................. 26 
5.5 
Treating the subject ................................................................................................ 27 
5.5.1 
Subject numbering ................................................................................ 27 
5.5.2 
Dispensing the study drug ..................................................................... 27 


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5.5.3 
Handling of study and additional treatment .......................................... 27 
5.5.4 
Instructions for prescribing and taking study treatment ........................ 28 
5.5.5 
Permitted dose adjustments and interruptions of study treatment ........ 29 
5.5.6 
Rescue medication ................................................................................ 29 
5.5.7 
Concomitant medication ....................................................................... 29 
5.5.8 
Prohibited medication ........................................................................... 29 
5.5.9 
Emergency breaking of assigned treatment code .................................. 30 
5.6 
Study completion and discontinuation ................................................................... 31 
5.6.1 
Study completion and post-study treatment .......................................... 31 
5.6.2 
Discontinuation of study treatment ....................................................... 31 
5.6.3 
Withdrawal of informed consent ........................................................... 33 
5.6.4 
Loss to follow-up .................................................................................. 33 
5.6.5 
Early study termination by the sponsor ................................................. 33 
6 
Visit schedule and assessments ......................................................................................... 34 
6.1 
Information to be collected on screening failures .................................................. 40 
6.2 
Subject demographics/other baseline characteristics ............................................. 40 
6.2.1 
Demographics ....................................................................................... 40 
6.2.2 
Psoriasis medical history/previous psoriasis therapies ......................... 40 
6.2.3 
Smoking history .................................................................................... 41 
6.2.4 
Co-morbidities – cardiovascular medical history ................................. 41 
6.2.5 
Relevant medical history/current medical conditions ........................... 41 
6.2.6 
Determination of the tuberculosis status ............................................... 41 
6.2.7 
Other baseline characteristics ................................................................ 43 
6.3 
Treatment exposure and compliance ..................................................................... 44 
6.4 
Efficacy .................................................................................................................. 44 
6.4.1 
Investigator Global Assessment (IGA mod 2011) ................................ 44 
6.4.2 
Assessment of total Body Surface Area (BSA) and Psoriasis Area 
Severity Index (PASI) ........................................................................... 45 
 
 47 
6.4.4 
Appropriateness of efficacy assessments .............................................. 47 
6.5 
Safety ..................................................................................................................... 47 
6.5.1 
Physical examination ............................................................................ 48 
6.5.2 
Vital signs.............................................................................................. 48 
6.5.3 
Height and weight ................................................................................. 48 
6.5.4 
Laboratory evaluations .......................................................................... 49 
6.5.5 
Electrocardiogram (ECG) ..................................................................... 50 


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6.5.6 
Pregnancy .............................................................................................. 51 
6.5.7 
Appropriateness of safety measurements .............................................. 51 
6.6 
Other assessments .................................................................................................. 51 
6.6.1 
Clinical Outcome Assessments (COAs) ............................................... 52 
 
 57 
6.6.3 
Pharmacokinetics .................................................................................. 57 
 
 58 
 
 58 
7 
Safety monitoring .............................................................................................................. 58 
7.1 
Adverse events ....................................................................................................... 58 
7.2 
Serious adverse events ........................................................................................... 60 
7.2.1 
Definition of SAE ................................................................................. 60 
7.2.2 
SAE reporting........................................................................................ 61 
7.3 
Liver safety monitoring ......................................................................................... 62 
7.4 
Renal safety monitoring ......................................................................................... 62 
7.5 
Reporting of study treatment errors including misuse/abuse ................................ 62 
7.6 
Pregnancy reporting ............................................................................................... 62 
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 ...................................................................................................................... 65 
9.1 
Analysis sets .......................................................................................................... 65 
9.2 
Subject demographics and other baseline characteristics ...................................... 65 
9.2.1 
Demographics and baseline characteristics ........................................... 65 
9.2.2 
Medical history ...................................................................................... 66 
9.3 
Treatments ............................................................................................................. 66 
9.3.1 
Study treatment ..................................................................................... 66 
9.3.2 
Prior and concomitant medication ........................................................ 66 
9.4 
Analysis of the primary variable(s) ....................................................................... 66 
9.4.1 
Co-primary Variable(s) ......................................................................... 67 
9.4.2 
Statistical model, hypothesis, and method of analysis .......................... 67 
9.4.3 
Handling of missing values/censoring/discontinuations ....................... 67 
9.4.4 
Sensitivity analyses ............................................................................... 68 


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9.5 
Analysis of key secondary variables ...................................................................... 68 
9.5.1 
Efficacy variables .................................................................................. 68 
9.6 
Analysis of other secondary and exploratory variables ......................................... 69 
9.6.1 
PASI 50, PASI 75, PASI 90, PASI 100 and IGA mod 2011 0 or 1 
response over time ................................................................................. 69 
9.6.2 
PASI score over time ............................................................................ 70 
9.6.3 
IGA mod 2011 score over time ............................................................. 70 
 
70 
 
 70 
9.6.6 
Safety variables ..................................................................................... 70 
9.6.7 
Health-related Quality of Life ............................................................... 71 
9.6.8 
Patient Reported Outcomes (PRO) ....................................................... 72 
 
 72 
9.6.10 
Pharmacokinetics .................................................................................. 72 
 
 72 
 
 73 
9.6.13 
Pharmacokinetics .................................................................................. 73 
 
 73 
9.8 
Sample size calculation .......................................................................................... 73 
9.8.1 
Primary endpoint (co-primary endpoint): ............................................. 73 
9.8.2 
Secondary endpoints(s): ........................................................................ 73 
10 Ethical considerations ........................................................................................................ 74 
10.1 
Regulatory and ethical compliance ........................................................................ 74 
10.2 
Informed consent procedures ................................................................................. 74 
10.3 
Responsibilities of the investigator and IRB/IEC .................................................. 74 
10.4 
Publication of study protocol and results............................................................... 74 
11 Protocol adherence ............................................................................................................ 75 
11.1 
Protocol amendments ............................................................................................. 75 
12 References ......................................................................................................................... 76 
13 Appendix 1: Clinically notable laboratory values and vital signs ..................................... 79 
14 Appendix 2: Blood collection log for pharmacokinetics 
 ................. 80 
15 Appendix 3: Scoring of the SIAQ ..................................................................................... 81 
16 Appendix 4: SIAQ Questionnaire ..................................................................................... 82 
17 Appendix 5: DLQI Questionnaire ..................................................................................... 84 
 85 
 


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List of tables 
Table 5-1 
Prohibited medication by period/epoch (for any indication) ................ 30 
Table 6-1 
Assessment schedule ............................................................................. 36 
Table 6-2 
The IGA mod 2011 rating scale ............................................................ 44 
Table 6-3 
The PASI scoring system ...................................................................... 46 
Table 6-4 
Self-injection assessment check list (2 mL syringe) ............................. 53 
Table 6-5 
Possible hazard assessment check list (2 mL syringe) .......................... 54 
Table 7-1 
Guidance for capturing the study treatment errors including 
misuse/abuse ......................................................................................... 62 
Table 14-1 
Blood collection log for pharmacokinetics ........................................... 80 
 
 80 
Table 15-1 
Scoring of domains from raw item scores............................................. 81 
 
List of figures 
Figure 3-1 
Figure 3-2 Study design ........................................................................ 17 
Figure 6-1 
Tuberculosis screening flowchart ......................................................... 43 
Figure 9-1 
Testing strategy ..................................................................................... 69 
                        


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List of abbreviations 
 
AE 
Adverse Event 
ALT/AST 
Alanine Aminotransferase/Aspartate Aminotransferase 
BDR 
Bioanalytical Data Report 
BSA 
Body Surface Area 
CFR 
US Code of Federal Regulations  
CHMP 
Committee for Medicinal Products for Human Use 
ClinRO 
Clinician Reported Outcomes 
COAs 
Clinical Outcome Assessments 
CPO 
Country Pharma Organization 
CRO 
Contract Research Organization 
CRP (hs-CRP) 
Human C-reactive protein 
CS 
Corticosteroids 
CSR 
Clinical Study Report 
CTCG 
Common Toxicity Grade Criteria 
DAR 
Dose Administration Record 
DLQI 
Dermatology Life Quality Index 
 
 
DS&E 
Drug Safety & Epidemiology 
EDC 
Electronic Data Capture 
ECG 
Electrocardiogram 
ECL 
Electrochemiluminescence 
eCRF 
Electronic Case Report Form 
ELISA 
Enzyme Linked Immunosorbent Assay 
EMA 
European Medicines Agency 
EU 
European Union 
FAS 
Full Analysis Set 
FDA 
United States Food and Drug Administration 
GCP 
Good Clinical Practice 
GGT 
Gamma–glutamyl transferase 
 
  
hCG 
Human chorionic gonadotropin 
HDL 
High-density lipoprotein 
HRQOL 
Health-related quality of life  
HIV 
Human Immunodeficiency virus 
H 
Home administrations 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
ID 
Identifier 
IFU 
Instructions For use 


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IGA mod 2011 
Investigator’s Global Assessment modified 2011 
IL 
Interleukin 
i.m. 
Intramuscular 
IN 
Investigator Notification 
ITT 
Intention-To-Treat-Analysis 
i.v. 
Intravenous 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee  
LDL 
Low Density Lipoprotein 
LLOQ 
Lower Limit of Quantification 
NIH 
National Institutes of Health 
IRT 
Interactive Response Technology 
NR/R 
Non-responders, responders 
MedDRA 
Medical dictionary for regulatory activities  
PASI 
Psoriasis Area and Severity Index 
PFS 
Pre-filled syringe 
PK 
Pharmacokinetics 
PPD 
Purified protein derivative 
PRO 
Patient Reported Outcome (paper or electronic) 
PsA 
Psoriatic Arthritis 
PUVA 
Photochemotherapy (e.g. psoralen + UVA treatment) 
QFT 
QuantiFERON TB-Gold test 
RPM 
Revolutions Per Minutes 
SAE 
Serious Adverse Event 
s.c. 
Subcutaneous 
SIAQ 
Self-Injection Assessment Questionnaire 
SGOT  
Serum Glutamic Oxaloacetic Transaminase  
SGPT  
Serum Glutamopyruvate Transferase  
SST 
Serum Separator Tubes 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TB 
Tuberculosis 
TCS 
Topical corticosteroid 
TD 
Study Treatment Discontinuation 
Th17 
T helper 17 cells 
TNFα 
Tumor necrosis factor alpha 
ULN 
Upper Limit of Normal 
UV 
Ultraviolet 
UVA 
Ultraviolet A, long wave 400 nm to 315 nm 
UVB 
Ultraviolet B, medium wave 315 nm to 280 nm 
WBC 
White blood cells/leukocytes 
WHO 
World Health Organization  
WoC 
Withdrawal of Consent 


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Glossary of terms 
 
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 
Dosage 
Dose of the study treatment given to the patient in a time unit (e.g. 
100 mg once a day, 75 mg twice a day) 
Enrollment 
Point/time of patient entry into the study at which informed consent 
must be obtained (e.g. prior to starting any of the procedures 
described in the protocol) 
Epoch 
 
A portion of the study which serves a specific purpose. Typical epochs 
are: Screening/Recruitment, Wash-out, Treatment, and Follow-up 
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” 
Medication pack number 
A unique identifier on the label of each investigational drug package 
Part  
A single component of a study which contains different objectives or 
populations within that single study. Common parts within a study are: 
a single dose part and a multiple dose part, or a part in 
patients/subjects with established disease and in those with newly-
diagnosed disease. 
Patient/subject ID  
A unique number assigned to each patient upon signing the informed 
consent  
Randomization number 
A unique identifier assigned to each randomized patient, 
corresponding to a specific treatment arm assignment 
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), 
placebo/comparator active drug run-ins or background therapy 
Study Treatment 
Discontinuation (TD) 
When the patient permanently stops taking study treatment prior to the 
defined study treatment completion date  
Variable 
A measured value or assessed response that is determined in specific 
assessments and used in data analysis to evaluate the drug being 
tested in the study 
Withdrawal of consent 
(WoC) 
Withdrawal of consent from the study is defined as when a patient 
does not want to participate in the study any longer, and does not want 
any further visits or assessments, and does not want any further study 
related contact, and does not allow analysis of already obtained 
biologic material 
 


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Protocol summary 
 
Protocol number 
CAIN457A2323 
Title 
A multicenter, randomized, double-blind, placebo-controlled, 52-weeks 
study to demonstrate the efficacy, safety and tolerability of subcutaneous 
secukinumAb injections with 2 mL pre-fiLLed syringes (300 mg) in adUlt 
subjects with moderate to seveRE plaque psoriasis - ALLURE  
Brief title 
 
Study of efficacy and safety of secukinumab 2 mL pre-filled syringe (300 
mg) in subjects with moderate to severe plaque psoriasis  
Sponsor and Clinical 
Phase 
Novartis/Phase IIIb 
Investigation type 
Drug  
Study type 
Interventional  
Purpose and rationale 
The primary purpose of this study is to assess efficacy, safety and 
tolerability of 2 mL pre-filled syringe of 300 mg secukinumab. Results of 
this study will support the registration of secukinumab 300 mg in 2 mL pre-
filled syringes.  
This 52-weeks, double-blind, randomized, parallel-group, and placebo-
controlled study is using the recommended dose of 300 mg secukinumab 
which has been approved in Japan, USA, EU, Switzerland and other 
countries for the treatment of moderate to severe psoriasis in adults. 
Primary Objective  
The primary objective is to demonstrate the efficacy of secukinumab 
300 mg when administered as 2 mL pre-filled syringes in subjects with 
plaque-type psoriasis with respect to both PASI 75 and IGA mod 2011 0 
or 1 response (co-primary endpoint) at Week 12, compared to placebo. 
Secondary Objectives 
Key Secondary Objectives 
• 
To demonstrate the efficacy of secukinumab 300 mg when 
administered as 2 mL pre-filled syringes in subjects with plaque-type 
psoriasis with respect to PASI 90 and PASI 100 at Week 12, compared 
to placebo. 
• 
To demonstrate the efficacy of secukinumab 300 mg when 
administered as two 1 mL pre-filled syringes in subjects with plaque-
type psoriasis with respect to PASI 100 at Week 12, compared to 
placebo. 
Other Secondary Objectives 
• 
To assess the efficacy of secukinumab 300 mg 2 mL pre-filled syringes 
on moderate to severe plaque-type psoriasis with respect to PASI 
score, IGA mod 2011 score, PASI 50 / 75 / 90 / 100 and IGA mod 2011 
0 or 1 response up to Week 12 compared to placebo, and over time 
up to Week 52.  
• 
To investigate the clinical safety and tolerability of secukinumab 
300 mg 2 mL pre-filled syringes as assessed by vital signs, clinical 
laboratory variables, and adverse events (AEs) monitoring, compared 
to placebo.  


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• 
To assess the subject usability (ability to follow instructions for use and 
potential use-related hazards) and satisfaction with the secukinumab 
2 mL pre-filled syringes utilizing a self-administered Self-Injection 
Assessment Questionnaire (SIAQ) and investigator / site staff 
observation of secukinumab 300 mg 2 mL pre-filled syringe 
administration.  
• 
To assess the effects of secukinumab 300 mg 2 mL pre-filled syringes 
with respect to Dermatology Life Quality Index (DLQI) 0 or 1 
achievement and DLQI changes at Week 12 compared to placebo, and 
over time up to Week 52. 
Study design 
This is a 52-weeks multicenter, randomized, double-blind, placebo-
controlled, parallel-group trial in approximately 210 subjects with moderate 
to severe plaque-type psoriasis.  
The study consists of 4 epochs: Screening (of at least 1 week and up to 4 
weeks), Treatment Epoch I (of 12 weeks), Treatment Epoch II (of 40 
weeks) and Follow-up. The treatment-free phase of 8-weeks should only 
be completed in case subjects discontinue early.  
Subjects will be randomized using a 1:1:1 ratio to the following groups: 
secukinumab 300 mg regimen group (2 mL), secukinumab 300 mg 
regimen group (1 mL) or to placebo. After administration of the Week 12 
dose, all subjects in the placebo group will continue the treatment based 
on their PASI 90 response status at Week 12. PASI 90 non-responders will 
receive in a 1:1 ratio either secukinumab 300 mg (2 mL) or secukinumab 
300 mg (1 mL). PASI 90 responders will continue to receive placebo. All 
treatment groups have additional matching placebos. 
Population 
Approximately 210 subjects with moderate to severe plaque psoriasis will 
be randomized in approximately 57 centers worldwide. Approximately 250 
subjects are expected to be screened to provide the number of randomized 
subjects. It is also expected to randomize approximately 20% of subjects 
who also suffer from psoriatic arthritis. 
Key Inclusion criteria 
Subjects eligible for inclusion in this study must 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 study consent according to local laws and 
regulations. 
2. Men or women of at least 18 years of age at the time of Screening. 
3. Chronic plaque-type psoriasis present for at least 6 months and 
diagnosed before Randomization. 
4. Moderate to severe psoriasis as defined at Randomization by: 
• 
PASI score of 12 or greater, and 
• 
IGA mod 2011 score of 3 or greater (based on a scale of 0 – 4), 
and 


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• 
Body Surface Area (BSA) affected by plaque-type psoriasis of 
10% or greater. 
5. Candidate for systemic therapy. This is defined as a subject having 
moderate to severe chronic plaque-type psoriasis that is inadequately 
controlled by 
• 
Topical treatment and/or 
• 
Phototherapy and/or  
• 
Previous systemic therapy 
Key Exclusion criteria 
1. Forms of psoriasis other than chronic plaque-type (e.g., pustular, 
erythrodermic and guttate psoriasis) at Screening or Randomization. 
2. Ongoing use of prohibited treatments. Washout periods detailed in the 
protocol have to be adhered to. Subjects not willing to limit UV light 
exposure (e.g., sunbathing and/or the use of tanning devices) during 
the course of the study will be considered not eligible for this study 
since UV light exposure is prohibited.   
Note: administration of live vaccines 6 weeks prior to Randomization 
or during the study period is also prohibited.  
3. Previous exposure to secukinumab (AIN457) or any other biologic 
drug directly targeting IL-17 or the IL-17 receptor. 
4. Use of other investigational drugs at the time of enrollment, or within 5 
half-lives of enrollment, or within 30 days until the expected 
pharmacodynamic effect has returned to baseline, whichever is longer; 
or longer if required by local regulations. 
5. 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. 
6. History of lymphoproliferative disease or any known malignancy or 
history of malignancy of any organ system treated or untreated within 
the past 5 years, regardless of whether there is evidence of local 
recurrence or metastases (except for Bowen’s disease, or basal cell 
carcinoma or actinic keratoses that have been treated with no 
evidence of recurrence in the past 12 weeks; carcinoma in situ of the 
cervix or non-invasive malignant colon polyps that have been 
removed).  
7. History of hypersensitivity to any of study drug constituent. 
Study treatment 
Novartis will supply the following study drugs with the same liquid 
formulation:  
Investigational Treatment: 
• 
Secukinumab 300 mg, provided in a 2 mL pre-filled syringe 
Control Treatment: 
• 
Secukinumab 300 mg, provided as two injections of 1 mL pre-filled 
syringe (each 1 mL syringe containing 150 mg secukinumab) 
• 
Secukinumab matching placebo, provided in a 1 mL or 2 mL pre-
filled syringe 
Efficacy assessments 
• 
Investigator’s Global Assessment (IGA mod 2011; scale from 0 – 
4) 


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• 
Psoriasis Area and Severity Index (PASI; score from 0 – 72) 
Key safety 
assessments 
• 
Evaluation of all AEs and SAEs  
• 
Physical examination 
• 
Vital signs 
• 
Height and weight 
• 
Laboratory evaluations (hematology, clinical chemistry) 
• 
 
• 
Pregnancy 
Other assessments 
• 
Usability and hazard assessment 
• 
SIAQ 
• 
DLQI 
• 
 
• 
Pharmacokinetic parameter 
Data analysis 
The hypotheses will be tested sequentially and are included in a 
hierarchical testing strategy. Type-I-errors are set to keep a family-wise 
type-I-error of 2.5% (one-sided): 
• 
H1: secukinumab 300 mg (2 mL s.c. injection) is not superior to 
placebo with respect to PASI 75 response at Week 12 
• 
H2: secukinumab 300 mg (2 mL s.c. injection) is not superior to 
placebo with respect to IGA mod 2011 0 or 1 response at Week 12 
• 
H3: secukinumab 300 mg (2 mL s.c. injection) is not superior to 
placebo with respect to PASI 90 response at Week 12 
• 
H4: secukinumab 300 mg (2 mL s.c. injection) is not superior to 
placebo with respect to PASI 100 response at Week 12 
• 
H5: secukinumab 300 mg (two 1 mL s.c. injections of 150 mg 
secukinumab) is not superior to placebo with respect to PASI 100 
response at Week 12 
The testing sequence will continue to H3 at α (one-sided) only if both H1 
and H2 have been rejected at α (one-sided). Similarly, the testing 
sequence will continue to H4 at α (one-sided) only if H3 testing has been 
rejected. In case, H4 has been rejected at α (one-sided), the 
corresponding alpha (α) will be passed to the next hypothesis 
corresponding to H5. 
Key words 
psoriasis, PASI, IGA mod 2011, secukinumab, pre-filled syringes 


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1 
Introduction 
1.1 
Background  
Psoriasis is a chronic relapsing disease of the skin characterized by variable clinical features. 
The lesions are classified as erythemato-squamous, which indicates that both the vasculature 
(erythema) and the epidermis (increased scale formation) are involved (Christophers et al 2003, 
Griffiths et al 2007).  
Plaque-type psoriasis (also called plaque or chronic plaque psoriasis) is the most frequent 
clinical presentation and therefore, also called psoriasis vulgaris. The erythematous plaques are 
well defined with sharp borders. The silvery grey scale on the surface of the lesions is easily 
removed. Sharply demarcated lesions can present on the extensor surfaces of the knees and 
elbows and on the trunk. Lesions are often symmetrically distributed. The size of the lesions is 
highly variable. In approximately one-third of patients, more than 10% of the body is covered, 
and this is termed moderate to severe psoriasis. Clinical disease can be assessed by a trained 
health-care practitioner, using the Psoriasis Area and Severity Index (PASI) score. This tool 
ranks severity and area of erythema (redness), induration (thickness), and desquamation (scale) 
of the plaques in different body sections, with 72 as the maximal score. PASI score of at least 
12 is required to classify for moderate to severe psoriasis.  
Treatment of moderate to severe psoriasis is based on phototherapy, systemic treatment (e.g. 
methotrexate, cyclosporine, acitretin, apremilast) and biologics. The introduction of tumor 
necrosis factor alpha (TNFα)-inhibitors such as etanercept, infliximab and adalimumab, 
increased treatment options for physicians. The primary indication for these biological products 
is the treatment of moderate to severe psoriasis not responding satisfactorily to conventional 
treatment such as phototherapy, methotrexate or acitretin. 
Extensive clinical experience with TNFα-inhibitors has been collected over the past 10 years 
and these agents are generally considered to be effective and relatively safe (Papp et al 2005). 
However, a substantial percentage of patients do not respond well to treatment with a TNFα-
inhibitor. This inadequate response may imply either a primary unsatisfactory response (e.g. 
not achieving a decrease in Psoriasis Area and Severity Index (PASI) score of at least 75% after 
adequate duration of treatment), an initially adequate response that is lost over time (secondary 
failure) or intolerance for the TNFα-inhibitor. The percentage of patients with an inadequate 
response to TNFα-inhibitors can be as high as 40-60% (Van Lümig et al 2010). 
The arrival of the anti-IL 12/23 class of biological drugs provided clinicians with another 
treatment option (Kerdel et al 2015). Ustekinumab has shown good clinical efficacy in a Phase 
III study (Papp et al 2008). PASI response rates were better than those of etanercept, and 
efficacy was generally maintained up to 3 years after initiation of treatment (Kimball et al 2012). 
More recently, a number of IL-17A and IL-17RA inhibitors are currently being investigated in 
Phase III studies for the treatment of a range of immune mediated inflammatory diseases (Puig 
2014). 
Secukinumab (AIN457) is a recombinant high-affinity fully human monoclonal anti-human 
IL-17A antibody of the immunoglobulin (Ig) G1/κ-class. Secukinumab binds to human IL-17A 
and neutralizes the bioactivity of this cytokine. IL-17A is the central cytokine of a newly defined 


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subset of inflammatory T cells, the Th17 cells which, in several animal models, are pivotal in 
multiple autoimmune and inflammatory processes. IL-17A is mainly produced by memory 
effector CD4+ and CD8+ T lymphocytes and is being recognized as one of the principal 
pro-inflammatory cytokines in immune mediated inflammatory diseases. Its neutralization is 
expected to treat the underlying pathophysiology of immune mediated disease, and as a 
consequence provide relief of (psoriatic) symptoms. Secukinumab has been shown to be 
superior to etanercept (Langley et al 2014) and superior to ustekinumab (Thaci et al 2015) in 
clearing skin of subject with moderate to severe psoriasis with a comparable safety profile. 
Secukinumab has a different mode of action to TNFα-inhibitors and IL-12/23 inhibitors as it 
targets a different interleukin (i.e. IL17A). Secukinumab (Cosentyx®) with a recommended 
dose of 300 mg was approved in 2014 in Japan, and 2015 in USA, EU, Switzerland, and other 
countries for the treatment of moderate to severe psoriasis in adults. Secukinumab is available 
as a powder for solution for injection, and as a solution of 150 mg in 1 mL for injection using 
pre-filled syringe or a pen/auto-injector. Currently two injections (each with 150 mg) for the 
recommended dose (300 mg) are required. In order to allow patients to receive only one 
injection for the delivery of secukinumab 300 mg instead of two injections of 150 mg, Novartis 
is currently developing the 2 mL syringe containing 300 mg of secukinumab.  
As of 25 June 2015, approximately 12,000 subjects have been enrolled in studies with 
secukinumab, of which 9,600 have received secukinumab at doses ranging from 0.1 mg/kg to 
30 mg/kg intravenously (i.v.), and from 25 mg to 300 mg subcutaneously (s.c.), given as single 
or multiple doses. As of 25 June 2015, there are 79 completed and multiple ongoing trials 
conducted with secukinumab in indications including psoriasis, psoriatic arthritis, ankylosing 
spondylitis, uveitis, multiple sclerosis, rheumatoid arthritis, rheumatic polymyalgia, type I 
diabetes mellitus, and asthma. These studies support a favorable safety profile without 
indication of any specific organ toxicity. The Investigator’s Brochure (IB) provides a more 
detailed review of the pre-clinical and clinical information on secukinumab. The aim of the 
present study is to assess the efficacy, safety, Pharmacokinetic (PK) parameters and local 
tolerability of a 2 mL pre-filled syringe of 300 mg secukinumab. 
1.2 
Purpose  
The primary purpose of this study is to assess efficacy, safety and tolerability of 2 mL pre-filled 
syringe of 300 mg secukinumab. Results of this study will support the registration of 
secukinumab 300 mg in 2 mL pre-filled syringes. 
2 
Study objectives and endpoints 
2.1 
Primary objective 
The primary objective is to demonstrate the efficacy of secukinumab 300 mg when 
administered as 2 mL pre-filled syringes in subjects with plaque-type psoriasis with respect to 
both PASI 75 and IGA mod 2011 0 or 1 response (co-primary endpoint) at Week 12, compared 
to placebo. 


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2.2 
Secondary objective(s) 
2.2.1 
Key secondary objectives 
• To demonstrate the efficacy of secukinumab 300 mg when administered as 2 mL pre-filled 
syringes in subjects with plaque-type psoriasis with respect to PASI 90 and PASI 100 at 
Week 12, compared to placebo. 
• To demonstrate the efficacy of secukinumab 300 mg when administered as two 1 mL pre-
filled syringes in subjects with plaque-type psoriasis with respect to PASI 100 at Week 12, 
compared to placebo. 
2.2.2 
Other secondary objectives 
• To assess the efficacy of secukinumab 300 mg 2 mL pre-filled syringes on moderate to 
severe plaque-type psoriasis with respect to PASI score, IGA mod 2011 score, PASI 50 / 
75 / 90 / 100 and IGA mod 2011 0 or 1 response up to Week 12 compared to placebo, and 
over time up to Week 52.  
• To investigate the clinical safety and tolerability of secukinumab 300 mg 2 mL pre-filled 
syringes as assessed by vital signs, clinical laboratory variables, and adverse events (AEs) 
monitoring, compared to placebo.  
• To assess the subject usability (ability to follow instructions for use and potential use-related 
hazards) and satisfaction with the secukinumab 2 mL pre-filled syringes utilizing a self-
administered Self-Injection Assessment Questionnaire (SIAQ) and investigator/site staff 
observation of secukinumab 300 mg 2 mL pre-filled syringe administration.  
• To assess the effects of secukinumab 300 mg 2 mL pre-filled syringes with respect to DLQI 
0 or 1 achievement and DLQI changes at Week 12 compared to placebo, and over time up 
to Week 52. 


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3 
Investigational plan 
3.1 
Study design 
This is a 52-week multicenter, randomized, double-blind, placebo-controlled, parallel-group 
trial in approximately 210 subjects with moderate to severe plaque-type psoriasis.  
The study consists of 4 epochs: Screening (of at least 1 week and up to 4 weeks), Treatment 
Epoch I (of 12 weeks), Treatment Epoch II (of 40 weeks) and Follow-up. The treatment-free 
phase of 8-week should only be completed in case of early discontinuations.  
Safety, efficacy and pharmacokinetic peak and trough level measurements of secukinumab will 
be performed according to the pre-defined visit schedule as described in Figure 3-1 and in Table 
6-1. 
Figure 3-1 
Figure 3-2 Study design  
 
 
NR = Week 12 PASI 90 Non-responder  
R = Week 12 PASI 90 Responder 
PFS = Pre-filled syringe 
Screening (Screening to Randomization) 
The screening of at least 1 week and up to 4 weeks will be used to assess eligibility of the 
subjects and to taper-off prohibited medication(s).  


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Treatment Epoch I (Randomization to Week 12 pre-dose) 
The Treatment Epoch I is defined as Randomization through Visit Week 12 (prior to Week 12 
dose). At the start of the Treatment Epoch I, eligible subjects will be randomized at a 1:1:1 ratio 
to one of three treatment groups: 
• Secukinumab 300 mg regimen group (2 mL syringe): one 2 mL secukinumab 300 mg 
plus two 1 mL matching placebo secukinumab s.c. injections once weekly for four weeks 
(at Randomization, Weeks 1, 2, and 3), followed by dosing every four weeks, starting at 
Week 4 up to Week 12.  
• Secukinumab 300 mg regimen group (1 mL syringe): two 1 mL secukinumab 150 mg 
plus one 2 mL matching placebo secukinumab s.c. injection once weekly for four weeks (at 
Randomization, Weeks 1, 2, and 3), followed by dosing every four weeks, starting at 
Week 4 up to Week 12.  
• Placebo group: placebo secukinumab (two 1 mL s.c. injections and one 2 mL injection per 
dose) once per week for four weeks (at Randomization, Visits Week 1, 2, and 3), followed 
by dosing every four weeks starting at Week 4 up to Week 12.  
For subjects who discontinue the study treatment prematurely for any reason before the End of 
the Treatment Epoch I, the End of Treatment Epoch I (EOTEI) Week 12 visit should be 
performed approximately four weeks after their last dose of study treatment (secukinumab or 
placebo). Thereafter, subjects should enter the treatment-free 8-week Follow-up Epoch.  
Subjects will be visiting the study site at Randomization and Visits Week 1, 2, 3, 4, 8 and 12. 
Treatment Epoch II (Week 12 post-dose to Week 52)  
The Treatment Epoch II is defined as Week 12 through Week 52.  
Prior to receiving the Week 12 dose, all subjects from the placebo group will be assigned to 
the following treatment groups based on their PASI 90 response status at Week 12. 
• PASI 90 non-responders from the placebo group will receive at a ratio 1:1 either one 
2 mL 300 mg secukinumab plus two 1 mL matching placebo OR two 1 mL of 150 mg 
secukinumab s.c plus one 2 mL matching placebo injections at Weeks 12, 13, 14, and 15, 
thereafter every four weeks starting at Week 16 and up to Week 48.  
• PASI 90 responders will receive their placebo injections at Weeks 12, 13, 14, 15, and 
then every four weeks starting at Week 16 up to Week 48.  
Subjects from the two active groups (who were on secukinumab since randomization) will 
receive placebo (one 2 mL and two 1 mL s.c. injections) at Weeks 13, 14 and 15 and continue 
with the treatment assigned at randomization every four weeks starting at Week 16 and up to 
Week 48. End of Treatment Epoch II (EOTEII) is at Week 52 and is also the end of the study. 
Home administrations (H) of study drug are scheduled at Weeks 20, 24, 32, 36, 44 and 48.  
End of Treatment Epoch II (EOTEII) is at week 52 and is also the formal end of the study. At 
this visit, the site should call IRT after performing the scheduled study assessments to record 
the completion by subject(s).  
 


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For subjects who discontinue study treatment prematurely for any reason before the end of the 
Treatment Epoch II, the End of Treatment Epoch II (EOTEII) Week 52 visit should be 
performed approximately four weeks after their last dose of study treatment (secukinumab or 
placebo). Thereafter, the subject should enter the treatment-free 8-week Follow-up Epoch.  
Follow-up Epoch (8 weeks) 
Only subjects who prematurely discontinue the treatment in Treatment Periods I or II for any 
reason will enter the treatment-free Follow-up Epoch to complete Visits F4 and F8 (as shown 
in Table 6-1). 
3.2 
Rationale for study design 
The intent of this study is to assess a 2 mL pre-filled syringe form for the administration of 
300 mg of secukinumab instead of two injections of 1 mL of 150 mg each, to psoriasis subjects 
that are treated with secukinumab at the recommended dose.  
This 52-weeks, double-blind, randomized, parallel-group, and placebo-controlled study is using 
the recommended dose of 300 mg secukinumab which has been approved in Japan, USA, EU, 
Switzerland and other countries for the treatment of moderate to severe psoriasis in adults.  
The study is in accordance with health authority guidelines and feedback on the clinical 
development program for the 2 mL pre-filled syringe, including the United States Food and 
Drug Administration (FDA) and EU agencies. The principle of a 2 mL s.c. injection is supported 
by a patient education document published by the National Institute of Health (NIH) that 
outlines the possibility to administer more than 1 mL of volume (NIH 2012). Based upon a 
recently conducted Novartis relative bioavailability study (CAIN457A2107) that assessed the 
300 mg dose with a 2 mL s.c. injection using different devices, the pharmacokinetic data with 
2 mL s.c. were similar to two marketed forms of 1 mL s.c. (pre-filled syringe and auto-
injector/pen) and safety data showed no issues with 2 mL s.c. injections, including local 
tolerability. Therefore, it is appropriate to initiate study CAIN457A2323. 
The primary endpoint of this study is at Week 12. This will allow for assessment of efficacy at 
a point in time for which efficacy data of current approved biologic therapies are available and 
which was the primary endpoint for the phase III studies with secukinumab in psoriasis, 
including those studies that introduced the liquid formulations (pre-filled syringe in 
CAIN457A2308, and auto-injector in CAIN457A2309; Blauvelt 2014, Paul 2015). 
Overall, this study will assess the efficacy, PK, safety 
 and 
tolerability of secukinumab and includes a human factor analysis (including usability [ability 
to follow instruction for use and potential use-related hazards] and satisfaction) of secukinumab 
in 2 mL pre-filled syringes when used both, short-term (up to 12 weeks) and long-term (up to 
52 weeks). This data will support the registration of secukinumab 300 mg in 2 mL pre-filled 
syringes. 
3.3 
Rationale for dose/regimen, route of administration and duration 
of treatment 
The placebo-controlled study design was chosen to demonstrate the efficacy of 300 mg 
secukinumab administered as 2 mL pre-filled syringe in adult subjects suffering from moderate 


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to severe psoriasis compared to placebo. The selected dose regimen for this study with an initial 
weekly schedule up to 4 weeks followed by an s.c administration of every four weeks up to 
Week 48 is in line with the posology and method of administration as described in the approved 
product labelling. The selected design with the two injections of secukinumab 1 mL pre-filled 
syringes will also allow the comparison of the PK and safety profile with the secukinumab 2 mL 
300 mg pre-filled syringe. 
3.4 
Rationale for choice of comparator 
Due to the nature of psoriasis and the outcome measures for the primary and the secondary 
endpoints used (PASI 50, 75, 90 and 100 and IGA mod 2011 0 or 1), a placebo arm is necessary 
for reliable results on efficacy and safety. Moreover, the inclusion of a placebo group is in 
accordance with health authority guidelines (CHMP Psoriasis Guideline 2004). The duration 
of 3 months treatment within the placebo group up to the primary endpoint at Week 12 is 
accepted for the indication of plaque-type psoriasis. Subjects from the placebo group that will 
not achieve PASI 90 after Week 12 will receive secukinumab.  
3.6 
Risks and benefits  
Secukinumab (Cosentyx®) 300 mg has been approved in moderate to severe psoriasis based on 
substantial clinical benefit and a favorable safety profile.  
In total 4,546 patients with moderate to severe plaque psoriasis were included in studies in the 
registration program. This included 3,430 patients treated with secukinumab in 10 phase II/III 
studies, 2,727 of whom were treated for at least 6 months and 2,029 of whom were treated for 
at least 48 weeks.  
Superiority of secukinumab to placebo was demonstrated for the co-primary efficacy criteria of 
PASI 75 and IGA mod 2011 0 or 1 at 12 weeks in all 4 pivotal placebo-controlled trials (> 62% 
for PASI 75 and > 48% for IGA mod 2011 0 or 1). Secukinumab was also found to be superior 
in efficacy compared to etanercept with a rapid onset of action in the etanercept and placebo-
controlled studies, CAIN457A2302 and CAIN457A2303 and superior to ustekinumab in 
CAIN457A2317. The safety data from the completed and ongoing studies including AE and 
SAE data, laboratory parameters and immunogenicity data demonstrate a favorable safety 
profile. Observed risks included infections in particular upper respiratory tract infections, 
neutropenia and hypersensitivity reactions that can be seen with administration of foreign 
proteins. Most of the infections were non-serious, mild to moderate in severity, clinically easily 


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manageable and did not lead to treatment discontinuation. Cases of neutropenia were 
uncommon, generally mild to moderate and transient and did not lead to treatment 
discontinuation, and only a few cases were temporally associated with non-serious infections. 
Subjects with pre-existing malignancies within the past 5 years are generally excluded from 
studies with secukinumab although there is no scientific basis to suggest that secukinumab 
would increase the risk for malignancies. Indeed, the majority of preclinical data, available in 
the literature, suggest that blocking IL-17A may actually prevent tumor growth. 
Fewer injection site reactions were reported with secukinumab 1 mL pre-filled syringe 
(containing 150 mg secukinumab), compared to etanercept, while the active treatment groups 
were higher vs. placebo. 
In the phase III studies CAIN457A2308 and CAIN457A2309, evaluating the safety and efficacy 
of secukinumab in liquid formulation in the 1 mL pre-filled syringe and 1 mL pre-filled 
pen/auto-injector, respectively, the data showed that the PASI response with both 150 mg and 
300 mg doses were superior to placebo (p < 0.0001). Comparing the efficacy and safety results 
across the phase III trials, the response rates in trials A2308 and A2309 were generally similar 
to those of the trials involving the lyophilized form (studies A2302 and A2303). It is expected 
that the 2 mL pre-filled syringe and 2 mL pre-filled pen/auto-injector are also comparable and 
have the same efficacy and safety profile as the liquid formulation remains the same. 
A recent relative bioavailability study (CAIN457A2107) to assess the pharmacokinetic 
parameters, safety and tolerability of a single administration of 300 mg secukinumab 
administered subcutaneously (s.c.) in healthy volunteers investigated several delivery systems 
to identify administration options for secukinumab. The data suggest that with a “simulated” 
2 mL pre-filled syringe (i.e. manual injection of 2 mL 300 mg in 10 seconds) i/ the 
pharmacokinetic profiles are similar to the 1 mL pre-filled syringe (with 2 injections), ii/ the 
tolerability (pain score) is acceptable, iii/ local reactions such as erythema, induration, 
hemorrhage, pruritus and leakage are minimum and finally, iv/ the safety profile is also similar 
to the 1 mL pre-filled syringe (with 2 x 1 mL s.c. injections). The 2 mL “simulated” form 
represented the best option from that study to provide the patients with a simple easy to use 
single-injection device for the treatment of psoriasis.  
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 with the 2 mL 300 mg pre-filled syringe, and therefore 
it is appropriate to initiate study CAIN457A2323 for registration purposes. 
4 
Population 
Approximately 210 subjects with moderate to severe plaque psoriasis will be randomized in 
approximately 57 centers worldwide. Approximately 250 subjects are expected to be screened 
to provide the number of randomized subjects. It is also expected to randomize approximately 
20% of subjects who also suffer from psoriatic arthritis. Drop-outs after randomization will not 
be replaced.  


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4.1 
Inclusion criteria 
Subjects eligible for inclusion in this study must 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 study consent according to local laws and 
regulations. 
2. Men or women of at least 18 years of age at the time of Screening. 
3. Chronic plaque-type psoriasis present for at least 6 months and diagnosed before 
Randomization. 
4. Moderate to severe psoriasis as defined at Randomization by: 
• PASI score of 12 or greater, and 
• IGA mod 2011 score of 3 or greater (based on a scale of 0 – 4), and 
• Body Surface Area (BSA) affected by plaque-type psoriasis of 10% or greater. 
5. Candidate for systemic therapy. This is defined as a subject having moderate to severe 
chronic plaque-type psoriasis that is inadequately controlled by 
• Topical treatment and/or 
• Phototherapy and/or 
• Previous systemic therapy 
4.2 
Exclusion criteria 
Subjects fulfilling any of the following criteria are not eligible for inclusion in this study. No 
additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible subjects. 
1. Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate 
psoriasis) at Screening or Randomization. 
2. Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium 
channel inhibitors or lithium) at Randomization. 
3. Ongoing use of prohibited treatments. Washout periods detailed in the protocol have to be 
adhered to (Table 5-1). Subjects not willing to limit UV light exposure (e.g., sunbathing 
and/or the use of tanning devices) during the course of the study will be considered not 
eligible for this study since UV light exposure is prohibited.   
Note: administration of live vaccines 6 weeks prior to Randomization or during the study 
period is also prohibited.  
4. Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting 
IL-17 or the IL-17 receptor. 
5. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of 
enrollment, or within 30 days until the expected pharmacodynamic effect has returned to 
baseline, whichever is longer; or longer if required by local regulations. 


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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. 
7. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective methods of contraception during the 
entire study or longer if required by locally approved prescribing information (e.g. in EU 
20 weeks).   
Effective contraception methods include: 
• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). 
Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods) and 
withdrawal are not acceptable methods of contraception. 
• Female sterilization (have had surgical bilateral oophorectomy (with or without 
hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking study 
treatment. In case of oophorectomy alone, only when the reproductive status of the woman 
has been confirmed by follow-up hormone level assessment. 
• Male sterilization (at least 6 months prior to Screening). The vasectomized male partner 
should be the sole partner for that subject. 
• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault 
caps). For UK: with spermicidal foam/gel/film/cream/vaginal suppository.  
• Use of oral, injected or implanted hormonal methods of contraception or other forms of 
hormonal contraception that have comparable efficacy (failure rate < 1%), e.g. hormone 
vaginal ring or transdermal hormone contraception or placement of an intrauterine device 
(IUD) or intrauterine system (IUS). 
• In case of use of oral contraception women should have been stable on the same pill for a 
minimum of 3 months before taking study treatment. 
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 have had surgical bilateral oophorectomy 
(with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of 
oophorectomy alone, only when the reproductive status of the woman has been confirmed 
by follow-up hormone level assessment is she considered not of child bearing potential.  
8. Active ongoing inflammatory diseases other than psoriasis and psoriatic arthritis (PsA) that 
might confound the evaluation of the benefit of secukinumab therapy.  Also, underlying 
conditions (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, 
neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the 
investigator significantly immunocompromises the subject and/or places the subject at 
unacceptable risk for receiving an immunomodulatory therapy. In addition, current severe 
progressive or uncontrolled diseases which renders the subject unsuitable for the trial or 
puts the subject at increased risk, including  any medical or psychiatric condition which, in 
the Investigator’s opinion, would preclude the participant from adhering to the protocol or 
completing the study per protocol. 
9.  Presence of : 


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• Significant medical problems, including but not limited to the following: uncontrolled 
hypertension (systolic ≥ 160 mmHg and/or diastolic ≥ 95 mmHg), congestive heart 
failure [New York Heart Association status of class III or IV]. 
• Serum creatinine level exceeding 2.0 mg/dl (176.8 µmol/L). 
• Total white blood cell (WBC) count < 2,500/µl, or platelets < 100,000/µl or 
neutrophils < 1,500/µl or hemoglobin < 8.5 g/dl at Screening.  
10.  Active systemic infections during the last two weeks (exception: common cold) prior to 
randomization or any infection that reoccurs on a regular basis. 
11.  History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis 
infection as defined by a positive QuantiFERON TB-Gold test (QFT) at Screening. 
Subjects with a positive or indeterminate QFT test may participate in the study if full 
tuberculosis work up (according to local practice/guidelines) was completed within 12 
weeks prior to randomization and establishes conclusively that the subject has no evidence 
of active tuberculosis. If presence of latent tuberculosis is established, then treatment must 
have been initiated and maintained according to local guidelines prior to randomization. 
12.  Past medical history record or current infection with HIV, hepatitis B or hepatitis C prior 
to Randomization. 
13.  History of lymphoproliferative disease or any known malignancy or history of malignancy 
of any organ system treated or untreated within the past 5 years, regardless of whether there 
is evidence of local recurrence or metastases (except for Bowen’s disease, or basal cell 
carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the 
past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant colon polyps that 
have been removed). 
14.  Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor 
tolerability or lack of access to veins).  
15.  History or evidence of ongoing alcohol or drug abuse, within the last six months before 
Randomization. 
16.  History of hypersensitivity to any of study drug constituent. 
5 
Treatment 
5.1 
 Study treatment 
5.1.1 
Investigational and control drugs 
Novartis will supply the following study drugs with the same liquid formulation:  
Investigational treatment: 
• Secukinumab 300 mg, provided in a 2 mL pre-filled syringe  
Control treatment: 
• Secukinumab 300 mg, provided as two injections of 1 mL pre-filled syringe (each 1 mL 
syringe containing 150 mg scekinumab)  


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• Secukinumab matching placebo, provided in a 1 mL or 2 mL pre-filled syringe 
Secukinumab and the secukinumab matching placebo will be labeled as “AIN457 
300 mg / Placebo” (2 mL) or “AIN457 150 mg / Placebo” (1 mL) to keep the blind. Subjects 
will be initially instructed about injections by site staff. They will receive 
explanations/instructions on how to self-inject the pre-filled syringe thereafter.  
The removable cap of the secukinumab pre-filled syringe 1mL form only contains a derivative 
of natural rubber latex (note: this is not applicable to the 2 mL syringe). Although no natural 
rubber latex is detected in the cap, the safe use of the secukinumab 1 mL pre-filled syringe in 
latex-sensitive individuals has not been studied. 
5.1.2 
Additional treatment 
No additional treatment beyond investigational drug and control drug are included in this trial. 
5.2 
Treatment arms 
Subjects will be assigned to one of the following 3 treatment arms with 70 subjects per arm. 
Subjects will self-administer all secukinumab and placebo doses at study sites or at home (Table 
6-1). There will always be three injections. 
Subjects will be randomized using a 1:1:1 ratio into one of the treatment groups: 
• Secukinumab 300 mg regimen group (2 mL): one 2 mL secukinumab 300 mg plus two 
1 mL matching placebo secukinumab s.c. injections once weekly for four weeks (at 
Randomization, Weeks 1, 2, and 3), followed by dosing every four weeks, starting at 
Week 4 up to Week 48. Subjects will receive three placebo injections at Weeks 13, 14 and 
15. 
• Secukinumab 300 mg regimen group (2 x 1 mL): two 1 mL secukinumab 150 mg plus 
one 2 mL matching placebo secukinumab s.c. injection once weekly for four weeks (at 
Randomization, Weeks 1, 2, and 3), followed by dosing every four weeks, starting at 
Week 4 up to Week 48. Subjects will receive three placebo injections at Weeks 13, 14 and 
15. 
• Placebo group: placebo secukinumab (two 1 mL s.c. injections and one 2 mL injection per 
dose) once per week for four weeks (at Randomization, Visits Week 1, 2, and 3), followed 
by dosing every four weeks starting at Week 4 up to Week 12.  
After administration of the Week 12 dose, all subjects in the placebo group will continue the 
treatment based on their PASI 90 response status at Week 12: 
• PASI 90 non-responders will receive 1:1 ratio either one 2 mL 300 mg secukinumab s.c. 
plus two 1 mL matching placebo OR two 1 mL 150 mg secukinumab s.c. injections plus 
one 2 mL matching placebo at Weeks 12, 13, 14, 15, and then every four weeks starting at 
Week 16 up to Week 48.  
• PASI 90 responders will continue on placebo (one 2 mL plus two 1 mL s.c. injections) and 
will receive their placebo injections at Weeks 12, 13, 14, 15, and then every four weeks 
starting at Week 16 up to Week 48.  


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5.3 
Treatment assignment and randomization  
At Baseline/Randomization visit, all eligible subjects will be randomized via Interactive 
Response Technology (IRT) to one of the treatment arms. The investigator or his/her delegate 
will contact the IRT after confirming that the subject fulfills all the inclusion/exclusion criteria. 
The IRT will assign a randomization number to the subject, which will be used to link the 
subject to a treatment arm and will specify a unique medication number for the package of study 
drug to be dispensed to the subject. The randomization number will not be communicated to 
the caller.  
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from subjects and investigator staff. A subject 
randomization list will be produced by the IRT using a validated system that automates the 
random assignment of subject numbers to randomization numbers. These randomization 
numbers are linked to the different treatment arms, which in turn are linked to medication 
numbers. 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).  
If a subject discontinues before Randomization, the IRT should be notified within five days and 
the reason for not being randomized will be entered in the Screening Epoch Disposition 
electronic Case Report Form (eCRF).  
Randomization will not be stratified. 
The randomization scheme for subjects will be reviewed and approved by a member of the 
Randomization Group.  
5.4 
Treatment blinding  
Subjects, investigators/site personnel and Novartis clinical team reviewing data will remain 
blind to the identity of the treatment from the time of randomization, using the following 
methods: (1) randomization data 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 treatment that are all identical in packaging, 
labeling, appearance, and schedule of administration. 
Unblinding will only occur in the case of subject emergencies (Section 5.5.9), at the time of the 
endpoint analysis (Section 3.5) as described below. 
The blind will be kept until the final/end of study database lock. 
The randomization codes associated with subjects from whom PK samples are taken will be 
disclosed to PK analysts who will keep PK results confidential until database lock. 
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. Study treatment must be discontinued after emergency 
unblinding (Section 5.5.9).  


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5.5 
Treating the subject  
5.5.1 
Subject numbering 
Each subject 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 
subject, the Subject Number will not be re-used.  
Upon signing the Informed Consent Form (ICF), the subject is assigned the next sequential 
number by the investigator. The investigator or his/her staff will contact the IRT and provide 
the requested identifying information for the subject to register them into the IRT. The site must 
select the eCRF book with a matching Subject Number from the EDC system to enter data.  
5.5.2 
Dispensing the study drug 
Each study site will be supplied with study drug in packaging of identical appearance. 
The study drug packaging has a 2-part label. A unique medication number is printed on each 
part of this label which corresponds to one of the 2 treatment arms.  Investigator staff will 
identify the study drug package(s) to dispense to the subject by contacting the IRT and obtaining 
the medication number(s). Immediately before dispensing the package to the subject, 
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.  
5.5.3 
Handling of study and additional treatment 
5.5.3.1 
Handling of study treatment 
Study 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 study treatment must be stored according to the instructions 
specified on the labels. Clinical supplies are to be dispensed only in accordance with the 
protocol. Technical complaints are to be reported to the respective Novartis Country Pharma 
Organization (CPO) Quality Assurance. 
Medication labels will be in the local language and comply with the legal requirements of each 
country. They will include storage conditions for the study treatment but no information about 
the subject except for the medication number. 
The investigator must maintain an accurate record of the shipment and dispensing of study 
treatment in a drug accountability log. Monitoring of drug accountability will be performed by 
monitors during site visits or remotely 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 study treatment, packaging, drug labels, and a copy of the completed drug 
accountability log as instructed.  
5.5.3.2 
Handling of additional treatment 
Not applicable. 


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5.5.4 
Instructions for prescribing and taking study treatment 
The first study treatment administration will occur at the Randomization Visit after the 
inclusion/exclusion criteria have been confirmed and all study scheduled assessments have been 
performed (except the SIAQ POST module to be completed 20-40 minutes after dosing of all 
three injections). All other study assessments, including blood withdrawal and completion of 
Patient Reported Outcomes (PROs), i.e. DLQI, 
 except the SIAQ POST module as 
applicable, should be completed prior to the self- injection of study treatment. The flow of work 
and the consecutive steps of assessments including Clinical Outcome Assessments (COA) are 
given in Section 6. 
All doses of study treatment (secukinumab and/or placebo) will be self-administered by the 
subject either at the study site after the study assessments for the visits have been completed or 
at home.  
The first use at Randomization and the Week 1 assessments of the self-injection will take place 
in the context of an observed assessment under the supervision of one site staff member. Each 
assessment will be conducted on a 1:1 basis. At the Randomization Visit the subjects will be 
instructed through the site staff by walking them through the Instructions For Use (IFU) on how 
to self-inject via the pre-filled syringe (IFU brochure containing detailed information about self-
administration of study treatment should be provided to each subject at the beginning of the 
study). After providing detailed explanations/instructions, subjects will then be asked to raise 
any questions. Thereafter, they will proceed with self-injection. At Week 1 subjects will be 
asked to refer to the IFU and to proceed with self-injection of the actual study drug (i.e. without 
a detailed explanation/instruction on handling the syringe). During the first two self-injections 
at the respective visits (Randomization and Week 1) site staff will observe and complete the 
self-injection assessment checklist for the 2 mL syringe (Table 6-4) at the first of the two 
injections at each visit. The possible hazard assessment check list (Table 6-5) will be assessed 
at each of the applicable visits. 
Home administrations (H) should be done at pre-defined visits (Table 6-1). Home 
administration can be performed by subject or trained caregiver.  If the subject or caregiver is 
not able/confident to perform home administration, the subject will be allowed to return to the 
site for administration of the medication. However, during those visits no additional 
assessments will be required.  
During home administrations subjects are expected to contact the investigator/site staff in case 
they are experiencing any AE/SAEs or have any concerns. 
Administration 
The study treatment solution must be injected in non-affected areas of the skin. 
Administration of study treatment may vary on the body regions, i.e. changing the injection site 
whilst separating the 2 mL syringe and the two 1 mL syringes.  
Pre-filled syringes should be kept at 2 to 8°C (36°F and 46°F),  never be frozen,  and should 
be protected from light. Prior to administration, the boxes containing the pre-filled syringes 
should be allowed to adapt to room temperature unopened for about 20 minutes before 


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administration. Used syringes should be disposed immediately after  use  in  a  sharps  container 
or according to the regulatory needs of the respective countries. 
5.5.5 
Permitted dose adjustments and interruptions of study treatment  
Investigational or other treatment dose adjustments and/or interruptions are not permitted. 
5.5.6 
Rescue medication 
Use of rescue medication is not permitted in this study.  
5.5.7 
Concomitant medication  
The investigator must instruct the subject to notify the study site about any new medications 
he/she takes after the subject was enrolled into the study. All medications, procedures and 
significant non-drug therapies (including physical therapy and blood transfusions) administered 
after the subject was enrolled into the study must be recorded.  
Any treatment known to worsen psoriasis (e.g. beta-blockers, calcium channel blockers, 
lithium) should be stable at least 4 weeks before randomization. 
5.5.8 
Prohibited medication 
Use of any treatments displayed in Table 5-1 that could confound the efficacy of the 
investigational drug is NOT allowed during the study for any indication.  After Screening, the 
use of concomitant medication for psoriasis in all body regions is restricted to bland emollients 
(not supplied by Novartis) and other non-medicated interventions. Use of bland emollients must 
be recorded on the Concomitant Medications eCRF and should be avoided during the 12 hours 
preceding a scheduled visit. Use of any other non-medicated interventions should be recorded 
in the eCRF.  
A mild to moderate potency topical corticosteroid (TCS) will be allowed for the treatment of 
the face, scalp, and anogenital area during the Screening Epoch.  These TCS should be stopped 
at least the day before the Randomization Visit.  
The investigator should instruct the subject to notify the study site about any/all new/additional 
treatments after starting the study drug administration. Prior to starting the study, all prohibited 
treatments should be washed out as shown in Table 5-1 below. At the discretion of the 
investigator,  if any use of a prohibited treatment presents  an undue  safety  risk  for  the  subject,  
the  study treatment  should  be discontinued. If a live vaccination has to be administered, the 
study treatment should be discontinued. 


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Table 5-1 
Prohibited medication by period/epoch (for any indication) 
Prohibited medicationa, b 
Washout period  
(before randomization) 
Alefacept, briakinumab, efalizumab, ustekinumab 
24 weeks   
Biological immunomodulating agents other than above  
(e.g., adalimumab, etanercept, infliximab) 
12 weeks  
Other systemic immunomodulating treatmentsc 
(e.g. Methotrexate, cyclosporine A, corticosteroidsc, 
cyclophosphamide)  
4 weeks  
Other systemic psoriasis treatmentsd (e.g. retinoids, fumarates, 
apremilast) 
4 weeks 
Photochemotherapy (e.g., PUVA)  
4 weeks  
Phototherapy (e.g., UVA, UVB)  
2 weeks  
Topical treatment that is likely to impact signs and symptoms of 
psoriasis (e.g. potent corticosteroids [CS], vitamin D analogues, 
pimecrolimus, tacrolimus, retinoids, salicylvaseline, salicylic 
acid, lactic acid, tar, urea, α-hydroxy or fruit acids)e, f 
2 weeks  
Live virus vaccinations*** 
6 weeks 
Any investigational treatment (including IL23p19) or participation 
in any interventional trial 
 
4 weeks or 5 half-lives 
(whichever is longer)  
a If a prohibited treatment of psoriasis was used during the study, the subject should discontinue use of the prohibited treatment if 
he/she wishes to continue in the study.  
b 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. 
c Oral, i.v., i.m., s.c., intra-articular, peri-articular. Exception: inhalative corticosteroids (CS) with only a topical effect (e.g., to treat 
asthma) are not considered “systemic immunomodulating treatments” and are therefore acceptable as co-medication.  
d There is no restriction on the use of anti-histamines and on the use of corticosteroids in the eye, nose or the ear 
e Mild to moderate topical corticosteroids (TCS) are allowed only during the Screening Epoch if used only on the face, scalp 
and/or anogenital area and should be stopped the day before the Randomization visit. 
f Topical corticosteroids (mild to moderate) and other topical treatments will be allowed during Treatment Epoch II ONLY if (all 
must apply): 
- 
medication was started after the Week 12 visit was completed; 
- 
medication was used for 14 consecutive calendar days or less; 
- 
medication was used for an indication other than psoriasis and not on the area affected with psoriasis. 
*** Inactivated virus vaccinations are allowed 
 
Exposure to light 
Exposure to ultraviolet (UV) light (including sunbathing and/or use of UV tanning devices) 
should be limited to avoid possible effect on psoriasis. 
5.5.9 
Emergency breaking of assigned treatment code 
Emergency code breaks must only be undertaken when it is required to in order to treat the 
subject safely. Most often, study treatment discontinuation and knowledge of the possible 
treatment assignments are sufficient to treat a study subject who presents with an emergency 


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condition. Emergency treatment code breaks are performed using the IRT. When the 
investigator contacts the system to break a treatment code for a subject, he/she must provide the 
requested subject identifying information and confirm the necessity to break the treatment code 
for the subject. The investigator will then receive details of the investigational drug treatment 
for the specified subject and an e-mail with an onscreen display of the medication confirming 
this information. The system will automatically inform the Novartis monitor for the site and the 
Study Team that the code has been broken. 
It is the investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT at any time in case of emergency. The investigator will provide: 
• Protocol number 
• Study drug name (if available and applicable) 
• Subject number 
In addition, oral and written information to the subject must be provided on how to contact 
his/her backup in cases of emergency, or when he/she is unavailable, to ensure that un-blinding 
can be performed at any time.  
Study treatment must be discontinued after emergency unblinding. 
5.6 
Study completion and discontinuation  
5.6.1 
Study completion and post-study treatment 
A subject will be considered to have completed the study when the subject has completed the 
last visit planned in the protocol (Visit Week 52 or Visit F8). 
The investigator must provide follow-up medical care for all subjects who are pre-maturely 
withdrawn from the study, or must refer them for appropriate ongoing care. 
5.6.2 
Discontinuation of study treatment  
Discontinuation of study treatment for a subject occurs when study drug is stopped earlier 
than  the  protocol  planned  duration,  and  can  be  initiated  by  either  the  subject  or  the 
investigator. 
Subjects may voluntarily discontinue study treatment for any reason at any time. 
The investigator must discontinue study treatment for a given subject if, on balance, he/she 
believes that continuation would negatively impact the risk/benefit of trial participation. 
Study treatment must be discontinued under the following circumstances: 
• Subject wish 
• Withdrawal of consent 
• Emergence of the following AEs: AEs that in the judgment of the investigator/qualified 
site staff, taking into account the subject’s overall status prevent the subject from 
continuing study treatment. 


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• Any laboratory abnormalities that in the judgment of the investigator/qualified site staff, 
taking into consideration the subject’s overall status, prevent the subject from continuing 
study treatment. 
• Pregnancy (Section 6.5.6 and Section 7.6) 
• Ongoing use of prohibited treatment as shown in Table 5-1 
• Any situation in which study participation might result in a safety risk to the subject 
• Emergency unblinding 
If discontinuation of study treatment occurs for any reason, the subject should NOT be 
considered   withdrawn   from   the   study.   The   subject   should   return   to   the   site  after 
discontinuation of study drug, for an End of Treatment visit and Follow-up visits (F4 and F8). 
Assessments detailed in the “End of Treatment visit” and Follow-up visits (F4 and F8) in 
Table 6-1 should be completed and recorded in the eCRF. The investigator must determine the 
primary reason for the subject’s premature discontinuation of study treatment and record this 
information on the eCRF. 
At the time of the study treatment discontinuation visit, if it has been approximately 4 weeks 
post last dose of study treatment then the assessments described in EOTEI OR EOTEII should 
be completed at this visit. 
If it has not been approximately 4 weeks post last dose of study treatment at the time of the 
study treatment discontinuation visit, then the subject should be scheduled to return 4 weeks 
post last dose for their EOTEI assessments OR EOTEII assessments. 
The investigator/qualified site staff must contact the IRT when the subject completes the EOT 
Visit Week 12/EOTEI OR Week 52/EOTEII assessments to register the subject’s early 
completion of the study due to study treatment discontinuation.  
Further, the subject should also return for the final Follow-up visits, F4 (8 weeks after last study 
treatment) and F8 (12 weeks after last study treatment) as shown in Table 6-1. 
After study treatment discontinuation, at a minimum, the following data should be collected at 
site visits or via telephone visits: 
• New/concomitant treatments 
• Adverse events/serious adverse events 
If the subject cannot or is unwilling to attend any visit(s), the site staff should maintain regular 
telephone contact with the subject, or with a person pre-designated by the subject. This 
telephone contact should preferably be done according to the study visit schedule. 
The investigator must also contact the IRT to register the subject’s discontinuation from study 
treatment. 
If study drug discontinuation occurs because treatment code has been broken, please refer to 
Section 5.5.9. 
5.6.2.1 
Discontinuation from a treatment-free period 
If premature withdrawal occurs for any reason in the treatment-free period (within the four 
weeks after last dose or in the 8-week Follow-up Epoch), the investigator must make every 


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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 eCRF (i.e. F8). 
In Section 6 assessments for subjects who discontinue from the Follow-up Epoch are shown.  
5.6.3 
Withdrawal of informed consent 
Subjects may voluntarily withdraw consent to participate in the study for any reason at any 
time. Withdrawal of consent from the study is defined as when a subject: 
• Does not want to participate in the study anymore 
and 
• Does not want any further visits or assessments 
and 
• Does not want any further study related contacts 
and 
• Does not allow analysis of already obtained biologic material  
In this situation, the investigator must make every effort (e.g. telephone, e-mail, letter) to 
determine the primary reason for the subject’s decision to withdraw his/her consent and record 
this information.  
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing.  
Further attempts to contact the subject are not allowed unless safety findings require 
communicating or follow-up. 
All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the subject’s study withdrawal should be made as detailed in  
Table 6-1. 
5.6.4 
Loss to follow-up  
For subjects whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or 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. A subject cannot be considered as lost to follow-up until the time 
point of his/her scheduled end of study visit has passed. 
5.6.5 
Early study termination by the sponsor 
The study can be terminated by Novartis at any time for any reason. This may include reasons 
related to the benefit risk assessment of participating in the study, practical reasons, or for 
regulatory or medical reasons (including slow enrollment). Should this be necessary, the subject 
must be seen as soon as possible and treated as a prematurely withdrawn subject. 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 subject’s interests. The investigator will 


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be responsible for informing the Institutional Review Board/Independent Ethics Committee 
(IRBs/IECs) of the early termination of the trial. 
6 
Visit schedule and assessments 
Table 6-1 lists assessments that are recorded in the clinical database. Assessments that are 
source documentation only will not be entered into the eCRF. Data reflecting to which 
inclusion/exclusion criteria are not met are captured on the Inclusion/Exclusion eCRF.  
Subjects should be seen for all visits on the designated day or as closely as possible to the original 
planned visit schedule (Table 6-1). Every effort should be made to respect the timeframe for all 
visits and particularly when PK samples are collected.  
If for any reason the subject is a screen failure, the subject may be re-screened. There is no 
restriction on the number of times a potential subject may be re-screened or on how much time 
must pass from the date of screen failure and the date of re-screening. 
If a subject re-screens for the study, then the subject must sign a new ICF and be issued a new 
subject number prior to any screening assessment being conducted for the subject under the 
new screening subject number. For all subjects, the investigator/qualified site staff will record 
if the subject was re-screened on the re-screening eCRF and any applicable screening numbers 
the subject was issued prior to the current screening number. The date of the new informed 
consent signature must be entered on the Informed Consent eCRF to correspond to the new 
screening subject number. For re-screening, all screening assessments must be performed per 
protocol, except for the tuberculosis (TB) work up and chest x-ray, if applicable, if performed 
not more than 12 weeks before randomization. 
For subjects who discontinue study treatment prematurely before the end of the treatment epoch 
for any reason other than withdrawal of informed consent or loss to follow-up procedures 
as described in Section 5.6 should be followed. 
During Treatment Epochs I and II, 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. The assessment(s) performed at an unscheduled visit are at the 
investigator’s discretion.  
Order of assessments: 
Guidance for the order of assessments as shown in Table 6-1 is as follows (may vary depending 
on different type of visits): 
Subjects 
• Subjects should usually complete the subject-reported outcome (PROs/ePROs) assessments 
(i.e. DLQI 
) prior to any investigator assessments.  
Investigator / Qualified Site Staff 
1. IGA mod 2011 
2. PASI 
3. Other procedures 


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• All remaining study visit procedures (e.g. laboratory and PK sample collection, vital 
signs measurements) must be completed prior to study treatment administration. 
• Enter PASI and IGA mod 2011 assessments into eCRFs BEFORE contacting IRT at 
Randomization Visit and EOTEI Visit Week 12. 
• Contact IRT to register the subject visit. 
• Prepare  the  corresponding  study  medication  packs  and  allow  to  adapt to room 
temperature for about 20 minutes before administration (dispense for home 
administrations, as required). 
• Provide guidance to subjects for self-administration prior to the first treatment 
administration (Section 5.5.4) at Randomization; from Visit Week 1 until End of 
Treatment Epoch II subjects should refer to the Instructions For Use (IFU) and proceed 
with self-administrations either at the site or they receive instructions for sub-sequent 
home administrations (H).  
• SIAQ PRE module should be performed once at Randomization  
• Subject self-administration assessment 
• Pre-filled syringe usability and hazard assessment should be done by site personnel, at 
Randomization Visit and at Visit Week 1  
• SIAQ POST module, as shown in Table 6-1  


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Table 6-1 
Assessment schedule 
 
 
Epoch 
Scr 
Treatment Epoch I 
Treatment Epoch II 
FU 
EPOCHc 
U 
Week (Relative to 
Randomization) 
≤ - 4 
Ri 
1 
2 
3 
4 
8 
12a 
EOTEI 
13 
 
14 
 
15 
 
16  
 
20 
H 
24 
H 
28 
 
32 
H 
36 
H 
40 
 
44 
H 
48 
H 
52b 
EOTEII F4 
F8b 
Day 
≤ - 28 to  
≥ - 7 
R 
8 
15 
22 
29 
57 
85 
92 
99 106 113 141 169 197 225 253 281 309 337 
365 
393 
421 
Obtain informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteriad 
S 
S 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Smoking history  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Psoriasis medical history/ 
Previous psoriasis therapies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiovascular medical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history and prior 
medications 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
X 
Physical Examinationd 
S 
S 
 
 
 
 
 
S 
 
 
 
S 
 
 
S 
 
 
S 
 
 
S 
S 
S 
S 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
Vital signs 
X 
X 
 
 
 
X 
X 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
X 
Lab analysis: safety panele 
X 
X 
 
 
 
X 
X 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
X 
X 
Fasting labs: glucose, lipid 
panel, high sensitivity CRPe  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urinalysis (local) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Epoch 
Scr 
Treatment Epoch I 
Treatment Epoch II 
FU 
EPOCHc 
U 
Week (Relative to 
Randomization) 
≤ -4 
Ri 1 
2 
3 
4 
8 
12a 
EOTEI 
13 
 
14 
 
15 
 
16  
 
20 
H 
24 
H 
28 
 
32 
H 
36 
H 
40 
 
44 
H 
48 
H 
52b 
EOTEII F4 
F8b 
Day 
≤ -28 to 
≥ -7 
R 
8 
15 
22 
29 
57 
85 
92 
99 106 113 141 169 197 225 253 281 309 337 
365 
393 
421 
QuantiFERON® TB-Gold 
In-Tube teste 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy teste  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
(local)f 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
ECG (standard 12 lead) 
S 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sample for PK g,k,l,e 
 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
 
 
X 
 
 
 
 
 
X 
 
 
X 
PASI 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
X 
BSA 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IGA mod 2011 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
X 
DLQI 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
X 
SIAQh 
 
X 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
X 
Usability and hazard 
assessment 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event  
(SAE/AE)  
assessmentj  
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
X 


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Epoch 
Scr 
Treatment Epoch I 
Treatment Epoch II 
FU 
EPOCHc 
U 
Week (Relative to 
Randomization) 
≤ - 4 
Ri 1 
2 
3 
4 
8 
12a 
EOTEI 
13 
 
14 
 
15 
 
16  
 
20 
H 
24 
H 
28 
 
32 
H 
36 
H 
40 
 
44 
H 
48 
H 
52b 
EOTEII F4 
F8b 
Day 
≤ - 28 to 
≥ - 7 
R 
8 
15 
22 
29 
57 
85 
92 
99 106 113 141 169 197 225 253 281 309 337 
365 
393 
421 
Administration of study 
treatment at site 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
Home administration  
(H)m 
 
 
 
 
 
 
 
 
 
 
 
 
H 
H 
 
H 
H 
 
H 
H 
 
 
 
 
Randomization and 
supply order by IRTa  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
 
 
 
X 
Screening period eCRF 
completion 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EOTEI eCRF completion  
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EOTEII eCRF completion  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
EOF eCRF completion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
AE = adverse event, BSA = Body Surface Area, CRP = high sensitivity C-reactive protein, DLQI =  Dermatology Life Quality Index, eCRF = electronic case report form,  
EOF = End of Follow-up, EOTEI = End of Treatment Epoch I, EOTEII = End of Treatment Epoch II,  FU = Follow up, 
 
 H = home administration (self-injection or trained caregiver), IGA mod 2011 =  Investigator’s Global Assessment modified 2011, 
, 
IRT = Interactive Response Technology, PASI = Psoriasis Area and Severity Index, PK = Pharmacokinetics, R = randomization, SAE = serious adverse event, Scr = 
screening,  SIAQ = Self-Injection Questionnaire, S = assessment only recorded in source documentation,  U = unscheduled visits - assessments performed at 
unscheduled visits are at investigator’s discretion;  X = assessment entered or transferred into the clinical data base  
a During Visit Week 12, subjects will have their last assessments performed for the Treatment Epoch I prior to the dose at this visit.  
b, c At Visit Week 52, subjects will have their last assessments performed for the Treatment Epoch II which is also the formal end of the study. Visit Week 12 (EOTEI) 
must be completed for treatment discontinuations from the Treatment Epoch I and Visit Week 52 (EOTEII) must be completed for treatment discontinuations from 
Treatment Epoch II; all discontinuations should then continue with their corresponding Follow-up Visits F4 and F8. A Follow-up Epoch is not needed for 
subjects who complete the study up to Visit Week 52; completers have their last visit at Week 52.  
d These assessments are source documentation only and will not be entered into the eCRF. However, data regarding to which inclusion/exclusion criteria are not met are 
captured on the Inclusion/Exclusion Screen eCRF. 
e Samples will be shipped to and analyzed by the central laboratory 


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f 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. A urine pregnancy test is not 
required for a woman who is sterile or who is not of childbearing potential.  
g Samples will be shipped by the sites and stored by the central laboratory. A shipment to reference laboratories for analysis will be done by the central laboratory. 
Detailed sampling intervals for PK 
 are shown in Appendix 2 in Table 14-1 and Table 14-2. 
h SIAQ PRE module only at Randomization, SIAQ POST module for all SIAQ time points  
i The PASI Score and IGA mod 2011 eCRFs must be completed prior to contacting IRT for randomization. At Randomization Visit, the investigator must confirm subject 
meets IGA mod 2011, PASI and BSA eligibility per these eCRFs before randomizing the subject. At EOTEI Visit Week 12, the site must have the PASI 90, see a) and b) 
responder status from the PASI Score eCRF available for entry into IRT. 
j Adverse events that my occur at home administrations as well as concomitant medication should be collected by the investigator and reported in the eCRF 
k An unscheduled 
 PK sample is collected only to replace 
 PK sample not taken at a regular scheduled visit. In case an unscheduled 
 sample is 
taken, there should always be a matching unscheduled PK sample taken at the same time point (both pre-dose). 
l Blood withdrawals for PK sampling: pre-dose samples at Randomization, Weeks 4, 12, 13, 14, 15, 16, 28; one last pre-dose blood withdrawal for PK is scheduled at 
Week 52. An additional pre-dose sample should be withdrawn in case of early discontinuations at Visit F8 or if an unscheduled visit (U) is conducted Appendix 2 in 
Table 14-1.  
m Home administrations can be performed by subject or caregiver.  If the subject or caregiver is not able/confident to perform home administration, the subject will be 
allowed to return to the site for administration of the medication.  


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6.1 
Information to be collected on screening failures 
Subjects who sign the Informed Consent Form (ICF) and discontinue prior to randomization at 
the Randomization Visit are considered screening failures. 
If a subject discontinues before entering the double-blind Treatment Epoch I, the IRT must be 
notified within five days and the reason for not being randomized will be entered in the 
Screening Epoch Disposition electronic Case Report Form (eCRF). The Screening Visit date, 
the Demography eCRF, Informed Consent eCRF, Inclusion/Exclusion Criteria eCRF and 
Subject re-screening eCRF should be completed. The Adverse Event eCRF and a SAE Form 
should be completed for any serious adverse event (SAEs) that occurred during the Screening 
Epoch. The Withdrawal of consent eCRF should be completed if consent was withdrawn prior 
to the randomization. The Death eCRF should be completed in the case of a death during the 
Screening Epoch.  
All subjects who have signed the Informed Consent Form but not entered into the next treatment 
epoch will have the study completion page for the Screening Epoch, demographics, 
inclusion/exclusion, and serious adverse event (SAE) data collected. Adverse events that are 
not SAEs will be followed by the investigator and collected only in the source data. For all 
subjects who have signed the Informed Consent Form and entered the Treatment Epochs I and 
II of the study, adverse events occurring after informed consent was signed-off should be 
recorded on the Adverse Event eCRF.  
6.2 
Subject demographics/other baseline characteristics  
6.2.1 
Demographics 
Subject demographic data will include: date of birth (might be restricted to the year only due to 
applicable local data protection regulations), gender, race, ethnicity, and child-bearing potential 
(for females only). 
6.2.2 
Psoriasis medical history/previous psoriasis therapies 
The following information should be collected and entered in the Psoriasis History eCRF in 
addition to pre-psoriasis therapies:  
• The date of first diagnosis of plaque-type psoriasis  
• The date of first diagnosis of other locations or clinical forms of psoriasis, e.g.: 
• Generalized pustular or pustular palmoplantar psoriasis 
• Guttate, palmoplantar, nail, inverse, scalp or erythrodermic psoriasis 
• The previous treatments of psoriasis (including previous use of biologic therapies, as well 
as phototherapy and/or photochemotherapy) and the reason for discontinuation  
• The presence of psoriatic arthritis and date of first diagnosis  


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6.2.3 
Smoking history 
The current and/or previous use of tobacco products will be recorded prior to randomization, as 
well as the estimated number of pack-years based on the approximate consumption per year. 
Non-smokers will be advised to not start smoking during the study. 
6.2.4 
Co-morbidities – cardiovascular medical history 
Any information pertaining to cardiovascular medical history assessed prior to randomization 
should be recorded in the eCRF. 
6.2.5 
Relevant medical history/current medical conditions 
Relevant medical history and current medical conditions present before signing the informed 
consent should be recorded in the Medical History eCRF. 
Relevant medical history/current medical condition data includes data prior to signing of the 
informed consent and until the start of study treatment. Whenever possible, diagnoses and not 
symptoms should be recorded. 
Any information pertaining to psoriasis or cardiovascular medical history assessed prior to 
randomization should be reported on the corresponding eCRF.  
6.2.6 
Determination of the tuberculosis status 
Determination of the tuberculosis (TB) status should be done at Screening  and should be 
performed as defined by local guidelines. The TB status must be determined by medical history, 
signs, symptoms, TB testing (QuantiFERON-TB Gold assay). Any significant findings should 
be recorded in the TB assessment eCRF and the Medical History eCRF, as deemed necessary.  
QuantiFERON TB-Gold In-Tube assay 
A QuantiFERON® TB-Gold In-Tube assay (QFT) to screen a population for latent tuberculosis 
infection (Doherty et al 2008) will be used at Screening to evaluate the subjects’ eligibility for 
the study. This blood-based assay is specific for Mycobacterium tuberculosis and is not 
influenced by previous Bacillus Calmette-Guérin vaccination or by exposure to other 
Mycobacteria species. Furthermore, this test, in contrast to the purified protein derivative (PPD) 
skin test, is also insensitive to a booster effect since the subject is not exposed to the vaccine.  
The assay measures the production of interferon-gamma and presents it relative to a negative 
and a positive control sample (Manuel and Kumar 2008). The QuantiFERON®-TB Gold assay 
test will be supplied by the central laboratory. Details on the collection, shipment of samples 
and reporting of results by the central laboratory are provided to investigators in the study-
specific laboratory manual. 
Positive or indeterminate tests must be recorded on the Tuberculosis assessment eCRF; the 
workflow of sample handling in case of positive or indeterminate test results is provided in 
Figure 6-1.  
• If the test result is negative, the subject may be randomized. 
• If the test result is positive, the investigator should perform a work-up for the test result as 
per local procedures. If a TB work-up was conducted prior to the screening of the subject, 


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results of the work-up can be used to assess eligibility if the work-up was conducted within 
12 weeks prior to randomization. 
• Subjects positive for latent TB per work-up may be randomized to the trial if sufficient 
treatment has been initiated according to local routine clinical practice and will be 
maintained for the prescribed duration. Subjects positive for active TB per work-up are 
not eligible for the study. Subjects negative for TB (no signs of latent or active TB) per 
work-up may be randomized to the trial. 
• If the test result is indeterminate, the investigator may repeat the test once or may 
proceed directly to perform the work-up for the test result as per local procedures. This 
action is at the discretion of the investigator. If a TB work-up was conducted prior to the 
screening of the subject, results of the work-up can be used to assess eligibility if the work-
up was conducted within 12 weeks prior to randomization. 
• If the second test is negative, the subject may be randomized. 
• If the second test is positive, the investigator should perform work-up as per local 
guidelines. Subjects positive for latent TB per work-up may be randomized to the trial 
if sufficient treatment has been initiated according to local routine clinical practice and 
will be maintained for the prescribed duration. Subjects positive for active TB per 
work-up are not eligible for the study. Subjects negative for TB (no signs of latent or 
active TB) per work-up may be randomized to the trial. 
• If the second test is again indeterminate, the investigator should perform follow-up for 
the test result as per local procedures. Subjects tested positive for latent TB per work-
up may be randomized to the trial if sufficient treatment has been initiated according to 
local routine clinical practice.  Subjects positive for active TB per work-up are not 
eligible for the study. Subjects negative for TB per work-up (no signs of latent or active 
TB) may be randomized to the trial if the work-up was conducted 12 within weeks prior 
to randomization. 
• If eligibility is being assessed with only 1 test result and a TB work-up (i.e., no second 
TB test will be performed), the TB test to assess eligibility must have been done via the 
central laboratory for the study within the Screening Epoch (within 4 weeks prior to 
randomization) and TB work-up will only be considered if it was completed within 
12 weeks prior to randomization. Subjects positive for latent TB per work-up may be 
randomized to the trial if sufficient treatment has been initiated according to local 
routine clinical practice and will be maintained for the prescribed duration. Subjects 
positive for active TB per work-up are not eligible for the study. Subjects negative for 
TB per work-up (no signs of latent or active TB) may be randomized to the trial. 


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Figure 6-1 
Tuberculosis screening flowchart 
 
6.2.7 
Other baseline characteristics 
Assessments at baseline are shown in table 6-1.  


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6.3 
Treatment exposure and compliance  
All doses of study treatment administration will be recorded on the appropriate Dosage 
Administration Record eCRF page (visit specific and summary pages). Compliance to the 
planned site administration schedule is expected to be high since the study treatment will be 
administered in the presence of the investigator or study personnel at pre-defined visits. 
Compliance will also be assessed and confirmed by a field monitor by drug accountability logs, 
by documentation and information provided by IRT and by the qualified site personnel that is 
responsible for treatment dispensation, preparation, administration and accountability. Cross-
checks should be performed in case of home administrations (H) and empty medication 
boxes/outer packing/devices should be collected for compliance checks by field monitors. 
6.4 
Efficacy 
The following order should be applied when performing the efficacy assessments at study 
visits: 
• Investigator’s Global Assessment modified 2011 (IGA mod 2011; scale from 0 – 4) 
• Psoriasis Area and Severity Index (PASI; score from 0 – 72) 
6.4.1 
Investigator Global Assessment (IGA mod 2011) 
IGA mod 2011 will be conducted for overall psoriatic disease as indicated in Table 6-2. It is 
recommended that the same evaluator conduct the assessment throughout the study whenever 
possible. 
In collaboration with health authorities, in particular the FDA, the IGA mod 2011 scale 
(Table 6-2) has been developed based on a previous version of the scale used in secukinumab 
phase II studies. The only change from the phase II scale to phase III scale was to condense the 
very severe and severe subjects into one category “severe”. The explanations/descriptions of 
the points on the scale have been improved to ensure an appropriate differentiation between 
them. 
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 Randomization 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. 


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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, the following criteria apply: 
• A subject will be eligible to participate in the study if she/he has an IGA mod 2011 score at 
the Randomization Visit of 3 or 4. 
• A subject will be considered as IGA mod 2011 0 or 1 responder if she/he achieves a score 
of 0 or 1, and improved by at least 2 points on the IGA scale at a given time point compared 
to baseline. 
6.4.2 
Assessment of total Body Surface Area (BSA) and Psoriasis Area 
Severity Index (PASI) 
The investigator or qualified designee will complete the PASI assessment as indicated in Table 
6-3. Whenever possible, PASI assessments should be performed by the same evaluator 
throughout the study. 
The total BSA affected by plaque-type psoriasis will be estimated from the percentages of areas 
affected, including head, trunk, upper limbs and lower limbs (see below for PASI assessment). 
The following calculations will be done by Novartis: each reported percentage will be 
multiplied by its respective body region corresponding factor (head = 0.1, trunk = 0.3, upper 
limbs = 0.2, lower limbs = 0.4). The resulting 4 percentages will be added up to estimate the 
total BSA affected by plaque-type psoriasis.  
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: 
• The neck is assessed as part of the head 
• The axillae and groin are assessed as part of the trunk 
• The buttocks are assessed as part of the lower limbs 
• When scoring the severity of erythema, scales should not be removed 


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Table 6-3 
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)† 
1 = slight 
1 = slight 
1 = slight 
0 = no involvement 
 
2  = moderate 
2 = moderate 
2 = moderate 
1 = > 0 - < 10 
 
3 = severe 
3 = severe 
3 = severe 
2 = 10 - < 30 
 
4 = very severe 
4 = very severe 
4 = very severe 
3 = 30 - < 50 
 
 
 
 
4 = 50 - < 70 
 
 
 
 
5 = 70 - < 90 
 
 
 
 
6 = 90 - 100 
Trunk (T)‡ 
1 = slight 
1 = slight 
1 = slight 
0 = no involvement 
 
2 = moderate 
2 = moderate 
2 = moderate 
1 = > 0 - < 10 
 
3 = severe 
3 = severe 
3 = severe 
2 = 10 - < 30 
 
4 = very severe 
4 = very severe 
4 = very severe 
3 = 30 - < 50 
 
 
 
 
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 used in this study are based on CHMP guidelines for psoriasis 
(CHMP/EWP/2454/02 2004) to assess efficacy in conjunction with Investigators’s Global 
Assessment (IGA mod 2011): 
• PASI 50 response: subjects achieving ≥ 50% improvement (reduction) in PASI score 
compared to BSL are defined as PASI 50 responders 
• PASI 75 response: subjects achieving ≥ 75% improvement (reduction) in PASI score 
compared to BSL are defined as PASI 75 responders 


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• PASI 90 response: subjects achieving ≥ 90% improvement (reduction) in PASI score 
compared to BSL are defined as PASI 90 responders 
• PASI 100 response/remission: complete clearing of psoriasis (PASI=0) 
• 
 
Because the head and neck, upper limbs, trunk and lower limbs correspond to approximately 
10%, 20%, 30% and 40% of the surface body area, respectively, the PASI score is calculated 
using the following 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 
Further details regarding the formula 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 PASI 90 responder status of all subjects will be calculated at the end of Treatment Epoch 
I, at Visit week 12.  
6.4.4 
Appropriateness of efficacy assessments 
PASI scores outcome measures, the assessment of the severity of the psoriasis symptoms and 
the extent to which the subject’s body area is affected by the disease, is mandated by the EMA 
for the clinical investigation of medicinal products for the treatment of psoriasis 
(CHMP/EWP/2454/02 2004). 
As indicated in Section 6.4.1, the IGA mod 2011 scale has been developed by Novartis in 
collaboration with health authorities, in particular the FDA. It is based on the previous version 
of the scale which was used in Phase II secukinumab studies, and has been used in all phase 
III studies. In the modified scale, the two “very severe” and “severe” have been condensed 
into a single category, “severe” and the explanations/descriptions of the points on the scale have 
been improved to ensure appropriate differentiation between the points. 
6.5 
Safety  
Blood withdrawals and safety assessments should be done prior to study treatment 
administration and should be taken as shown in Table 6-1 and in Appendix 2, Table 14-2. 
Appropriate safety assessments (e.g. evaluation of AEs and SAEs including injection site 
reactions) should be repeated after the dose is administered (Section 7). 


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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 necessary, based on medical history and/or symptoms, additional exams will be performed at 
the discretion of the investigator. 
Whenever possible, assessments for an individual subject should be performed by the same 
member of the study site staff throughout the study. 
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. Whenever possible, assessments should be performed 
by the same study site staff member throughout the study. 
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 (Mancia 
et al 2007). 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. 
Measurements will be recorded in the source documentation and the average of the two 
measurements will be entered on the Vital Signs eCRF.  
Normal blood pressure will be defined as a systolic pressure of 90 to < 120mmHg, and a 
diastolic blood pressure of 60 to < 80 mmHg under measurement conditions as 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 pre-hypertension (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). 
No specific action is pre-defined within this protocol to respond to specific abnormal vital 
signs, as it will be decided by the investigator whether and which specific action needs to be 
taken to respond to any abnormal values, taking into account the overall status of the subject.  
6.5.3 
Height and weight  
Height and body weight will be measured as listed in Table 6-1. 
Height and body weight will be measured in indoor clothing, but without shoes. Whenever, 
possible, body weight assessments should be performed by the same study site staff member; 
the same scale should be used throughout the study. 


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6.5.4 
Laboratory evaluations 
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 to 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. 
No specific action is pre-defined within this protocol to respond to specific abnormal 
laboratory values, as it will be decided by the investigator whether and which specific action 
needs to be taken to respond to any abnormal values, taking into account the overall status of 
the subject.  
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 as  specified in Table 6-1. 
6.5.4.2 
Clinical chemistry 
Serum chemistry will include urea, creatinine, total bilirubin, AST (SGOT), ALT (SGPT), 
GGT, alkaline phosphatase, sodium, potassium, bicarbonate, calcium, phosphorous, total 
protein, albumin, uric acid, amylase and lipase. Serum chemistry will be measured at all 
scheduled study visits as specified in Table 6-1. 
6.5.4.3 
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. 
6.5.4.3.1 High sensitivity C-reactive protein 
High sensitivity C-reactive protein (hsCRP) will be assessed using a fasting blood sample at 
baseline as indicated in Table 6-1. 
6.5.4.3.2 Lipid panel 
A lipid profile including High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), 
total cholesterol and triglycerides will be measured from a fasting blood sample at 
Baseline/Randomization as indicated in Table 6-1. 
6.5.4.3.3 Glucose 
Glucose will be assessed as indicated in Table 6-1. 


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6.5.4.4 
Urinalysis 
Dipsticks will be provided by the central laboratory to the study sites for local urinalysis 
assessments. 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. If needed conditional 
microscopy assessments will be optional. 
 
 
6.5.5 
Electrocardiogram (ECG)  
A standard single 12-lead ECG will be collected at Screening. The investigator/qualified site 
staff must review and initial the tracing. The original ECGs appropriately signed, should be 
collected and archived at the study site. 


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ECGs must be recorded after 10 minutes rest in the supine position to ensure a stable baseline. 
The preferred sequence of cardiovascular data collection during study visits is ECG collection 
first, followed by vital signs, and blood sampling. The Fridericia QT correction formula (QTcF) 
should be used for clinical decisions. 
ECG tracing filed in the study site source documents. ECGs with subject safety concerns, two 
additional ECGs should be performed to confirm the safety finding. Although there is no 
exclusion criterion based on ECG results, the ECG at Screening must be reviewed for major 
abnormalities prior to enrollment into the study. 
Clinically significant abnormalities should be recorded on the relevant section of the Medical 
History/Cardiovascular History/Current medical conditions/AE eCRF page as appropriate. 
6.5.6 
Pregnancy  
A serum β-hCG test will be performed at Screening in all pre-menopausal women who are not 
surgically sterile. In addition, all women who are not sterilized or are of childbearing potential 
at Screening, a local urine pregnancy test must be performed as indicated in Table 6-1.  
Any woman with a confirmed positive pregnancy test during Screening is not eligible for 
randomization. A positive urine pregnancy test during the treatment epochs of the study 
requires immediate interruption of study treatment until a 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 study after follow-up assessments have been performed. 
6.5.7 
Appropriateness of safety measurements  
The safety assessments selected are standard measures for a biologic immunomodulating agent 
in Psoriasis. 
6.6 
Other assessments 
The following additional assessments will be performed: 
• Clinician Reported Outcomes (ClinRO): 
Usability and hazard assessment of the pre-filled syringe 
• Patient Reported Outcomes – (PRO) 
Subject satisfaction assessment of Self-Injection Questionnaire (SIAQ) 
Dermatology Life Quality Index (DLQI) 
 
• Pharmacokinetics 


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6.6.1 
Clinical Outcome Assessments (COAs)  
6.6.1.1 
Clinician Reported Outcomes (ClinRO) 
6.6.1.1.1 Usability and hazard assessment of the pre-filled syringe (2 mL syringe) 
The goal is to measure and evaluate the usability of the pre-filled syringe during observed use. 
The assessment of the ability to follow the Instructions For Use (IFU) will be performed for the 
first of the 2 mL injection at the two respective visits as well as the assessment of the hazards 
will be performed as a summary assessment for the 2 mL injection. 
Subjects will be instructed at Randomization through the site staff on how to self-inject via pre-
filled syringes following the Instructions For Use (IFU). After explanations/instructions given 
at the Randomization Visit, the injection will be self-administered by the subject into the 
appropriate injection site of the body. The delivery of the dose will be observed by 
investigator/site staff based on observation check lists at Randomization and Visit Week 1 
together with an assessment of potential administration hazards based on identified hazards list 
as well as non-directed querying for any observed problems during self-injection (Table 6-5). 
Primary usability assessment:  
• Assessment of successful self-administration by the subject at Visit Week 1, by studying 
the number and percentage of subjects who successfully perform this self-injection (note: 
without prior explanations/instructions at this visit, as this has been performed prior to 
dosing at Randomization only). Successful self-injection is achieved when the subject 
performs all required steps effectively and safely to deliver the correct dose from the device 
at the correct injection site. The sequence of user steps as per IFU being minimally required 
are 1) removing the needle cap; 2) pinch the skin at injection site; 3) insert needle into skin; 
4) hold onto the finger flange; 5) fully depress plunger until end point; 6) hold the device in 
position for 5 seconds. As per Table 6-4 below, these 6 critical steps will be used to define 
successful administration. The general passing usability goal for ‘successful use’ task 
completion will be defined as ≥ 90% pass rate of following these steps.  
Secondary usability assessment:  
• Assessment of subject use errors that occur during the First Use at Randomization (after 
providing initial explanations/instructions) and repeated self-injection at Visit Week 1 
(without a detailed explanation/instruction on handling the new form) by investigating the 
frequency of observed or reported difficulties in completing the self-injection after initial 
explanations/instructions and self-injection without explanations/instructions after a time 
lag that represents standard treatment. The number and percentage of subjects who 
successfully complete each of the indicated steps as per the IFU (Table 6-4 self-injection 
assessment check list) as well as the number and percentage of subjects who experience any 
of the defined possible hazards (based on identified hazards list) as well as non-directed 
querying for any observed problems during self-injection (Table 6-5) will be computed by 
visit. 


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• Assessment of successful First Use by subject after initial explanations/instructions, by 
studying the number and percentage of subjects at Randomization who successfully perform 
the self-injection as defined above for the primary usability assessment. 
The First Use at Randomization and the Week 1 assessments will take place in the context of 
an observed assessment under the supervision of one site staff member. Each assessment will 
be conducted on a 1:1 basis. At the Randomization visit the subjects will be instructed through 
the site staff by walking them through the Instructions For Use (IFU) on how to self-inject via 
pre-filled syringe. Subjects will then be asked to raise any questions if they have any. Thereafter, 
they should proceed with self-injection. At Visit Week 1 subjects will be asked to refer to the 
IFU and to proceed with self-injection of the actual study drug (i.e., without providing 
explanations/instructions). During the first self-injections at the respective visits 
(Randomization and Week 1) site staff will observe and complete the self-injection assessment 
checklist (Table 6-4) at the first of the injections at each visit (for the 2 mL form). The possible 
hazard assessment check list (Table 6-5) will be assessed for the injections at each of the 
applicable visits for the 2 mL form. The primary usability variables will be assessed based on 
binary (performed correctly: yes/no) response for the self-injection assessment check list (Table 
6-4). The possible hazard check list variables will be mainly assessed based on binomial 
(occurred: yes/no) response. Additionally, responses from the directed and non-directed 
querying for any observed problems and specification thereof during self-injection will be 
analysed on a case by case basis. For each item of the assessment checklists, the number and 
percentage of subjects with each response will be summarized. Where relevant, the number, 
percentage, average, standard deviation, minimum and maximum shall be presented. 
Table 6-4 
Self-injection assessment check list (2 mL syringe) 
No. 
IFU indicated steps 
Required to be 
completed for 
successful 
administration 
P1 
Washed hands with soap and water 
No 
P2 
Cleaned the injection site 
No 
P3 
Removed the safety syringe from the outer box  
No 
P4 
Took syringe out of the tray 
No 
P5 
Checked expiration date on syringe label 
No 
P6 
Inspected the safety syringe for damage 
No 
P7 
Inspected liquid for brown discoloration or particles 
No 
P8 
Removed needle cap from safety syringe 
Yes 
P9 
Discarded needle cap 
No 
P10 
Pinched the skin at injection site 
Yes 
P11 
Inserted the needle into skin 
Yes 
P12 
Held onto the finger flange 
Yes 
P13 
Fully depressed plunger until end point 
Yes 
P14 
Held plunger pressed fully down and syringe in place for 5 seconds 
Yes 
P15 
Kept plunger fully depressed while lifting the needle straight from 
injection site 
No 
P16 
Released the plunger  
No 


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No. 
IFU indicated steps 
Required to be 
completed for 
successful 
administration 
P17 
Allowed syringe guard to automatically activate and cover the needle 
No 
P18 
Disposed used safety syringe in a sharps container 
No 
 
Table 6-5 
Possible hazard assessment check list (2 mL syringe) 
No. 
Possible Use related hazards 
H1 
Was there a needle stick in a critical area (e.g. eye, carotid artery)? 
H2 
Was there a needle stick in a non-critical area1? 
H3 
Was any part of the device swallowed? If yes, please specify. 
H4 
Was an immediate type allergic reaction noticed to device material? 
H5 
Was increased pain noticed by the patient due to bent needle? 
H6 
Was there breakage of the device observed?2 
H7 
Was swallowing of material debris observed?3 
H8 
Was any other problem observed?3 
H9 
Was less than the full dose administered?4 
 
1 Excluding the actual injection into the appropriate injection site of the body 
2If yes, then it is to be specified under which circumstances breakage occurred and which parts were affected, as well any 
additional problems (e.g. injuries) due to the breakage are to be described. 
3If yes, then it is to be specified. Possible events might include: irritated skin; drug too cold when injected; the drug or device 
upon visual inspection appeared unsuitable for injection; intradermal instead of subcutaneous injection; and other events. 
4If yes, then it is to be specified why, e.g. leakage from injection site, early removal. 
During the self-injection the observing site staff member must exercise judgment and intervene 
in the self-administration should a subject not be acting in a safe or reasonable manner, or any 
manner which does not fall within the scope of the study objectives, including but not limited 
to: 
a. In the event that a subject performs (or is judged to be about to perform) a use error which 
could pose a risk to the health or well-being of a subject the observing site staff member 
will pause the subject to point out the error and decide whether it is better to terminate the 
self-injection. If in his or her judgment the self-injection can continue, he or she will 
correct the subject’s usage of the product and notify the subject to recommence at the 
same point. Any such use error will be documented. 
b. If there is, or appears to be, any risk of a health and safety incident including injury to any 
party. It is likely that this will require the self-injection to be terminated at the discretion 
of the observing site staff member. 
Any pre-filled syringe for which a defect or malfunction is noticed prior to or during the 
injection at any of the study visits, must be kept at the site until guidance is received from 


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Novartis on whether it should be returned to Novartis or discarded. Additionally, from Visit 
Week 2 onwards, any noticed defect, malfunction, and problem during the injections or product 
complaints with the pre-filled syringe should be recorded in the source document by the site, 
detailing the issue, the date and the visit number. It should also be reported to Novartis. 
Similarly, during Treatment Epochs I and II, if such defects, malfunctions, problems during 
injections or product complaints are noticed by subjects during home administration, they 
must immediately be reported back to the sites, documented in detail in the source documents 
and reported to Novartis. 
6.6.1.2 
Patient Reported Outcomes (PRO) 
6.6.1.2.1 Subject satisfaction assessment of Self-Injection Questionnaire (SIAQ) –  
2 mL syringe 
The Self-Injection Assessment Questionnaire (SIAQ) measures the overall subject experience 
with subcutaneous self-injection, and to investigate the psychometric properties (Keininger and 
Coteur 2011, Appendix 4). The SIAQ will be performed as a summary assessment for the 2 mL 
syringe at the visits as outlined in the visit schedule (see Table 6-1). 
The SIAQ PRE module is to be self-completed before the first self-injection at Randomization. 
The SIAQ POST module is to be completed following the self-injections as the visits indicated 
in Table 6-1, including Randomization. The PRE module includes 7 items grouped into three 
domains: Feelings about injections, Self-confidence and Satisfaction with self-injection, the 
POST module includes several items addressing four principal domains: Feelings about 
injections, Self-confidence, Injection-site reactions, Ease of use plus a single item assessing 
Self-image (see Table 6-1).  
The two modules of the SIAQ should be completed by subjects while alone in a quiet 
environment. The PRE module is completed immediately before the first self-injection and the 
POST module is completed 20-40 minutes after dosing (three injections). There is no stipulated 
recall period for the SIAQ, because the recall period varies from one domain to another. For 
example, items from the injection-site reaction burden domain refer to the subject’s experience 
during or after the injection, whereas items from the general feelings about injections domain 
refer to general attitudes. Subjects should rate each item of the SIAQ on a 5-point semantic 
Likert-type scale, where a score of 1 corresponded to the subject’s worst experience and a score 
of 5 corresponds to the subject’s best experience. Item scores will be transformed to obtain a 
score ranging from 0 (worst experience) to 10 (best experience) for each item. The domain score 
will be the mean of the item scores included in the domain. Domain scores will be calculated 
only if at least half of the domain items were completed. 
The SIAQ questionnaire (date of publication 2011) will be completed by the subject as indicated 
in Table 6-1. 
6.6.1.2.2 Health-related quality of life (HRQOL) questionnaires  
The impact of psoriasis on various aspects of subject’s health-related quality of life (HRQOL) 
will be assessed by the following validated instruments: 
• Dermatology Life Quality Index (DLQI)  


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• 
 
These questionnaires should be completed by subjects before they see the study physician 
(investigator or designee) who will perform the investigator assessments.  
All questionnaires will be completed in the language the respondent is most familiar with, at 
the scheduled visit before the subject sees the investigator for clinical assessments. The subject 
should be given sufficient space and time to complete the questionnaires. The study coordinator 
should check the questionnaires for completeness and encourage the subject to complete any 
missing responses.  
Completed questionnaires will be reviewed and examined by the investigator only after the 
clinical efficacy assessments (PASI, IGA mod 2011 
), for responses that may 
indicate potential AEs or SAEs. The investigator should review not only the responses to the 
questions in the questionnaires but also for any unsolicited comments written by the subject. If 
AEs or SAEs are confirmed then the investigator must record the events as per instructions 
given in Section 7 of the protocol. Investigator should not encourage the subject to change the 
responses reported in the completed questionnaires. 
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, Appendix 5). 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 purpose of the DLQI in this study is to investigate the effects of treatment of secukinumab 
with respect at Week 12, compared to placebo, and over time up to Week 52, compared to 
placebo. 
The DLQI questionnaire (version 2, date of publication 1994) will be completed by the subject 
as indicated in Table 6-1. 


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6.6.3 
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 Collection Log in Appendix 2, Table-14.1. 
Blood samples (approximately 2 mL, not less than 1.5 mL) will be collected into Serum 
Separator Tubes (SST). All blood samples will be taken by direct venipuncture. 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 approx. 2,500 
Revolutions Per Minutes (RPM) for 10 minutes. 
Thereafter, the serum samples will be placed on ice, split into 2 aliquots (labelled plain barrier 
polypropylene tubes) and then stored (within 30 minutes of serum collection by centrifugation) 
at -70˚C to -20˚C. The shipment to the central laboratory should be made on dry ice. The 
shipment instructions will be provided by the central laboratory. If possible, each aliquot of a 
sample should be sent separately to the central laboratory. The back-up samples should remain 
at the central laboratory whereas the second batch (the second pair) is delivered to an analytical 
laboratory. Back-up samples at the central laboratory will only be disposed after approval by 


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the corresponding Study Leader (typically six to 12 months after the clinical study report is 
published).  
The actual sample collection date and exact time of collection should be entered in the blood 
collection for PK eCRF or in the Unscheduled blood collection for PK eCRF, as appropriate. 
Sampling problems should be noted in the ‘Reason sample not taken’ section of the eCRF. 
6.6.3.1 
PK sample handling, labeling and shipment instructions 
A laboratory manual will be provided by the central laboratory with detailed information about 
sample collection, handling and shipment. 
Tubes and labels will be provided by the central laboratory with study/sample type and sample 
number pre-printed on the label. 
6.6.3.2 
PK sample stability  
Secukinumab is stable in serum samples for 4 months at -20°C or at -80°C. Long-term data 
confirmed a stability of 39 months at -65°C to -90°C. 
6.6.3.3 
PK analytical methods 
An ELISA method will be used for the bioanalytical analysis of AIN457 in serum, with an 
anticipated lower limit of quantification (LLOQ) of 80 ng/mL. The detailed method description 
to assess the Secukinumab concentration will be described in the bioanalytical raw data of the 
study and in the respective Bioanalytical Data Report (BDR). 
7 
Safety monitoring  
7.1 
Adverse events  
An adverse event (AE) is any untoward medical occurrence (e.g., 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 until the end of study visit. Therefore, an AE may or may not be temporally or causally 
associated with the use of a medicinal (investigational) product. 
In addition, all reports of intentional misuse and abuse of the product are also considered an 
adverse event irrespective if a clinical event has occurred. 
The occurrence of adverse events must be sought by non-directive questioning of the subject at 
each visit during the study. Adverse events also may be detected when they are volunteered by 


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the subject during or between visits or through physical examination findings, laboratory test 
findings, or other assessments. 
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 must 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 subject with 
underlying disease. Investigators have the responsibility for managing the safety of individual 
subject and identifying adverse events. Alert ranges for laboratory and other test abnormalities 
are included in Appendix 1. 
Adverse events must be recorded in the Adverse Events eCRF 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 study treatment (suspected: no/yes) 
• Its duration (start and end dates) or if the event is ongoing an outcome of 
not recovered/not resolved must be reported. 
• Whether it constitutes a serious adverse event (SAE - Section 7.2 for definition of SAE) 
and which seriousness criteria have been met. 
• Action taken regarding study treatment  
All adverse events must be treated appropriately. Treatment may include one or more of the 
following:  
• No action taken (e.g. further observation only)  
• Study treatment dosage increased/reduced  
• Study treatment interrupted/withdrawn  
• Concomitant medication or non-drug therapy given  
• Subject hospitalized/subject’s hospitalization prolonged (Section 7.2 for definition of 
SAE) 
• Its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown) 
Once an adverse event is detected, it must be followed until its resolution or until it is judged to 
be permanent, and assessment must be made at each visit (or more frequently, if necessary) of 
any changes in severity, the suspected relationship to the study drug, the interventions required 
to treat it, and the outcome. 


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Worsening of psoriasis in this study is evaluated via the use of PASI, IGA mod 2011 and DLQI 
assessments and is not expected to be captured as an AE in the eCRF. Exceptions include cases 
when a) a new type of psoriasis is diagnosed e.g. guttate psoriasis) or b) the worsening of 
psoriasis is so severe that a qualitatively different status is reached. 
Information about common side effects already known about the investigational drug can be 
found in the Investigator’s Brochure (IB). This information will be included in the subject 
informed consent and should be discussed with the subject during the study as needed. Any new 
information regarding the safety profile of the medicinal product that is identified between IB 
updates will be communicated as appropriate, for example, via an Investigator Notification (IN) 
or an Aggregate Safety Finding. New information might require an update to the informed 
consent and has then to be discussed with the subject. 
The investigator must also instruct each subject to report any new adverse event (beyond the 
protocol observation period) that the subject, or the subject’s personal physician, believes might 
reasonably be related to study treatment. This information must 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 events  
7.2.1 
Definition of SAE  
A serious adverse event (SAE) is defined as 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 (specify what this includes) 
• 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 subject’s 
general condition 
• Is medically significant, e.g. defined as an event that jeopardizes the subject or may 
require medical or surgical intervention. 
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. 


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Life-threatening in the context of a SAE refers to a reaction in which the subject was at risk of 
death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (Annex IV, ICH-E2D Guideline). 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life threatening or result in death or hospitalization but might jeopardize the subject or might 
require intervention to prevent one of the other outcomes listed above. Examples of such events 
are intensive treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization or development of dependency or 
abuse (Annex IV, ICH-E2D Guideline). 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
7.2.2 
SAE reporting  
To ensure subject safety, every SAE, regardless of causality, occurring after the subject has 
provided informed consent and until 12 weeks following the last administration of study 
treatment must be reported to Novartis within 24 hours of learning of its occurrence. Any SAEs 
experienced after the 12 weeks period following the last administration of study treatment 
should only be reported to Novartis if the investigator suspects a causal relationship to study 
treatment. Any SAEs reported up to the subject’s last visit will be reported in the AE eCRF. 
SAEs beyond that date will only be recorded in the Novartis Drug Safety and Epidemiology 
database. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
within 24 hours of the investigator receiving the follow-up information. An SAE occurring at a 
different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event. 
Information about all SAEs is collected and recorded on the Serious Adverse Event Report 
Form; all applicable sections of the form must be completed in order to provide a clinically 
thorough report. The investigator must assess the relationship of each SAE to each specific 
component of study treatment (if study treatment consists of several components), complete 
the SAE Report Form in English, and submit the completed form within 24 hours to Novartis. 
Detailed instructions regarding the submission process and requirements for signature are to be 
found in the investigator folder provided to each site.  
Follow-up information is submitted as instructed in the investigator folder. Each re-occurrence, 
complication, or progression of the original event must be reported as a follow-up to that event 
regardless of when it occurs. The follow-up information should describe whether the event has 
resolved or continues, if and how it was treated, whether the blind was broken or not, and 
whether the subject continued or withdrew from study participation.  
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert (new 
occurrence) and is thought to be related to the study 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 


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investigators involved in any study with the same study 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 EU 
Guidance 2011/C 172/01 or as per national regulatory requirements in participating countries. 
7.3 
Liver safety monitoring 
Not applicable.  
7.4 
Renal safety monitoring 
Not applicable.  
7.5 
Reporting of study treatment errors including misuse/abuse 
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, subject or 
consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol. 
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol will be collected in 
the Dose Administration Record (DAR) eCRF irrespective of whether or not associated with an 
AE/SAE and reported to Safety only if associated with an SAE. Misuse or abuse will be 
collected and reported in the safety database irrespective of it being associated with an AE/SAE. 
Table 7-1 
Guidance for capturing the study treatment errors including 
misuse/abuse 
 
Treatment error 
type 
Document in Dose 
Administration 
(DAR) eCRF (Yes/No) 
Document in AE 
eCRF 
Complete SAE form 
Unintentional study 
treatment error 
Yes 
Only if associated with 
an AE 
Only if associated with an 
SAE 
Misuse/Abuse 
Yes 
Yes  
Yes, even if not 
associated with a SAE 
7.6 
Pregnancy reporting  
To ensure subject safety, each pregnancy occurring after signing the informed consent must be 
reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed-up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications. 


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Pregnancy must be recorded on the Pharmacovigilance Pregnancy Form and reported by the 
investigator to the local Novartis Drug Safety and Epidemiology (DS & E) 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 and unrelated to the pregnancy must be reported on 
the SAE Report Form. 
8 
Data review and database management  
8.1 
Site monitoring  
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and eCRFs with the investigators and their staff. During 
the study, Novartis employs several methods of ensuring protocol and Good Clinical Practice 
(GCP) compliance and the quality/integrity of the sites’ data. The field monitor will visit the 
site to check the completeness of subject records, the accuracy of entries on the eCRFs, the 
adherence to the protocol and to GCP, 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. Continuous remote 
monitoring of each site’s data may be performed by a centralized Novartis CRA organization. 
Additionally, a central analytics organization may analyze data & identify risks & trends for 
site operational parameters, and provide reports to Novartis Clinical Teams to assist with trial 
oversight. 
The investigator must maintain source documents for each subject 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 eCRFs must be traceable to these source documents in the 
subject's file. The investigator must also keep the original Informed Consent Form signed by 
the subject (a signed copy is given to the subject). 
The investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the eCRF entries. Novartis monitoring standards require full verification for 
the presence of informed consent, adherence to the inclusion/exclusion criteria, documentation 
of SAEs, and of data that will be used for all primary variables. Additional checks of the 
consistency of the source data with the eCRFs are performed according to the study-specific 
monitoring plan. No information in source documents about the identity of the subjects/subjects 
will be disclosed. 
8.2 
Data collection  
Designated investigator staff will enter the data required by the protocol into the 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 subject data for archiving at the 
investigational site.  
8.3 
Database management and quality control 
Novartis staff [or Contract Research Organization (CRO) working on behalf of Novartis] 
review the data entered into the eCRFs 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 reviewed locally.  
Randomization codes and data about all study drug(s) dispensed to the subject 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.  
The occurrence of relevant protocol deviations will be determined. After these actions have 
been completed and the database has been declared to be complete and accurate, it will be 
locked and the treatment codes will be unblinded and made available for data analysis. Any 
changes to the database after that time can only be made after written agreement by Novartis 
Development management. 
8.4 
Data Monitoring Committee  
Not planned.  
8.5 
Adjudication Committee  
Not planned.  


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9 
Data analysis  
The analysis will be conducted on all subject 
 
 data at the time of the trial ends. Any data analysis 
carried out independently by the investigator should be submitted to Novartis before publication 
or presentation. 
Treatment groups for analyses will include: 
• Week 12: secukinumab 300 mg (two 1 mL injections of 150 mg s.c.), secukinumab 
300 mg (one 2 mL s.c. injection), and placebo  
• Week 12 up to Week 52 (end of study): secukinumab 300 mg (two 1 mL injections of 
150 mg s.c.), secukinumab 300 mg (one 2 mL s.c. injection), placebo-secukinumab 300 
mg (two  1 mL injections of 150 mg) and placebo-secukinumab 300 mg (one 2 mL s.c. 
injection) 
• Entire study: secukinumab 300 mg (two 1 mL injections of 150 mg s.c.), secukinumab 
300 mg (one 2 mL s.c. injection), placebo, any secukinumab 300 mg (two 1 mL injections 
150 mg s.c.), any secukinumab 300 mg (one 2 mL s.c. injection) 
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. 
9.1 
Analysis sets  
The following analysis sets will be used in this study: 
Randomized set: The randomized set will be defined as all subjects who were randomized. 
Unless otherwise specified, mis-randomized subjects (mis-randomized in IRT) will be excluded 
from the randomized set. (mis-randomized subjects are defined as cases where IRT contacts 
were made by the site either prematurely or inappropriately prior to confirmation of the 
subject’s final randomization eligibility and double-blind medication was not administered to 
the subject). 
Full analysis set (FAS): The FAS will be comprised of all subjects from the randomized set to 
whom study treatment has been assigned. Following the intent-to-treat (ITT) principle, subjects 
will be analyzed according to the treatment assigned to at randomization.  
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 
Subject demographics and other baseline characteristics  
Unless otherwise specified, for subject demographics and other baseline characteristics, 
analyses will be based on the randomized set. 
9.2.1 
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 


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percentage of subjects in each category will be presented for categorical variables for each 
treatment group and all subjects. 
9.2.2 
Medical history 
Any condition entered as medical history or current medical conditions at baseline will be coded 
using the MedDRA dictionary. They will be summarized by system organ class and preferred 
term of the MedDRA dictionary. Summaries for cardiovascular and psoriasis specific medical 
history will be provided as well. 
9.3 
Treatments  
9.3.1 
Study treatment 
The analysis of study treatment data will be based on the safety set.  
The duration of exposure to study treatment will be summarized by treatment group. In addition, 
the number of subjects with exposure of at least certain thresholds (e.g. any exposure, ≥ 1 week, 
≥ 2 weeks, ≥ 3 weeks, ≥ 4 weeks, ≥ 8 weeks, etc.) will be displayed.  
Duration of exposure of a treatment will be defined as the time from first dose of the treatment 
to the time of treatment switch (for subjects who switch treatment) or minimum of (last dose of 
the treatment + 84 days) and (last visit date).  
9.3.2 
Prior and concomitant medication 
Prior and concomitant medications will be summarized by treatment group for the different 
epochs in separate tables. 
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 last day of study visit will be a concomitant medication, including those which 
were started pre-baseline and continued into the treatment period.  
Medications will be presented in alphabetical order, by Anatomical Therapeutic Classification 
(ATC) codes and grouped by anatomical main group. Tables will also show the overall number 
and percentage of subjects receiving at least one treatment of a particular ATC code and at least 
one treatment in a particular anatomical main group.  
Psoriasis specific pre-study treatments, number of pre-study systemic and biologic psoriasis 
therapies as well as reason for discontinuation will be presented. 
In addition, medical procedures and significant non-drug therapies as coded in MedDRA will 
be summarized. 
9.4 
Analysis of the primary variable(s) 
Details of the testing strategy including primary endpoints are provided in Section 9.4.2. 


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9.4.1 
Co-primary Variable(s) 
The co-primary efficacy variables are PASI 75 response at Week 12 and IGA mod 2011 0 or 1 
response at Week 12. The analysis of the co-primary variables will be based on the full analyses 
set (FAS). 
9.4.2 
Statistical model, hypothesis, and method of analysis 
9.4.2.1 
Primary endpoint (co-primary endpoints) 
The co-primary endpoints of this study are PASI 75 response and IGA mod 2011 0 or 1 response 
at Week 12. 
The statistical hypotheses are that secukinumab 300 mg (2 mL s.c. injection) is not superior to 
placebo with respect to the proportion of subjects with PASI 75 response and IGA mod 2011 0 
or 1 response at Week 12. 
Let 𝑝𝑝𝑗𝑗 denote the proportion of PASI 75 responders at Week 12 for treatment group j and 𝑟𝑟𝑗𝑗 
denote the proportion of IGA mod 2011 0 or 1 responders at Week 12 for treatment group j, 
j = 1,0. where 
• 0 corresponds to placebo 
• 1 corresponds to secukinumab 300 mg (2 mL s.c. injection) 
The following hypotheses will be tested: 
• 𝐻𝐻1: 𝑝𝑝1 −𝑝𝑝0 ≤0 versus 𝐻𝐻𝐴𝐴1: 𝑝𝑝1 −𝑝𝑝0  > 0, 
• 𝐻𝐻2: 𝑟𝑟1 −𝑟𝑟0 ≤0  versus 𝐻𝐻𝐴𝐴2: 𝑟𝑟1 −𝑟𝑟0  > 0  
In other words: 
H1: Secukinumab 300 mg (2 mL s.c. injection) is not superior to placebo with respect to PASI 
75 response at Week 12 
H2: Secukinumab 300 mg (2 mL s.c. injection) is not superior to placebo with respect to IGA 
mod 2011 0 or 1 response at Week 12 
The primary analysis method will be the exact logistic regression with treatment group; baseline 
bodyweight and baseline PASI score as explanatory variables. Odds ratios will be computed for 
comparisons of secukinumab dose regimen versus placebo in a pairwise fashion utilizing the 
logistic regression model fitted. In case of response rates of 0% or of 100% in one of the 
treatment groups, Fisher’s exact test will be applied. Confidence intervals for risk difference 
will be derived based on the exact method. 
The hypotheses 𝐻𝐻1 and 𝐻𝐻2 will both be tested at level 2.5% (one-sided), and significant results 
will only be achieved if both tests are rejected. If only one hypothesis is rejected and the other 
hypothesis is not rejected, superiority of secukinumab 300 mg (2 mL s.c. injection) has not been 
demonstrated.  
9.4.3 
Handling of missing values/censoring/discontinuations 
The following imputation methods will apply to the missing data: 


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• Response variables based on PASI score and IGA mod 2011 categories will be imputed 
with multiple imputations (MI) method as primary imputation method. 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 or IGA mod 2011 
categories will be imputed 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.   
• Non-responder imputation will be used as sensitivity method: Missing values with respect 
to response variables based on PASI score and IGA mod 2011 categories will be imputed 
with non-response regardless to the reason for missing data (e.g. premature study 
discontinuation, missed visit, administrative issues), exceptions will apply to the following: 
• If a subject who was responder at visit x-1 and visit x+1 but has missing data at visit x, 
then the subject will be imputed for visit x.  
• If a subject dropped out of the study prior to last scheduled visit and being responders 
consecutively at least for two preceding visits, the subject will be imputed as responder 
for the last scheduled visit. 
9.4.4 
Sensitivity analyses 
Sensitivity analyses will be performed as follows: 
Co-primary variables will be evaluated using the exact logistic regression as described in 
primary analysis method with non-responder imputations. 
9.5 
Analysis of key secondary variables 
9.5.1 
Efficacy variables  
9.5.1.1 
The key secondary endpoints of this study are planned as follows: 
• PASI 90 response at Week 12 
• PASI 100 response at Week 12 
9.5.1.2 
Testing strategy 
The following hypotheses will be tested sequentially and are included in the hierarchical testing 
strategy and type-I-errors will be set such that a family-wise type-I-error of 2.5% (one-sided) is 
kept: 
• H1: secukinumab 300 mg (2 mL s.c. injection) is not superior to placebo with respect to 
PASI 75 response at Week 12 
• H2: secukinumab 300 mg (2 mL s.c. injection) is not superior to placebo with respect to 
IGA mod 2011 0 or 1 response at Week 12 
• H3: secukinumab 300 mg (2 mL s.c. injection) is not superior to placebo with respect to 
PASI 90 response at Week 12 


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• H4: secukinumab 300 mg (2 mL s.c. injection) is not superior to placebo with respect to 
PASI 100 response at Week 12 
• H5: secukinumab 300 mg (two 1 mL s.c. injections of 150 mg secukinumab) is not 
superior to placebo with respect to PASI 100 response at Week 12 
The graphical approach of (Bretz et al 2009) for sequentially rejective testing procedures is used 
to illustrate the testing strategy: 
Figure 9-1 
Testing strategy 
 
The efficacy variables involved in the above testing strategy will be analyzed analogously to 
the primary endpoints at Week 12, i.e., the exact logistic regression model with treatment group, 
baseline bodyweight and baseline PASI score as exploratory variables. Odds ratios will be 
computed for comparisons of secukinumab versus placebo utilizing the logistic regression 
model fitted. 
The testing sequence will continue to H3 at α (one-sided) only if both H1 and H2 have been 
rejected at α (one-sided). Similarly, the testing sequence will continue to H4 at α (one-sided) 
only if H3 testing has been rejected. In case, H4 has been rejected at α (one-sided), the 
corresponding alpha (α) will be passed to the next hypothesis corresponding to H5. 
9.6 
Analysis of other secondary and exploratory variables 
9.6.1 
PASI 50, PASI 75, PASI 90, PASI 100 and IGA mod 2011 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 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 exact 
method. 
For PASI 50, PASI 75, PASI 90, PASI 100 and IGA mod 2011 0 or 1 response at each visit, 
pairwise comparison between each secukinumab dose regimen and placebo will be conducted 
using exact logistic regression model with treatment group, body weight stratum, and baseline 
PASI as effects. 


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Figures will be provided as well displaying estimates for responder rates by treatment including 
confidence intervals. 
9.6.2 
PASI score over time 
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. 
9.6.3 
IGA mod 2011 score over time 
Summary statistics for the IGA mod 2011 score over time will be presented by visit and by 
treatment group in contingency tables. Figures will also be provided. 
 
 
 
 
 
 
 
 
 
 
 
9.6.6 
Safety variables  
All safety evaluations will be performed on the safety set. 
Analysis of adverse events will be based on treatment emergent events, which are defined as 
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. 
Other safety variables will be based on on-treatment events, which are defined as any events 
that happened after first dose of study treatment and on or before last dose + 84 days. 
9.6.6.1 
Adverse events 
Treatment emergent adverse events (AEs) will be summarized for each treatment group by 
presenting the number and percentage of subjects with all/any AEs, AEs in each primary system 
organ class and 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 highest 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 highest severity at the system organ 
class level, where applicable.  
Tabulated summaries will be presented for Treatment Epoch I and all epochs put together. 


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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 study treatment discontinuation. 
A graphical display of relative frequencies within system organ classes will be presented. 
Exposure adjusted analyses in terms of incidence rate will be provided combining all the study 
epochs. 
9.6.6.2 
Laboratory data 
The summary of laboratory evaluations will be presented for three groups of laboratory tests 
(hematology and serum chemistry). 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.  
Shift tables with respect to Common Toxicity Grade Criteria (CTCG) and normal ranges will 
be provided. These summaries will be presented by laboratory test and treatment group. Shifts 
will be presented for most extreme values post-baseline. 
Incidence rates of notable abnormalities will be presented (Appendix 1). 
 
 
 
9.6.6.4 
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 signs and treatment group. Change from baseline will only be summarized for subjects 
with both baseline and post-baseline values. 
All information collected will be listed by subject and abnormal values will be flagged 
(Appendix 1). 
9.6.7 
Health-related Quality of Life 
9.6.7.1 
Dermatology Life Quality Index (DLQI) 
Summaries will be based on the FAS and will be presented separately for each treatment group.  
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. 
The absolute value and the percentage change from baseline of DLQI total score will be 
analyzed with the Van-Elteren test using type-II weights, for between-treatment comparison of 


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the two secukinumab treatment groups versus placebo. The Van-Elteren test will be performed 
at each visit. Language of the questionnaire and geographical region will be the strata adjusted 
for in the Van-Elteren test. In addition, stratified Hodges-Lehmann estimates for the median as 
well as confidence intervals will be derived for the absolute values and percentage change to 
baseline for each treatment group as well as for treatment comparison between two 
secukinumab treatment groups versus placebo. 
It is understood that conclusions obtained from the confidence intervals of these estimates 
(mean or Hodges-Lehmann estimates for the median) will not be completely consistent with the 
testing results (Van-Elteren test) which constitute the key analysis for drawing conclusions. 
In addition, summary statistics will be provided for number of subjects achieving DLQI 0 or 1. 
Treatment groups will be compared by means of Fisher’s exact test. 
9.6.8 
Patient Reported Outcomes (PRO) 
9.6.8.1 
Subject satisfaction assessment of Self-Injection Questionnaire (SIAQ) 
Summary statistics for the domain scores as well as item scores will be provided by visit and 
treatment group. 
Item and domain scores from the PRE module taken before the first self-injection at 
Randomization will be compared with the corresponding item and domain scores (Feelin about 
injections, Self-confidence domains and overall satisfaction of self-injection item) from the 
POST module taken after the two self-injections. Change in domain scores from PRE module 
will be summarized by visit and treatment group. 
9.6.10 
Pharmacokinetics  
All completed subjects with quantifiable pharmacokinetic (PK) measurements of secukinumab 
will be included in the pharmacokinetic 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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9.6.13 
Pharmacokinetics  
Exploratory analysis to investigate the relationship between the PK data and efficacy outcomes 
will be performed. 
9.8 
Sample size calculation 
A response rate of 8% for PASI 75 response and IGA mod 2011 0 or 1 response in the placebo 
group is expected, whereas a response rate of 62% for PASI 75 response and 55% for IGA mod 
2011 0 or 1 is the anticipated response in the secukinumab 300 mg 2 mL pre-filled syringe 
group. 
Placebo-response rates between 3% and 7% have been reported in Papp et al 2005, Menter et 
al 2008, Leonardi et al 2008, and Papp et al 2008. 
9.8.1 
Primary endpoint (co-primary endpoint): 
With respect to the co-primary endpoint (PASI 75 response and IGA mod 2011 0 or 1 response 
at Week 12), the type-I-error will be 2.5% one-sided for comparison. With 70 subjects per group 
and assuming a response rate of 10% for PASI 75 response and IGA mod 2011 0 or 1 response 
in the placebo group, the power to show a response rate of 62% for PASI 75 response and 55% 
for IGA mod 2011 0 or 1 response in the secukinumab 300 mg 2 mL pre-filled group based on 
Fisher’s exact test (nQuery Advisor 6.01, two group Fisher’s-exact test of equal proportions) is 
above 99% for PASI 75 response and IGA mod 2011 0 or 1 response. 
9.8.2 
Secondary endpoints(s): 
A power of 90% to show a response rate of 30% for PASI 100 in the secukinumab 300 mg 2 mL 
pre-filled group and 8% in the placebo group based on Fisher’s exact test results in a sample 
size of 70 subjects per group. Same power can be achieved if we apply the same assumption of 
PASI 100 response rate for secukinumab 300 mg 1 mL pre-filled group. 
A power of above 99% to show a response rate of 46% for PASI 90 in the secukinumab 300 mg 
2 mL pre-filled group and 8% in the placebo group based on Fisher’s exact test results in a 
sample size of 70 subjects per group. 


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10 
Ethical considerations  
10.1 
Regulatory and ethical compliance  
This clinical study was designed and shall be implemented, executed 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 CFR 21, and Japanese 
Ministry of Health, Labor, and Welfare), and with the ethical principles laid down in the 
Declaration of Helsinki. 
10.2 
Informed consent procedures  
Eligible subjects may only be included in the study after providing (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(s) of the subject. In cases 
where the subject’s representative gives consent, the subject must be informed about the study 
to the extent possible given his/her understanding. If the subject is capable of doing so, he/she 
must indicate assent by personally signing and dating the informed consent document or a 
separate assent form. Informed consent must be obtained before conducting any study-specific 
procedures (e.g. all of the procedures described in the protocol). The process of obtaining 
informed consent must be documented in the subject 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 Informed 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 
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion from 
the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial protocol, 
written Informed Consent Form, consent form updates, subject recruitment procedures (e.g., 
advertisements) and any other written information to be provided to subjects. 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 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 
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. 


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11 
Protocol adherence  
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of subjects should be 
administered as deemed necessary on a case by case basis. Under no circumstances is an 
investigator allowed to collect additional data or conduct any additional procedures for any 
research related purpose involving any investigational drugs under the protocol. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and health authorities, where required, it cannot be implemented.  
11.1 
Protocol amendments  
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation, where required. Only amendments that are intended to eliminate an apparent 
immediate hazard to subjects may be implemented immediately provided the health authorities 
are subsequently notified by protocol amendment and the reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any subject included in this 
study, even if this action represents a deviation from the protocol. In such cases, the reporting 
requirements identified in Section 7 Safety Monitoring must be followed.                       
   


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12 
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[Chobanian AV, Bakris GL, Black HR (2003)] Seventh report of the joint national committee 
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[Doherty SD, Van Voohees A, Lebwohl MG (2008)] National psoriasis foundation consensus 
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[Keininger D, Coteur G (2011)] Assessment of self-injection experience in patients 
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[Kerdel F, Zaiac M (2015)] An evolution in switching therapy for psoriasis patients who fail 
to meet treatment goals. Dermatol Ther; Epub ahead of print. 
[Kimball, AB, Gordon, KB, Fakharzadeh, S, et al. (2012)] Long-term efficacy of ustekinumab 
in patients with moderate-to-severe psoriasis: results from the PHOENIX 1 trial through up to 
3 years. Br. J. Dermatol. 166: 961-72. 
[Langley RG, Elewski BE, Lebwohl M, et al. (2014)] Secukinumab in plaque psoriasis – 
results of two phase 3 trials. N Engl J Med; 371: 326-38. 
[Leonardi CL, Kimball AB, Papp KA, et al. (2008)] Efficacy and safety of ustekinumab, a 
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from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet; 371: 1665-
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[Mancia G, De Backer G, Dominiczak A, et al. (2007)] Guidelines for the Management of 
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European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J 
Hypertens; 25: 1105-87.  
[Manuel O, Kumar D (2008)] QuantiFERON-TB Gold assay for the diagnosis of latent 
tuberculosis infection. Expert Rev Diagn; 8(3): 247-56. 
[Menter A, Gottlieb A, Feldman S, et al (2008)] Guidelines of care for the management of 
psoriasis and psoriatic arthritis – Section 1. Overview of psoriasis and guidelines of care for 
the treatment of psoriasis with biologics. J Am Acad Dermatol; 58: 826-50. 
[Newcombe RG (1998)] Two-sided confidence intervals for the single proportion: comparison 
of seven methods. Statistics in Medicine; 17: 857-72. 
NIH Clinical Center Patient Education Materials: giving a subcutaneous injection; 2012. 
Novartis Investigator’s Brochure (2015) Secukinumab, Edition 15. 
[Papp KA, Tyring S, Lahfa M, et al (2005)] A global phase II randomized controlled trial of 
etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol; 152: 
1304-12. 
[Papp KA, Langley RG, Lebwohl M, et al. (2008)] Efficacy and safety of ustekinumab, a 
human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results 
from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet; 371: 1675-
84. 
[Paul C et al (2015)] Efficacy, safety and usability of secukinumab administration by 
autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad 
Dermatol Venereol; 29: 1082-90. 
[Puig L (2014)] PASI 90 response: the new standard in the therapeutic efficacy for psoriasis. J 
Eur Acad Dermatol Venereol; 29: 645-48. 
[Thaci D, Blauvelt A, Reich K, et al. (2015)] Secukinumab is superior to ustekinumab in 
clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized 
controlled trial. J Am Acad Dermatol; 73: 400-9. 


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The Rules Governing Medicinal Products in the EU: Detailed guidance on the collection, 
verification and presentation of adverse event/reaction reports arising from clinical trials on 
medicinal products for human use (2011/C 172/01), June 2011. 
[Van Lümig, PP, Lecluse, LL, Driessen, RJ, et al, (2010)] Switching from etanercept to 
adalimumab is effective and safe: results in 30 patients with psoriasis with primary failure, 
secondary failure or intolerance to etanercept. Br J Dermatol.; 163: 838-46. 
[Weisman S, Pollack CR, Gottschalk RW (2003)] Psoriasis disease severity measures: 
comparing efficacy of treatments for severe psoriasis. J Dermatolog Treat; 14: 158-65. 


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13 
Appendix 1: Clinically notable laboratory values and vital 
signs 
The following criteria will be used to define expanded limits and notable abnormalities of key 
laboratory tests. Notable values for blood pressure and pulse are presented in Section 6.5.2. 
No specific action is pre-defined within this protocol to respond to specific abnormal laboratory 
values, as it will be decided by the investigator whether and which specific action needs to be 
taken to respond to any abnormal values, taking into account the overall status of the subject. 
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  
Creatinine (serum): 
 
 
 
> 1.5 x ULN 
Hematology Variables 
Hemoglobin:  
 
 
 
≥ 20 g/dL decrease from baseline 
Platelet count:  
 
 
 
< Lower Limit of Normal (LLN) 
White blood cell count: 
 
 
< 0.8 x LLN 
Neutrophils:  
 
 
 
< 0.9 x LLN 
Eosinophils:  
 
 
 
> 1.1 x ULN 
Lymphocytes:  
 
 
 
> 1.1 x ULN 
Urinalysis Variable 
Protein urine dipstick:  
 
 
++* 
* ++ is ≥ 100 mg/dL 


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Appendix 2: Blood collection log for pharmacokinetics 
 
  
Table 14-1 
Blood collection log for pharmacokinetics 
Visit/Week 
Timepoint 
Volume 
Analysis 
Sample 
number*** 
PK collection 
number 
/Dose 
Reference ID 
Randomization 
Pre-dose 
2 mL 
AIN457 for PK 
1 
1 
Week 4 
Pre-dose 
2 mL 
AIN457 for PK 
2 
2 
Week 12/EOTEI 
Pre-dose 
2 mL 
AIN457 for PK 
3 
3 
Week 13 
168 h (post-dose)* 
2 mL 
AIN457 for PK 
4 
3 
Week 14 
336 h (post-dose)* 
2 mL 
AIN457 for PK 
5 
3 
Week 15 
504 h (post-dose)* 
2 mL 
AIN457 for PK 
6 
3 
Week 16 
672 h (post-dose)* 
2 mL 
AIN457 for PK 
7 
3 
Week 28 
Pre-dose 
2 mL 
AIN457 for PK 
8 
4 
Week 52/EOTEII 
672 hours** 
2 mL 
AIN457 for PK 
9 
5 
*Post–dose timepoints refer to the dose administered at Week12. PK samples should be drawn before 
dose/placebo administration at Weeks 13, 14, 15, 16. 
**Scheduled post-dose time point for sample number 9 (672 hours post-dose) referred to the last dose given at 
week 48. 
*** If a PK sample is collected at an unscheduled visit, sample numbers will follow the pattern, 1001, 1002, etc. 
Note: all blood samples should be taken prior to dosing  
 


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15 
Appendix 3: Scoring of the SIAQ 
The scoring of domains is performed in 2 steps: 
1. The raw item scores ranging from 1 to 5 are transformed into scores ranging from 0 (worst 
experience) to 10 (best experience). 
2. The transformed scores for items contributing to a domain are then averaged into a 
domain score. 
Table 15-1 
Scoring of domains from raw item scores 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Items 
Transformed item score 
Domain score 
calculation 
Domain score 
range 
PRE module domain 
FL 
1-3 
((raw score)-1)*2.5 
Average of 
transformed item 
scores 
0-10 
CO 
4-6 
((raw score)-1)*2.5 
SA 
7 
((raw score)-1)*2.5 
POST module domain 
FL 
1-3 
((raw score)-1)*2.5 
Average of 
transformed item 
scores 
0-10 
IM 
4 
((raw score)-1)*2.5 
CO 
5-7 
((raw score)-1)*2.5 
RE 
8-9 
((raw score)-1)*2.5 
EU 
10-14 
((raw score)-1)*2 
SA 
15-21 
((raw score)-1)*2.5 


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Appendix 4: SIAQ Questionnaire  
 
- Representative example –  
 
 
 
 
 
 
 


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SIAQ (Pre-Self-Injection, continued) 
 
 
 
 
 
 
 
 
 
 
 


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Appendix 5: DLQI Questionnaire 
 
 
 
 


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SAP_000.pdf: 
Clinical Development 
AIN457/ Secukinumab/Cosentyx® 
CAIN457A2323 / NCT02748863
A multicenter, randomized, double-blind, placebo-
controlled, 52-weeks study to demonstrate the efficacy, 
safety and tolerability of subcutaneous secukimumAb 
injections with 2 mL pre-fiLLed syringes (300 mg) in adUlt 
subjects with moderate to seveRE plaque psoriasis 
(ALLURE) 
Statistical Analysis Plan (SAP) 
Author: 
Statistician,  
 
Document type: 
SAP Documentation 
Document status: 
Addendum 1.0 
Release date: 
11 Sep 2018 
Number of pages: 
58 
Property of Novartis 
For business use only 
May not be used, divulged, published or otherwise disclosed 
without the consent of Novartis 


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Table of contents 
Table of contents ................................................................................................................. 3 
List of abbreviations ............................................................................................................ 5 
1 
Introduction ......................................................................................................................... 7 
1.1 
Study design............................................................................................................. 7 
1.2 
Study objectives and endpoints ............................................................................... 8 
2 
Statistical methods ............................................................................................................... 9 
2.1 
Data analysis general information ........................................................................... 9 
2.1.1 
General definitions ................................................................................ 10 
2.2 
Analysis sets .......................................................................................................... 11 
2.2.1 
Subgroup of interest .............................................................................. 12 
2.3 
Patient disposition, demographics and other baseline characteristics ................... 12 
2.3.1 
Patient disposition ................................................................................. 13 
2.4 
Treatments (study treatment, concomitant therapies, compliance) ....................... 13 
2.4.1 
Study treatment / compliance ................................................................ 13 
2.4.2 
Prior, concomitant and post therapies ................................................... 16 
2.5 
Analysis of the primary objective .......................................................................... 18 
2.5.1 
Primary endpoint ................................................................................... 18 
2.5.2 
Statistical hypothesis, model, and method of analysis .......................... 22 
2.5.3 
Handling of missing values/censoring/discontinuations ....................... 23 
2.5.4 
Supportive analyses ............................................................................... 24 
2.6 
Analysis of the key secondary objective ............................................................... 24 
2.6.1 
Key secondary endpoint ........................................................................ 24 
2.6.2 
Statistical hypothesis, model, and method of analysis .......................... 24 
2.6.3 
Handling of missing values/censoring/discontinuations ....................... 25 
2.7 
Analysis of secondary efficacy objective(s) .......................................................... 25 
2.7.1 
Secondary endpoints ............................................................................. 25 
2.7.2 
Statistical hypothesis, model, and method of analysis .......................... 26 
2.7.3 
Handling of missing values/censoring/discontinuations ....................... 26 
2.8 
Safety analyses ....................................................................................................... 26 
2.8.1 
Adverse events (AEs) ............................................................................ 27 
2.8.2 
Deaths .................................................................................................... 29 
2.8.3 
Laboratory data ..................................................................................... 29 
2.8.4 
Other safety data ................................................................................... 32 
2.9 
Pharmacokinetics ................................................................................................... 32 
 
 33 


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2.11 
Clinician-reported outcomes .................................................................................. 33 
2.11.1 
Usability and hazard assessment of the 2 mL pre-filled syringe .......... 33 
2.12 
Patient-reported outcomes ..................................................................................... 34 
 
 35 
 
 35 
 
 36 
3 
Sample size calculation ..................................................................................................... 36 
3.1 
Primary endpoint (co-primary endpoint) ............................................................... 37 
3.1.1 
Secondary endpoints ............................................................................. 37 
4 
Change to protocol specified analyses .............................................................................. 37 
5 
Appendix ........................................................................................................................... 37 
5.1 
Imputation rules ..................................................................................................... 37 
5.1.1 
Study drug ............................................................................................. 37 
5.1.2 
AE date imputation ............................................................................... 38 
5.1.3 
Concomitant medication date imputation ............................................. 39 
5.1.4 
First diagnosis date (PsO, PsA) imputation .......................................... 40 
5.1.5 
Other imputations .................................................................................. 41 
5.2 
AEs coding/grading ............................................................................................... 41 
5.3 
Laboratory parameters derivations ........................................................................ 41 
5.4 
Statistical models ................................................................................................... 41 
5.4.1 
Analysis of continuous data .................................................................. 41 
5.4.2 
Analysis of binary (and categorical) data .............................................. 42 
5.4.3 
Logistic regression ................................................................................ 42 
5.4.4 
Multiple imputations for response variables ......................................... 43 
5.4.5 
Crude incidence and related risk estimates ........................................... 46 
5.4.6 
Exposure adjusted incidence rate and related risk estimates ................ 48 
5.5 
Rule of exclusion criteria of analysis sets.............................................................. 49 
5.6 
Clinician reported outcomes .................................................................................. 49 
5.6.1 
Usability and hazard assessment of the 2 mL pre-filled syringe .......... 49 
5.7 
Patient reported outcomes ...................................................................................... 51 
5.7.1 
Dermatology Life Quality Index (DLQI) .............................................. 51 
 
 52 
5.7.3 
Self-injection Assessment Questionnaire (SIAQ) ................................. 54 
6 
Reference ........................................................................................................................... 56 


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List of abbreviations 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase/glutamic pyruvic transaminase/GPT 
AST 
Aspartate aminotransferase/glutamic oxaloacetic transaminase/GOT 
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 
DAR 
Dosage Administration Record  
DLQI 
Dermatology Life Quality Index 
ECG 
Electrocardiogram 
eCRF 
Electronic case report/record form 
FAS 
Full analysis set 
FDA 
United States Food and Drug Administration 
GGT 
Gamma-glutamyl transferase 
HGB 
Hemoglobin 
IFU 
IGA 
Instructions For use 
Investigator’s global assessment 
IGA mod 2011 
Novartis Investigator’s Global Assessment modified 2011 
IRT 
Interactive response technology 
LLN 
Lower Limit of Normal 
LPLV 
Last patient’s last visit 
MACE 
Major Adverse Cardiovascular Event 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
NMQ 
Novartis MedDRA Query 
NovDTD 
Novartis Drug and Therapy Dictionary 
PASI 
Psoriasis Area and Severity Index 
PD 
PFS 
Protocol deviation 
Pre-filled syringe 
PT 
Preferred Term 
RMP 
Risk Management Plan 
S.C. 
SAS 
Subcutaneous 
Statistical analysis software 
SAE 
Serious adverse event 
SIAQ 
SPP 
Self-Injection Assessment Questionnaire 
Safety Profiling Plan 
SOC 
System Organ Class 
TBL 
Total bilirubin 
TEAE 
Treatment Emergent Adverse Event 
ULN 
Upper Limit of Normal 


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WBC 
White blood cell 


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1 
Introduction 
Data will be analyzed by Novartis 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. 
This document covers statistical and analytical plans for CAIN457A2323 (ALLURE) study 
with reference to the study protocol and the project standard analysis plans (AIN457A Master 
Analysis Plan). 
1.1 
Study design 
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in 
approximately 210 subjects with moderate to severe chronic plaque-type psoriasis. 
Randomization: Eligible subjects will be randomized using a 1:1:1 ratio into one of the three 
treatment groups below. Randomization will not be stratified. 
• Secukinumab 300 mg (2mL PFS): will receive one 2 mL secukinumab 300 mg plus two 
1 mL matching secukinumab placebo s.c. injections once weekly for four weeks (at 
Randomization, Weeks 1, 2 and 3), followed by dosing every four weeks, starting at Week 
4 up to Week 48. Subjects will receive three placebo injections at Weeks 13, 14 and 15. 
• Secukinumab 300 mg (2x1mL PFS): will receive two 1 mL secukinumab 150 mg plus 
one 2 mL matching secukinumab placebo s.c. injections once weekly for four weeks (at 
Randomization, Weeks 1, 2 and 3), followed by dosing every four weeks, starting at Week 
4 up to Week 48. Subjects will receive three placebo injections at Weeks 13, 14 and 15. 
• Placebo: will receive secukinumab placebo (two 1 mL and one 2 mL s.c. injections) once 
weekly for four weeks (at Randomization, Weeks 1, 2 and 3), followed by dosing every 
four weeks, starting at Week 4 up to Week 12 (pre-dose). 
Prior to receiving the Week 12 dose, all subjects from the placebo group will be assigned 
to the following treatment groups based on their PASI 90 response status as Week 12. 
• PASI 90 non-responders: will receive either one 2 mL 300 mg secukinumab s.c. plus 
two 1 mL matching placebo OR two 1 mL 150 mg secukinumab s.c. injections plus 
one 2 mL matching placebo, according to the pre-assignment at the Randomization 
visit using 1:1 ratio, at Weeks 12, 13, 14, 15 and then every four weeks starting at 
Week 16 up to Week 48; 
• PASI 90 responders: will continue on placebo (one 2 mL plus two 1 mL s.c. 
injections) and will receive their placebo injections at Weeks 12, 13, 14, 15 and then 
every four weeks starting at Week 16 up to Week 48. 
 
Of note: For PASI 90 non-responders in placebo group, pre-assigned treatment groups at 
Randomization visit will be used instead of re-randomization at Week 12, therefore eligible 
subjects will be randomized using pre-assigned 2:2:1:1 ratio into one of the four treatment 
groups at Randomization visit (similar to 1:1:1 for all subjects at Randomization visit with 1:1 
for PASI 90 non-responders in placebo group at Week 12). 
• Secukinumab 300 mg (2mL PFS) 


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• Secukinumab 300 mg (2x1mL PFS) 
• Placebo - Secukinumab 300 mg (2mL PFS) 
• Placebo - Secukinumab 300 mg (2x1mL PFS) 
 
The following study periods will be considered for analysis: 
• Screening period (before Randomization)  
• Treatment period 1 (Randomization to Week 12 pre-dose), including follow-up period 
(F4 and F8 visits) for prematurely discontinued subjects before Week 12 completion. 
• Treatment period 2 (Week 12 dose to Week 52), including follow-up period (F4 and 
F8 visits) for prematurely discontinued subjects before Week 52 completion. 
• Entire treatment period (Randomization to Week 52, last dose at Week 48), including 
follow-up period (F4 and F8 visits) for prematurely discontinued subjects. 
Of note: data from follow-up period (i.e., treatment free follow-up period after EOT visit, which 
includes F4 and F8 visits) for prematurely discontinued subjects will be included in the analysis 
of treatment period. 
 
 
1.2 
Study objectives and endpoints 
The primary objective of this study is to demonstrate the efficacy of secukinumab 300 mg when 
administered as 2 mL pre-filled syringes in subjects with plaque-type psoriasis with respect to 
both PASI 75 and IGA mod 2011 0 or 1 response rates at Week 12, compared to placebo. 
The key secondary objectives are  
1) to demonstrate the efficacy of secukinumab 300 mg when administered as 2 mL pre-
filled syringes versus placebo with respect to: 
• PASI 90 response at Week 12 
• PASI 100 response at Week 12 
2) to demonstrate the efficacy of secukinumab 300 mg when administered as two 1 mL 
pre-filled syringes versus placebo with respect to: 
• PASI 100 response at Week 12 
Furthermore, additional aspects of efficacy, safety and tolerability of secukinumab 300 mg as 
2 mL pre-filled syringes compared to secukinumab 300 mg as two 1 mL pre-filled syringes over 
a period of 52 weeks will be investigated. 
This study will provide efficacy and safety data to support a product labeling updates for the 
indication of moderate to severe plaque psoriasis. 


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Table 1-1 
Primary, key secondary, secondary and exploratory variables 
Variable 
Type 
PASI 75 response @ Week 12  
primary 
IGA 0/1  response @ Week 12  
primary 
PASI 90 response @ Week 12  
key secondary 
PASI 100 response @ Week 12 
key secondary 
PASI 50/75/90/100 and IGA 0/1 response over time  
secondary 
PASI score and IGA mod 2011 categories over time 
secondary 
Device usability (IFU and use-related hazards) 
secondary 
SIAQ 
secondary 
DLQI score 
secondary 
DLQI 0 or 1 achievement 
secondary 
2 
Statistical methods 
2.1 
Data analysis general information 
Novartis will be performing 
 final analysis. Statistical 
software SAS version 9.4 or later will be used. 
 
 
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. 
The p-values will be presented as one-sided for hypothesis testings and as two-sided for other 
analysis. Two-sided 95% confidence intervals will be displayed. If not otherwise specified, 
hypothesis testings will be based on one-sided p-values that the treatment effect is in favor of 
Secukinumab. The level of significance will be set to 2.5% (one-sided, family-wise type-I-error). 
The 95% confidence intervals will not be used for decision making; they will only be used for 
estimation and will therefore always be two-sided. 
All listings will be presented by treatment sequence. 
Footnotes on outputs will be kept to a minimum also for outputs not covered in [MAP TFL 
shells].  
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 


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• 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 than 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) 
2.1.1 
General definitions  
2.1.1.1 
Study treatment 
The following study drugs will be used: 
• Investigational treatment 
o Secukinumab 300 mg, 2 mL liquid formulation in a pre-filled syringe 
• Control treatment 
o Secukinumab 150 mg, 1 mL liquid formulation in a pre-filled syringe 
o Secukinumab placebo, 2 mL liquid formulation in a pre-filled syringe 
o Secukinumab placebo, 1 mL liquid formulation in a pre-filled syringe 
2.1.1.2 
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. 
2.1.1.3 
Screening, 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 (for safety analysis) or prior to the randomization 


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date (for efficacy analysis). 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. 
 
For efficacy analyses, baseline is the last assessment (including unscheduled visits) obtained 
(on or) before the randomization (day). All assessments obtained after randomization (day) are 
considered as post-baseline unless otherwise specified. 
For safety analyses, baseline is the last assessment (including unscheduled visits) obtained (on 
or) before the first dose (day) of study treatment. All assessments obtained after the first dose 
(day) of study treatment 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, LAB assessments and ECG if no pre-
treatment value exists, values obtained after first dose of treatment can be used as baseline only 
if it was collected on the same day as first dose. 
2.1.1.4 
Day of last dose of randomized study treatment 
The date of last dose will be collected via the CRF.  
Duration of exposure is defined in Section 2.4.1. 
On-treatment is defined as assessments within last dose plus 84 days. 
2.2 
Analysis sets 
The following analysis sets will be used for the data analysis.  
Randomized set: The randomized set will be defined as all subjects who were randomized at 
baseline visit. Unless otherwise specified, mis-randomized subjects will be excluded from the 
randomized set. 
Misrandomized subjects are subjects who are screen-failures, but have been randomized by the 
investigator before eligibility was finally assessed, however have not been treated. If previously 
mis-randomized subjects were re-screened and successfully randomized, they will be included 
in the randomized set according to the treatment assigned in the last randomization.  
Full analysis set (FAS): The FAS will be comprised of all subjects from the randomized set to 
whom study treatment has been assigned. Following the intent-to-treat principle, subjects will 
be analyzed according to the treatment assigned to at randomization. If the actual randomization 
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. 
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.  
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.  


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For those subjects who received erroneously the wrong treatment at least once, an additional 
listing will be prepared displaying adverse events occurred after the treatment errors. 
2.2.1 
Subgroup of interest 
Not applicable. 
2.3 
Patient disposition, demographics and other baseline 
characteristics 
The summaries will be shown for the following treatment groups, 
before or at Week 12: 
• AIN457 300 mg (2mL PFS), AIN457 300 mg (2x1mL PFS), Placebo, Total 
after Week 12: 
• AIN457 300 mg (2mL PFS), AIN457 300 mg (2x1mL PFS), Placebo, Placebo - 
AIN457 300 mg (2mL PFS), Placebo - AIN457 300 mg (2x1mL PFS), Total 
No summaries for entire treatment period will be provided. 
The following common background and demographic variables will be analyzed: 
Continuous variables: 
o Age (which is derived from year of birth and the Informed consent date, 
assuming date is July 1st since only year of birth is collected) 
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 Sex 
o Race 
o Ethnicity 
o Smoking status at baseline 
Psoriasis specific baseline characteristics and history of disease will be summarized as well: 
baseline PASI, baseline PASI (≤20, >20), baseline total BSA, baseline IGA mod 2011 score (at 
least mild, moderate, severe), severity of psoriasis (CHMP guidelines, mild (total BSA <10% 
and PASI < 10), moderate ((PASI ≥10 or total BSA≥10%) and PASI ≤20 and total BSA ≤20%), 
severe (total BSA >20% or PASI > 20)), psoriatic arthritis (yes, no), 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 (including phototherapy and photo-chemotherapy) 
Body Mass Index (BMI) will be calculated using the following formula: 
BMI = (body weight in kilograms) / (height in meters)2 


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For BMI, height and body weight the last value prior to randomization is used. If there is no 
weight recorded prior to taking of study treatment, BMI will be missing. 
Of note: subject’s height will not be remapped according to the analysis visit window. 
Time since diagnosis of psoriasis (PsO) and time since diagnosis of psoriatic arthritis (PsA) will 
be calculated using the following formula: 
Time since diagnosis = (inform consent date –first diagnosis date + 1)/365.25 
The first diagnosis date of PsO or PsA will be imputed according to the imputation rules in 
Section 5.1. 
Unless otherwise specified, summary statistics will be presented for continuous variables for 
each treatment group and for all subjects (total) 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 (total) in the randomized set. 
Any condition entered on the relevant medical history / current medical conditions CRF 
(including family history) will be coded using the MedDRA dictionary. They will be 
summarized by System Organ Class (SOC) and Preferred Term (PT) of the MedDRA dictionary. 
Summaries for cardiovascular medical history will be summarized by categories.  
Smoking history will be summarized by treatment group. 
Unless otherwise specified, analyses will be based on the randomized set. 
2.3.1 
Patient disposition 
The number of subjects screened will be presented. In addition, the reasons for screen failures 
will be provided. The number and percentage of subjects in the randomized set who completed 
study periods and who discontinued the study prematurely (including the reason for 
discontinuation) will be presented for each treatment group and all subjects. 
For each protocol deviation, the number and percentage of subjects for whom the deviation 
applies will be tabulated. 
2.4 
Treatments (study treatment, concomitant therapies, 
compliance) 
2.4.1 
Study treatment / compliance 
The analysis of study treatment data will be based on the safety set. 
The number of secukinumab 2mL syringes, 1mL secukinumab syringe, secukinumab placebo 
injections will be summarized by treatment group by means of contingency tables. 
The duration of exposure to study treatment will be summarized by treatment group. In addition, 
the number of subjects with exposure of at least certain time thresholds will be displayed. The 
following categories will be presented: “any exposure”, “≥1 week”, “≥2 week”, “≥3 week”, “≥4 
weeks”, “≥8 week”, “≥12 weeks”, “≥16 weeks”, “≥28 weeks”, “≥40 weeks” and “≥52 weeks”. 


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Duration of exposure will be defined as the time from first dose of study medication to the last 
dose plus 84 days or last visit (including follow-up visits) whichever occurs earlier. i.e., for 
subjects who discontinued or have their last visit earlier than 84 days, the end of study treatment 
exposure will be the date of the last study visit in the follow-up period or in the corresponding 
treatment period. 
Duration of exposure (days) = min (last study visit (including follow-up) date, last dose date 
+84) – first dose date +1 
Duration of exposure (years) = duration of exposure (days) / 365.25 
Duration of exposure (100 subject years) = duration of exposure (years) / 100 
 
 
2.4.1.1 
Visit window 
Visit-windows will be used for the data that is summarized by 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 2-1. 
In this table, the days are counted since the first dose of study treatment ( Day 1) 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.  
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 60 instead 
of on Day 29, 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. 
For parameters which are not collected at every visit (e.g., DLQI), visit windows will be 
combined. For example, if a parameter is measured at Week 12 and Week 28 only, Week 12 
visit window will extend from Day 2 to Day 99 (combining Week 1 to Week 12 visit windows), 
and Week 28 will be extend from Day 100 to Day 239. 
Assessments from treatment period 2 will not be considered for treatment period 1, and 
treatment period 1 visits will not be mapped into treatment period 2. 
Of note: for subjects who prematurely discontinued, efficacy measurements taken in follow-up 
period will be remapped to treatment periods. 


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Table 2-1 
Assessment windows for scheduled visits  
Analysis Visit 
Week 
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 100-155 
Week 28 
28 
197 
Day 156-239 
Week 40 
40 
281 
Day 240-323 
Week 52 
52 
365 
Day 324-421 
* Baseline measurement before the first drug administration for safety assessments and before the randomization 
for efficacy assessments. 
Of note: subject’s height will not be remapped according to the analysis visit window. 
The analysis visit will be used for listing of visit and period for safety data. If a visit falls after 
the last visit window (after Day 421) it is not assigned an analysis visit and will be listed under 
label “After Week 52”. 
2.4.1.2 
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 
2-2). 
For baseline assessment definition see Section 2.1.1.3. 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 “++”), 
• in case qualitative variables are based on quantitative variables, e.g. PASI 90 response, the 
visit will be assigned to the quantitative variable, and this visit will be used for the derived 
qualitative variable.  


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Table 2-2 
Rules for selecting values for analysis within a given visit window 
Timing of measurement 
Type of data 
Rule 
Baseline 
All data 
See Section 2.1.1.3. 
Post-baseline efficacy 
All data except for PRO, e.g., 
PASI, IGA 
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 day then select the first one using 
eCRF visit number. 
If two measurements have been taken on 
the same day and same visit then select 
the worst. 
Post-baseline efficacy 
PRO data 
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 have been taken on 
the same day, select the worst. 
If two measurements have the same 
value, select the first one using eCRF visit 
number. 
Post-baseline safety 
Summary visit information 
(e.g. laboratory values, vital 
signs, etc.) 
The (non-missing) 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 day then select the first one (using 
the time). 
If two measurements are taken on the 
same date/time then use the first eCRF 
visit number (assuming this is the planned 
visit).If two measurements are taken on 
the same date/time/eCRF visit number 
then take the average value of these two 
results. 
Post-baseline safety  
Notable abnormalities (e.g. 
vitals signs) and CTCAE 
grades for laboratory values 
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 an 
analysis period. 
2.4.2 
Prior, concomitant and post therapies 
Medications will be identified using 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 unless otherwise specified. Concomitant 
treatments will be displayed for the treatment period 1 and entire treatment period. 


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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 the 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 visit (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.  
Summaries of prior and/or concomitant psoriasis specific medication will be presented as in 
Table 2-3, but as well for topical, phototherapy and photochemotherapy (yes/no) using the 
randomized set. 
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 Section 5. 


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Table 2-3 
Subgroups based on the previous psoriasis therapy 
Level 1 
description 
Level 1 
outcome 
Level 2 
description 
Level 2 
outcome 
Level 3 
description 
Level 3 
outcome 
Level 4 
description 
Level 4 
outcome 
previous 
therapy 
yes/no 
systemic 
no 
yes 
number 
1 
2 
>=3 
failure* 
no 
yes 
biologic 
no 
yes 
failure* 
no 
yes 
type of previous biologic 
anti-p40 
no 
yes 
failure* 
no 
yes 
anti-TNF 
no 
yes 
failure* 
no 
yes 
lack of primary 
efficacy 
no 
yes 
lack of secondary 
efficacy 
no 
yes 
lack of primary or 
secondary efficacy 
no 
yes 
lack of tolerability 
no 
yes 
non-biologic 
systemic 
no 
yes 
failure* 
no 
yes 
failure* to at 
least 2 
no 
yes 
only selected subgroups will be used for reporting 
*: at least one therapy with lack of primary efficacy or lack of secondary efficacy or lack of tolerability 
2.5 
Analysis of the primary objective 
2.5.1 
Primary endpoint 
The co-primary endpoints are PASI 75 response and IGA 0 or 1 response at Week 12. The 
analysis of the primary variables will be based on the FAS. 
2.5.1.1 
Definition of PASI and related variables 
The investigator or trained qualified designee will complete the PASI assessments. Whenever 
possible, the same evaluator should perform this assessment at all visits. 
The total BSA affected by plaque-type psoriasis will be estimated from the percentages of areas 
affected, including head, trunk, upper limbs and lower limbs (see below for PASI assessment). 
The following calculations will be done: each reported percentage will be multiplied by its 
respective body region corresponding factor (head = 0.1, trunk = 0.3, upper limbs = 0.2, lower 


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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 2-4. 
A PASI score (Fredriksson and Pettersson 1978, Weisman et al 2003, Gottlieb et al 2005) will 
be derived as indicated in Table 2-4. The head, trunk, upper limbs and lower limbs are assessed 
separately for erythema, thickening (plaque elevation, induration), and scaling (desquamation). 
The average degree of severity of each sign in each of the 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 will be 
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 
2-4). 
PASI scores can range from a lower value of 0, corresponding to no signs of psoriasis, up to a 
theoretic maximum of 72.0. 
The investigator is responsible for collecting the components or scoring signs and total regional 
area for all visits. Total PASI and total BSA calculations will be done by investigator at 
screening and randomization only; The total PASI and BSA scores will be calculated by 
Novartis and will be used in the analysis and for derivation of PASI response values (see below).  


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Table 2-4 
The PASI scoring system 
Body  
region 
Erythema (E) 
 
Thickening 
(plaque elevation, 
induration, I) 
Scaling  
(desquamation, 
D) 
Area score 
(based on true 
area %, A)* 
Head (H)† 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0 = no involvement 
1 = >0-<10% 
2 = 10-<30% 
3 = 30-<50% 
4 = 50-<70% 
5 = 70-<90% 
6 = 90-100% 
Trunk (T)‡ 
0=none  
1=slight  
2=moderate 
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0 = no involvement 
1 = >0-<10% 
2 = 10-<30% 
3 = 30-<50% 
4 = 50-<70% 
5 = 70-<90% 
6 = 90-100% 
Upper  
limbs (U) 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0 = no involvement 
1 = >0-<10% 
2 = 10-<30% 
3 = 30-<50% 
4 = 50-<70% 
5 = 70-<90% 
6 = 90-100% 
Lower  
limbs (L)§ 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0 = no involvement 
1 = >0-<10% 
2 = 10-<30% 
3 = 30-<50% 
4 = 50-<70% 
5 = 70-<90% 
6 = 90-100% 
* 
Percentage (not score) of body region (not whole body) affected will be entered in the eCRF. 
† 
Neck is assessed as part of the Head (H) body region. 
‡ 
Axillae and groin are assessed as part of the Trunk (T) body region. 
§ 
Buttocks are assessed as part of the Lower limbs (L) body region. 
 
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 
• PASI 100 response / remission: complete clearing of psoriasis (PASI=0) 
• 
 
  


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2.5.1.2 
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 2-5) 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. It is recommended that the same evaluator conducts the 
assessments throughout the study whenever possible. 
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 2-5 
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. 
Subjects require an IGA mod 2011 score at randomization of 3 or 4 in order to participate in 
the study. 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 mod 2011 scale 
compared to baseline. 
2.5.1.3 
Overview of analysis methods of efficacy variables 
An overview of statistical analyses and methods applied to psoriasis efficacy variables is given 
in Table 2-6. 


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Table 2-6 
Overview of analysis methods for efficacy variables 
Variable(s) 
Summary 
statistics for 
binary/ 
categorical data  
Logistic 
regression 
Summary 
statistics for 
continuous 
data 
Time-to-
event 
analysis 
Graphs 
PASI 75 response @ Week 12 
X 
X 
 
 
X* 
IGA 0/1 response @ Week 12 
X 
X 
 
 
X* 
PASI 90 response @ Week 12 
X 
X 
 
 
X* 
PASI 100 response @ Week 12 
X 
X 
 
 
X* 
PASI 50/75/90/100 and IGA 0/1 response 
over time 
X 
X 
 
 
X** 
PASI score over time 
 
 
X 
 
X** 
IGA mod 2011 categories over time 
X 
 
 
 
 
Device usability (IFU and use-related 
hazards) 
X 
 
 
 
 
SIAQ 
 
 
X 
 
 
DLQI score over time 
 
 
X 
 
 
DLQI 0/1 over time 
X 
 
 
 
 
* dot plot; ** time course plot 
2.5.2 
Statistical hypothesis, model, and method of analysis 
The statistical hypotheses are that secukinumab 300 mg (2mL PFS) is not superior to placebo 
in the proportion of subjects with PASI 75 response and IGA 0 or 1 response at Week 12. 
Let pj denote the proportion of PASI 75 responders at Week 12 for treatment group j and rj 
denote the proportion of IGA 0 or 1 responders at Week 12 for treatment group j;  
j=0, 1, where  
• 0 corresponds to placebo, 
• 1 corresponds to secukinumab 300 mg (2mL PFS). 
The following hypotheses will be tested: 
    
H: H1∪H2 versus HA: HA1∩HA2 
H1: p1 – p0 ≤ 0 versus HA1: p1 – p0 > 0, 
    
H2: r1 – r0 ≤ 0 versus HA2: r1 – r0 > 0 
In other words: 
H: secukinumab 300 mg (2mL PFS) is not superior to placebo with respect to either PASI 75 
response at Week 12 or IGA 0 or 1 response at Week 12 or both 
H1: secukinumab 300 mg (2mL PFS) is not superior to placebo with respect to PASI 75 
response at Week 12 
H2: secukinumab 300 mg (2mL PFS) is not superior to placebo with respect to IGA 0 or 1 
response at Week 12 
The primary analysis method for PASI 75 and IGA 0 or 1 response at Week 12 will be evaluated 
using logistic regression model with treatment group, baseline bodyweight and baseline PASI 
score as explanatory variables (see Section 5 Appendix). Odds ratios will be computed for 


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comparisons of secukinumab dose regimen versus placebo utilizing the logistic regression 
model fitted. In case of the logistic regression does not converge due to low response rates in 
the placebo group, an exact logistic regression will be performed. In case of response rates of 
0% or 100% in one of the treatment groups, for analyses with multiple imputation, confidence 
intervals for risk difference and p-values from the t-test for the risk difference comparing to 0 
will be provided; for analyses with non-responder imputation, Fisher’s exact test will be 
performed and confidence intervals for risk difference will be provided. 
The hypotheses H1 and H2 will both be tested at α level = 2.5% (one-sided) and significant 
results will only be achieved if both hypotheses are rejected (i.e., if only one hypothesis is 
rejected and the other hypothesis is not rejected, superiority of secukinumab 300 mg 2mL PFS 
cannot be demonstrated). 
The primary analysis set will be the FAS. 
Summary statistics and figures will be provided as described in Section 5.4.2. Details in 
sensitivity analysis are provided in Section 2.5.4. 
2.5.3 
Handling of missing values/censoring/discontinuations 
Response variables based on PASI score and IGA mod 2011 categories will be imputed with 
multiple imputation (MI) as primary imputation method for the missing values. 
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 or IGA mod 2011 
categories will be imputed 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. 
(Modified) Non-responder imputation will be used as a sensitivity method: Missing values with 
respect to response variables based on PASI score and IGA 2011 categories will be imputed 
with non-response regardless to the reason for missing data (e.g. premature study 
discontinuation, missed visit, administrative issues), exceptions will apply to the following: 
• If a subject dropped out of the study prior to last scheduled visit and being responder 
consecutively at least for two preceding visits before drop-off, the subject will be 
imputed as responder for all the later visits till last scheduled visit. 
• If a subject who was responder at visit x-1 and visit x+1 but has missing data at visit x, 
then the subject will be imputed as responder for visit x as long as the distance between 
the scheduled visits x-1 and x is 4 weeks or less, and the distance between the scheduled 
visits x and x+1 is 4 weeks or less. Otherwise missing data will be imputed with non-
response. 
Summary tables for PASI scores and IGA mod 2011 categories will be imputed using MI. The 
mean for PASI score and the number (%) for IGA mod 2011 categories as well as their 95% 
confidence intervals will be given. In addition, PASI scores and IGA mod 2011 categories based 
on LOCF imputation will be provided in summary tables and listings. 


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Note: Only PASI and IGA mod 2011 based response variables are imputed with multiple 
imputation or non-response, other response variables (e.g. DLQI 0 or 1 achievement) will be 
imputed with LOCF. 
2.5.4 
Supportive analyses 
Sensitivity analyses will be performed as follows: 
(A) Co-primary endpoints (PASI 75 and IGA 0 or 1 response at Week 12) and key secondary 
endpoints will be evaluated using the  logistic regression as described in primary analysis 
method with non-responder imputations instead of multiple imputation for missing values.  
2.6 
Analysis of the key secondary objective 
2.6.1 
Key secondary endpoint 
The key secondary endpoints of this study are planned as follow: 
• PASI 90 response at Week 12 
• PASI 100 response at Week 12 
The null hypotheses for secondary objectives are as follows: 
o H3: secukinumab 300 mg (2mL PFS) is not superior to placebo with respect to PASI 
90 response at Week 12 
o H4: secukinumab 300 mg (2mL PFS) is not superior to placebo with respect to PASI 
100 response at Week 12 
o H5: secukinumab 300 mg (2x1mL PFS) is not superior to placebo with respect to PASI 
100 response at Week 12 
2.6.2 
Statistical hypothesis, model, and method of analysis 
The following hypotheses will be tested sequentially and are included in the hierarchical testing 
strategy and type-I-error will be set such that a family-wise type-I-error of α = 2.5% (one-sided) 
is kept. The graphical approach of (Bretz et al. 2009) for sequentially rejective testing 
procedures is used to illustrate the testing strategy: 


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Figure 1-1 
Testing strategy 
 
The secondary efficacy variables involved in the above testing strategy will be analyzed 
analogously to the primary endpoints. i.e., logistic regression model with treatment group, 
baseline bodyweight, and baseline PASI score as explanatory variables. Odds ratios will be 
computed for comparisons of secukinumab regimen versus placebo utilizing the logistic 
regression model fitted. 
The testing sequence will continue to H3 at α (one-sided) only if both H1 and H2 have been 
rejected at α (one-sided). Similarly, the testing sequence will continue to H4 at α (one-sided) 
only if H3 testing has been rejected. In case, H4 has been rejected at α (one-sided), the 
corresponding alpha (α) will be passed to the next hypotheses corresponding H5. 
2.6.3 
Handling of missing values/censoring/discontinuations 
See Section 2.5.3. 
2.7 
Analysis of secondary efficacy objective(s) 
2.7.1 
Secondary endpoints 
PASI 50, PASI 75, PASI 90, PASI 100, and IGA mod 2011 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 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).  
For PASI 50, PASI 75, PASI 90, PASI 100, and IGA mod 2011 0 or 1 response at each visit, 
up to Week 12, secukinumab dose regimen will be compared to placebo by means of logistic 
regression model with treatment group, baseline bodyweight and baseline PASI as effects. 
For PASI 50, PASI 75, PASI 90, PASI 100, and IGA mod 2011 0 or 1 response, the placebo 
adjusted response rates (i.e., risk difference) including 95% confidence interval (based on 
normal approximation) will be derived by visit, up to Week 12. In addition, Fisher’s exact test 


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will be applied to the treatment group comparisons between secukinumab dose regimens versus 
placebo. 
Figures will be provided for PASI 50, PASI 75, PASI 90, PASI 100, and IGA mod 2011 0 or 1 
response over time, by displaying estimates for response rates by treatment including 95% 
confidence intervals. 
PASI score and IGA mod 2011 categories over time 
Summary statistics will be provided for absolute PASI scores and IGA mod 2011 categories, as 
well as for percentage change from baseline for PASI scores by visit and treatment group. 
Figure will be provided for percentage changes in PASI scores over time. 
2.7.2 
Statistical hypothesis, model, and method of analysis 
Not applicable. 
2.7.3 
Handling of missing values/censoring/discontinuations 
See Section 2.5.3. 
2.8 
Safety analyses 
All safety analyses will be based on the safety set. Only those scheduled visits which were pre-
planned in the protocol will be reported in tables and figures for safety variables. 
Treatment groups for evaluation of entire treatment 
The summaries of evaluation will be reported for treatment period 1 and entire treatment period, 
respectively. 
 
 
The following groups will be used for treatment period 1: 
• AIN457 300 mg (2mL PFS): all subjects who are randomized to 300 mg 2mL PFS 
group at Randomization visit 
• AIN457 300 mg (2x1mL PFS): all subjects who are randomized to 300 mg 2x1mL 
PFS group at Randomization visit 
• Placebo: all subjects who are randomized placebo group at Randomization visit 
• Any AIN457 300 mg: Any AIN457 300 mg of (2mL PFS) or (2x1mL PFS) as above. 
The following groups will be used for entire treatment period: 
• AIN457 300 mg (2mL PFS): all subjects who are randomized to 300 mg 2mL PFS 
group at Randomization visit 
• AIN457 300 mg (2x1mL PFS): all subjects who are randomized to 300 mg 2x1mL 
PFS group at Randomization visit 
• Any AIN457 300 mg (2mL PFS): all subjects who are randomized to 300 mg 2mL 
PFS group at Randomization visit and all placebo subjects who are re-assigned to 300 
mg 2mL PFS at Week 12, but they are only considered after the treatment re-
assignment (Week 12 treatment injection). 


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• Any AIN457 300 mg (2x1mL PFS): all subjects who are randomized to 300 mg 
2x1mL PFS group at Randomization visit and all placebo subjects who are re-assigned 
to 300 mg 2x1mL PFS at Week 12, but they are only considered after the treatment re-
assignment (Week 12 treatment injection). 
• Placebo: all subjects who are re-assigned will only be considered until the re-
assignment point (Week 12 treatment injection). 
• Any AIN457 300 mg: Any AIN457 300 mg of (2mL PFS) or (2x1mL PFS) as above. 
2.8.1 
Adverse events (AEs) 
For adverse events and other binary safety variables crude incidence and exposure time-
adjusted incidence will be derived as described below and summarized in Table 2-7.  
All adverse events are summarized based on treatment emergent only. The definition for 
“treatment emergent” is as below: 
• events started after the first dose of study medication or events present prior to the first 
dose of study medication but increased in severity based on preferred term  
• and started prior to the last dose plus 84 days (inclusive)  
All adverse events will be listed with “treatment emergent” flag displayed. 
Table 2-7 
Overview of analyses on some safety endpoints 
Analysis period 
AEs & 
SPP/RMP 
risks 
(special AE 
interest) 
SAEs 
AEs-SMQ 
AEs by 
severity 
study treatment 
related AEs, 
death & other 
significant AEs 
notables 
(lab/vitals) 
treatment 
period 1 
(up to  
week 12) 
• crude 
incidence 
• crude 
incidence 
• crude 
incidence 
• crude 
incidence 
• crude 
incidence 
• crude 
incidence 
Entire treatment 
period 
(including all 
data) 
• crude 
incidence 
• exp.time 
adjusted 
incidence* 
• crude 
incidence 
• exp.time 
adjusted 
incidence* 
• crude 
incidence 
• exp.time 
adjusted 
incidence* 
• crude 
incidence 
• crude 
incidence 
• crude 
incidence 
*Note, 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 
• PT level for SAE 
• PT level for AE  ≥ 2% or incidence rate per 100 subject years ≥ 5.0 in any treatment 
group 
• Other selected AEs of special interest on lower levels (e.g. PT or SMQ level 2), if 
appropriate 


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The crude incidence of treatment emergent adverse events will be presented for the 
 
 treatment period including all data 
for final analysis. 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 using the score method including continuity correction (Newcombe 
1998) as described in Section 5.4.5. In addition, exposure time-adjusted incidence rates will be 
provided for the treatment period including all data (see Section 5.4.6). 
Adverse events will be summarized by presenting, for each treatment group, the number and 
percentage of subjects having at least one 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 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.  
Adverse events will also be summarized by standardized or customized MEdDRA queries 
(SMQ or CMQ/NMQ). The MedDRA version used for reporting the adverse events will be 
described in a footnote. 
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 grouping term table) will be presented in 
descending frequency according to its incidence in secukinumab group starting from the most 
common event. Here threshold value z is set to 2 (%) but it may be updated following review 
of the dry run outputs. 
A graphical display of the crude rates or exposure adjusted incidence rates within system organ 
classes will be presented as follows: For all AEs regardless of severity and seriousness, the 
point estimate within system organ classes will be presented graphically with system organ 
class on the y-axis. This figure will consist of two panels: i) point estimate of AEs, ii) point 
estimate of serious AEs. For the exposure adjusted incidences a linear-scale will be used on the 
x-axes. 
Separate summaries will be provided for deaths, serious adverse events, other significant 
adverse events leading to discontinuation and adverse events leading to dose adjustment or 
interruption. 
Algorithms for date imputations will be provided in Section 5. 
For SAEs occurred during screening a listing will be prepared for all subjects screened including 
screening failures. 
The adverse events occurred after the treatment errors in those subjects who received 
erroneously the wrong treatment at least once, will be listed. 
Other safety topics of interest, such as risks defined in the Safety Profiling Plan, Risk 
Management Plan or topics of interest regarding signal detection or routine analysis are defined 


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in the Program Case Retrieval Sheet 
 
 
Crude rate of important identified and potential risks from Case Retrieval Sheet will be provided 
for all (non-serious and serious) cases and for all serious cases. Exposure-time adjusted rates 
will be provided for treatment period including all data for all (non-serious and serious) cases 
and for all serious cases. In addition, listings will be provided for the related AE risks. 
Risk measures and confidence intervals will be derived according to Section 5. 
The version of the Case Retrieval Sheet used for the analyses will be described in a footnote. 
This includes MedDRA version and Novartis MedDRA Query (NMQ) dictionary date.  
Important note: For the evaluation of risks primary and secondary system organ classes of the 
MedDRA dictionary will be considered. 
For the legal requirements of ClinicalTrials.gov and EudraCT, two required tables on adverse 
events which are not serious adverse events with an incidence greater than 2% and on serious 
adverse events and SAE suspected to be related to study treatment will be provided by system 
organ class and preferred term on the safety set population. 
If for a same patient, several consecutive AEs (irrespective of study treatment causality, 
seriousness and severity) occurred with the same SOC and PT: 
• a single occurrence will be counted if there is  ≤ 1 day gap between the end date of the 
preceding AE and the start date of the consecutive AE 
• more than one occurrence will be counted if there is > 1 day gap between the end date 
of the preceding AE and the start date of the consecutive AE 
For occurrence, the presence of at least one SAE / SAE suspected to be related to study 
treatment / non SAE has to be checked in a block e.g., among AE’s in a ≤ 1 day gap block, if at 
least one SAE is occurring, then one occurrence is calculated for that SAE. 
The number of deaths resulting from SAEs suspected to be related to study treatment and SAEs 
irrespective of study treatment relationship will be provided by SOC and PT. 
2.8.2 
Deaths 
Separate summary and listing will be provided for deaths. 
2.8.3 
Laboratory data 
The summary of laboratory evaluations will be presented for two groups of laboratory tests 
(hematology and serum chemistry).  
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 
Only “on-treatment” laboratory data will be summarized (i.e. assessments within last dose plus 
84 days). All laboratory data will be listed with “on-treatment” flag displayed. If two 


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measurements are taken on the same date/time/CRF visit then use the average of two 
assessments. 
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 “>”).” For 
example, the actual lab result is “<5” and LLQ = 10, it will be reported for the numerical part 
as 5 and listed as “<5”, LLQ will be imputed as 5. 
In addition, shift tables may be provided as required at ad-hoc basis for all parameters to 
compare a subject’s baseline laboratory evaluation relative to the most extreme laboratory test 
value within a treatment period. For the shift tables, the normal laboratory ranges will be used 
to evaluate whether a particular laboratory test value is normal, low, or high (including category 
“high and low”). These summaries will be presented by laboratory test and treatment group. 
Subjects with abnormal laboratory values will be listed and values outside the normal ranges 
will be flagged. 
The following laboratory parameters will be analyzed with respect to numerical Common 
Terminology Criteria for Adverse Events (CTCAE) grades, given in Table 2-8: 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). 
The number and percentage of subjects with CTCAE grade newly occurring or worsening after 
baseline will be presented. These summaries will be split into hematology and chemistry. 
Table 2-8 
CTCAE grades for laboratory parameters to be analyzed 
CTCAE v4.0 Term 
Grade 1    
Grade 2    
Grade 3    
Grade 4    
HGB decreased 
(Anemia) 
<LLN – 100 g/L 
<100 – 80 g/L 
<80 g/L  
Life-threatening 
consequences; urgent 
intervention 
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 
>ULN - 1.5 x ULN 
>1.5 - 3.0 x ULN 
>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 
Shift tables will be presented comparing baseline laboratory result (CTCAE grade) with the 
worst results (expressed in CTCAE grade) during the treatment phase analyzed. Of note, 
baseline will be defined as last assessment prior to first dosing in initial treatment phase. If no 


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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, see Section 2.1.1.3. 
Exposure time adjusted incidence for subjects with newly occurring neutropenia of CTCAE 
grade >=2 will be summarized and listed in the listing. 
The number and percentage of subjects with newly occurring liver enzyme abnormalities will 
also be summarized based on the event criteria given in Table 2-9. 
Table 2-9 
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 
ALT or AST >3xULN & (nausea or vomiting or fatigue or general malaise or 
abdominal pain or (rash and eosinophilia)) 
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. 
ALT or AST>3xULN & TBL >2xULN & ALP <2xULN  (Potential Hy’s Law) or 
reported Hy’s Law case 
Note: “Hy’s Law case” is a lower level term in MedDRA (10070546) and may be 
reported as AE. 
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>5xULN. 
Individual subject data listings will be provided for subjects with newly occurring or worsening 
abnormal laboratory data. Data of subjects with newly occurring liver enzyme abnormalities 
will be listed in an additional listing. 
Fasting laboratory tests including fasting plasma glucose and fasting lipids will be evaluated 
only at screening. No analysis will be done for these measurements. 


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For urinalysis, standard dipstick measurements for specific gravity, protein, glucose, pH, blood, 
urine blood (non-hemolyzed), urine blood (hemolyzed), bilirubin, ketones, WBC will be done 
at screening. No analysis will be done for these measurements. 
2.8.4 
Other safety data 
2.8.4.1 
ECG and cardiac imaging data 
A standard 12-lead ECG will be performed at screening to assess the eligibility of subjects. No 
analysis will be done for ECG measurements. 
2.8.4.2 
Vital signs 
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. 
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 
Only “on-treatment” vital signs will be summarized (i.e. assessments within last dose plus 84 
days). All vital signs will be listed with “on-treatment” flag displayed. 
The number and percentage of subjects with newly occurring notable vital signs abnormalities 
will be presented. Criteria for notable vital sign abnormalities are provided in Table 2-10 below. 
A listing of subjects with newly occurring notably abnormal vital signs will be provided. 
Table 2-10 
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 
2.9 
Pharmacokinetics 
All completed subjects with quantifiable secukinumab serum concentration will be included in 
the pharmacokinetic data analysis.  
Serum concentrations will be expressed in mass per volume units. All concentrations below the 
limit of quantification as well as missing data will be labeled as such in the concentration data 
listings.  
Secukinumab serum concentrations will be summarized by visit and treatment group. In 
addition to mean, standard deviation (SD), coefficient of variation (CV), median and quartiles, 
the geometric mean and geometric coefficient of variation (CV) and n(log) will be presented. 
The formula for deriving the geometric mean and CV (%) is as following:  
• CV (%) = (SD/mean)*100, 
• geometric mean=exp( (sum of log transformed data) / number of non-missing data points 
after log transformation), 
• geometric CV = sqrt( exp( variance of log-transformed data)-1)*100. 


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Secukinumab serum concentration in the AIN457 300mg (2mL PFS) group will also be 
summarized by injections locations at previous 3 visits (i.e., though only, abdomen only, and 
though and abdomen) at Weeks 28 and 52. For Week 28, the previous injections locations at 
Weeks 16, 20 and 24 will be considered. Likewise for Week 52, the previous injections 
locations will be at Weeks 40, 44 and 48. 
In addition, concentration, sample date, sample time at pre-dose and minutes pre-dose, elapse 
time since day of first secukinumab dose, reason excluding from analysis will be listed by 
treatment sequence. Placebo subjects will also be listed.  
Values below lower limit of quantification/below detection limit will be imputed by 0. 
The analysis visit will refer to the visit as per the CRF.   
Pharmacokinetic parameters will be summarized by treatment group (AIN457 300mg 2mL PFS 
and AIN457 300 mg 2×1mL PFS). Descriptive summary statistics for Cmax and AUC84-112d 
include mean (arithmetic and geometric), SD, and CV (arithmetic and geometric), median, 
minimum and maximum. Tmax in days will be summarized as median, minimum and maximum. 
In addition, pharmacokinetic parameters will be listed by treatment sequence. 
The log-transformed parameters Cmax and AUC84-112d will be analyzed by a linear model, 
with treatment group (AIN457 300mg 2mL PFS and AIN457 300 mg 2×1mL PFS) as a fixed 
factor and body weight at baseline as covariate. For each of Cmax and AUC84-112d, the mean 
estimate and 90% confidence interval for the PK parameter ratio of “AIN457 300mg 2mL PFS” 
vs “AIN457 300 mg 2×1mL PFS” will be reported to represent the relative bioavailability for 
comparison.The log-transformed AUC84-112d at Week 12 in the AIN457 300mg (2mL PFS) 
group will be analyzed by a linear model, with injection location, laterality and body weight at 
baseline. The mean estimate and 90% confidence interval for the ratio of thigh vs abdomen and 
that of left vs right will be reported.  
In addition, a linear model with previous injections locations and body weight at baseline will 
be fitted for the log-transformed AUC84-112d at Week 12 in the AIN457 300mg (2mL PFS) 
group. The mean estimate and 90% confidence interval for the ratio of “thigh only” vs 
“abdomen only”, and that of “thigh and abdomen” vs “abdomen only” will be reported. For 
Week 12, the previous injections locations at randomization, Weeks 1, 2, 3, 4 and 8 will be 
considered. 
2.11 
Clinician-reported outcomes 
2.11.1 
Usability and hazard assessment of the 2 mL pre-filled syringe 
This analysis will be based on the Safety Set.  
The number and percentage of subjects who successfully completed each and ALL of the 
indicated steps as per the IFU will be summarized by visit and treatment group, including total. 


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The number and percentage of subjects who experienced each and ANY of the defined possible 
hazards will be summarized by visit and treatment group, including total. 
Successful self-injection will be positively defined for a subject when the subject performs the 
six critical steps as per the IFU (i.e. P8, P10, P11, P12, P13, P14). Number and percentage of 
subjects who passed the self-injection successfully as well as a two-sided 95% exact confidence 
interval at Week 1 visit will be summarized by visit and treatment group, including total. The 
following statistical hypothesis will be tested by an exact binomial test at one-sided 2.5% level 
of significance at Week 1 visit:  
H0: successful pre-filled syringe use rate < 90%  
H1: successful pre-filled syringe use rate ≥ 90%  
Missing values with respect to the self-assessment checklist and possible hazard assessment 
checklist will not be imputed while summarizing the answers of each question with frequencies.  
Subjects with one or more of the critical steps missing will be considered as unsuccessful 
(imputation with non-response) with regard to the self-injection success. Subjects who 
discontinued or who missed a visit and have the full self-injection checklist missing will not be 
evaluated with regard to the self-injection success at the corresponding visit.  
Visit windows will not be applied to self-injection assessment and possible hazard assessment. 
The analysis visit will refer to the visit as per the CRF. 
Of note: only data in the self-assessment checklist with self-injection checked in eCRF Dosage 
Administration Record (DAR) page are included in the analyses. 
2.12 
Patient-reported outcomes 
Summaries will be based on the FAS and will be presented separately for each treatment 
group. 
For DLQI 
 missing values will be replaced by LOCF. Baseline values will not be 
carried forward. If no pre-treatment value exists, values obtained after first dose of treatment 
can be used as baseline only if it was collected on the same day as first dose. In addition, missing 
baseline (PROs) values will be replaced by the means or modes of non-missing baseline values 
stratified by age group (<65 years, 65 years and older) and sex, for continuous scale or 
categorical/ordinal scale, respectively. 
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”. “Not relevant” is also a valid response. 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.  


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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. 
Treatment groups will be compared by Fisher’s exact test. 
Self-Injection Assessment Questionnaire (SIAQ) 
All SIAQ analyses will be based on the Safety Set. 
Summary statistics for the absolute values of the domain scores at Randomization (baseline) 
will be provided by treatment group including total for the PRE-module and the POST-module. 
The number and percentage of subjects in each of the 5 categories (likert scale) for each item 
will be presented by visit and treatment group including total. 
Item and domain scores from the PRE module taken before the first self-injection at 
Randomization (baseline) will be compared with the corresponding item and domain scores 
(feeling about injections, self-confidence domains, and overall satisfaction of self-injection item) 
from the POST modules. Change in domain scores from PRE module will be summarized by 
visit and treatment group including total. 
Domain scores will be calculated only if 50% or more items of the domain are completed. 
Missing items will not be imputed. Subjects who discontinued or who missed a visit and have 
the SIAQ questionnaire not completed will not be considered in the analyses at the 
corresponding visit. 
Of note: only SIAQ scores for those with self-injection checked in eCRF DAR page are 
included in the analyses. 


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3 
Sample size calculation 
A response rate of 8% for PASI 75 response and IGA mod 2011 0 or 1 response in the placebo 
group is expected, whereas a response rate of 62% for PASI 75 response and 55% for IGA mod 
2011 0 or 1 is the anticipated response in the secukinumab 300 mg 2 mL pre-filled syringe 
group. 
Placebo-response rates between 3% and 7% have been reported in Papp et al 2005, Menter et 
al 2008, Leonardi et al 2008, and Papp et al 2008. 


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3.1 
Primary endpoint (co-primary endpoint) 
With respect to the co-primary endpoint (PASI 75 response and IGA mod 2011 0 or 1 response 
at Week 12), the type-I-error will be 2.5% one-sided for comparison. With 70 subjects per group 
and assuming a response rate of 10% for PASI 75 response and IGA mod 2011 0 or 1 response 
in the placebo group, the power to show a response rate of 62% for PASI 75 response and 55% 
for IGA mod 2011 0 or 1 response in the secukinumab 300 mg 2 mL pre-filled group based on 
Fisher’s exact test (nQuery Advisor 6.01, two group Fisher’s-exact test of equal proportions) is 
above 99% for PASI 75 response and IGA mod 2011 0 or 1 response. 
3.1.1 
Secondary endpoints 
A power of 90% to show a response rate of 30% for PASI 100 in the secukinumab 300 mg 2 mL 
pre-filled group and 8% in the placebo group based on Fisher’s exact test results in a sample 
size of 70 subjects per group. Same power can be achieved if we apply the same assumption of 
PASI 100 response rate for secukinumab 300 mg 1 mL pre-filled group. 
A power of above 99% to show a response rate of 46% for PASI 90 in the secukinumab 300 mg 
2 mL pre-filled group and 8% in the placebo group based on Fisher’s exact test results in a 
sample size of 70 subjects per group. 
4 
Change to protocol specified analyses 
The primary and secondary efficacy endpoints will be analyzed using logistic regression model. 
Exact logistic regression will be performed in case of low response rates in the placebo group. 
The following analyses have been removed: 
• The maximum change (maximum decrease and maximum increase) from baseline 
within treatment period for each laboratory parameter  
• The stratified Van-Eltern testing and Hodges-Lehmann estimates for the absolute value 
and the percentage change from baseline of DLQI total score. 
5 
Appendix 
5.1 
Imputation rules 
5.1.1 
Study drug 
Any partial dates will be imputed as follows: 
We take the earlier day of  
• The last day in the month and  
• The calculated end day of the corresponding epoch 


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5.1.2 
AE date imputation 
Impute AE end date: 
1. If the AE end date ‘month’ is missing, the imputed end date should be set to the earliest of 
the (min (last visit date, last dose date + 84 days), 31DECYYYY, date of death).  
2. If the AE end date ‘day’ is missing, the imputed end date should be set to the earliest of the 
(min (last visit date, last dose date + 84 days), last day of the month, date of death).  
3. If AE ‘year’ is missing or AE is ongoing, the end date will not be imputed.  
 
Impute AE start date:  
Before imputing AE start date, find the AE start reference date.  
1. If the (imputed) AE end date is complete and the (imputed) AE end date < treatment start 
date then AE start reference date = min(informed consent date, earliest visit date).  
2. Else AE start reference date = treatment start date  
 
1. If the AE start date ‘year’ value is missing, the date uncertainty is too high to impute a 
rational date. Therefore, if the AE year value is missing, the imputed AE start date is set to 
NULL.  
2. If the AE start date ‘year’ value is less than the treatment start date year value, the AE 
started before treatment. Therefore:  
a. If AE ‘month’ is missing, the imputed AE start date is set to the mid-year point 
(01JulYYYY).  
b. Else if AE ‘month’ is not missing, the imputed AE start date is set to the mid-month 
point (15MONYYYY).  
3. If the AE start date year value is greater than the treatment start date year value, the AE 
started after treatment. Therefore:  
a. If the AE month is missing, the imputed AE start date is set to the year start point 
(01JanYYYY).  


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b. Else if the AE month is not missing, the imputed AE start date is set to the later of 
(month start point (01MONYYYY), AE start reference date + 1 day).  
4. If the AE start date year value is equal to the treatment start date year value:  
a. And the AE month is missing the imputed AE start date is set to the AE reference 
start date + 1 day.  
b. Else if the AE month is less than the treatment start month, the imputed AE start 
date is set to the mid-month point (15MONYYYY).  
c. Else if the AE month is equal to the treatment start date month or greater than the 
treatment start date month, the imputed AE start date is set to the later of (month start 
point (01MONYYYY), AE start reference date + 1 day).  
If complete (imputed) AE end date is available and the imputed AE start date is greater than 
the (imputed) AE end date, then imputed AE start date should be set to the (imputed) AE end 
date.  
5.1.3 
Concomitant medication date imputation 
Impute CM end date:  
1. If CM end day is missing and CM month/year are non-missing then impute CM day as the 
minimum of treatment end date and the last day of the month.  
2. If CM end day/month are missing and CM year is non-missing then impute CM day as the 
minimum of treatment end date and the end of the year (31DECYYYY).  
3. If imputed CM end date is less than the CM start date, use the CM start date as the imputed 
CM end date.  
Impute CM start date:  
1. If the CM start date year value is missing, the imputed CM start date is set to one day prior 
to treatment start date.  
2. If the CM start date year value is less than the treatment start date year value, the CM 
started before treatment. Therefore:  
a. If the CM month is missing, the imputed CM start date is set to the mid-year point 
(01JulYYYY).  
b. Else if the CM month is not missing, the imputed CM start date is set to the mid-
month point (15MONYYYY).  


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3. If the CM start date year value is greater than the treatment start date year value, the CM 
started after treatment. Therefore:  
a. If the CM month is missing, the imputed CM start date is set to the year start point 
(01JanYYYY).  
b. Else if the CM month is not missing, the imputed CM start date is set to the month 
start point (01MONYYYY).  
4. If the CM start date year value is equal to the treatment start date year value:  
a. And the CM month is missing or the CM month is equal to the treatment start date 
month, then the imputed CM start date is set to one day prior treatment start date.  
b. Else if the CM month is less than the treatment start date month, the imputed CM 
start date is set to the mid-month point (15MONYYYY).  
c. Else if the CM month is greater than the treatment start date month, the imputed CM 
start date is set to the month start point (01MONYYYY).  
If complete (imputed) CM end date is available and the imputed CM start date is greater than 
the (imputed) CM end date, then imputed CM start date should be set to the (imputed) CM 
end date.  
5.1.3.1 
Prior therapies date imputation 
See Section 5.1.3. 
5.1.3.2 
Post therapies date imputation 
See Section 5.1.3. 
5.1.4 
First diagnosis date (PsO, PsA) imputation 
1. If the first diagnosis day/ month are missing and the year is non-missing: 
a. If the year part of the first diagnosis date is equal to the year part of the inform 
consent date, then the imputed first diagnosis date is set to the year start point 
(01JanYYYY). 
b. Otherwise the imputed first diagnosis date is set to the mid-year point 
(01JulYYYY). 
2. If the first diagnosis day is missing and the month/year are non-missing: 


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a. If the month and year part of the first diagnosis date is equal to the month and year 
part of the inform consent date, then the imputed first diagnosis date is set to the 
month start point (01MONYYYY). 
b. Otherwise the imputed first diagnosis date is set to the mid-month point 
(15MONYYYY). 
5.1.5 
Other imputations 
Only PASI and IGA mod 2011 based response variables are imputed with multiple imputation 
or non-response, other response variables (e.g. DLQI 0 or 1 achievement) will be imputed with 
LOCF. 
For DLQI,
 missing values will be replaced by LOCF. Baseline values will not 
be carried forward. If no pre-treatment value exists, values obtained after first dose of treatment 
can be used as baseline only if it was collected on the same day as first dose. In addition, missing 
baseline (PROs) values will be replaced by the means or modes of non-missing baseline values 
stratified by age group (<65 years, 65 years and older) and sex, for continuous scale or 
categorical/ordinal scale, respectively. 
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 “>”).” 
5.2 
AEs coding/grading 
Adverse events will also be coded according to MedDRA dictionary, using a narrow search. 
The MedDRA version used for reporting the adverse events will be described in a footnote. 
Safety topics of interest, such as risks defined in the Safety Profiling Plan, Risk Management 
Plan or topics of interest regarding signal detection or routine analysis are defined in the 
Program Case Retrieval Sheet
 
 
5.3 
Laboratory parameters derivations 
See Section 2.8.3. 
5.4 
Statistical models 
5.4.1 
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 scores, summary statistics will be derived for absolute and 
percentage changes from baseline. 


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5.4.2 
Analysis of 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 pas 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 response variables (e.g. for IGA mod 2011 0 or 1, PASI 75, PASI 50, PASI 90 and PASI 
100 response) the placebo adjusted response rates (risk difference) including 95% confidence 
interval will be derived by visit. 
Figures will be provided for PASI 75 response (upper left) PASI 90 response (upper right), 
PASI 100 response (lower left) and IGA mod 2011 0 or 1 response (lower right) at Week 12 as 
dot plots displaying treatments on the x-axis and point estimates including 95% confidence 
intervals on the y-axis.  
For time courses of response variables, the point estimate at each time point including 95% 
confidence interval will be plotted. 
5.4.3 
Logistic regression 
Binary outcome variables, including PASI 50 / 75 / 90 / 100 response and IGA mod 2011 0 or 
1 response, will be evaluated using a logistic regression model with treatment regimen, baseline 
bodyweight and baseline PASI score. Odds ratios will be computed for comparisons of 
secukinumab dose regimen versus placebo utilizing the logistic regression model fitted.  
If response rates are 0% or 100% in one of the treatment groups odds ratio estimate and p-values 
will not be displayed in outputs, but “-” will be shown. 
The odds ratio will be calculated such that an odds ratio >1 is favorable for secukinumab. Using 
PROC GENMOD to calculate the confidence interval for the odds ratios assumes asymptotic 
normality of the Wald estimate for the regression coefficient. The 95% confidence interval for 
the regression parameter of the active treatment effect relative to control(s) will be calculated 
using an exponential transformation to create the confidence interval for the odds ratio. 
p
q
−
=1
(
),
0
for
0
,0
=
=
>
p
L
p
(
),
1
for
1
,1
=
=
<
p
U
p


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All p-values reported on linear hypotheses about regression coefficients will be based on the 
Wald tests from Type III analyses. In the SAS procedure PROC GENMOD, a Type III analysis 
will be performed by adding the model options: TYPE3, DIST=BIN, and LINK=LOGIT. 
Logistic regression will be applied to response variables at each visit. 
If logistic regression model does not converge, the following steps will be performed: 
1. Run the PROC GENMOD procedure with EXACT statement;  
2. If convergence not reached, remove the covariates from the model one by one until 
convergence is reached; start with continuous covariates (i.e., baseline bodyweight by 
replacing with body weight stratum, and then baseline PASI score), followed by removing 
categorical covariates (i.e., weight stratum);  
3. If convergence not reached, perform Fisher’s exact test. 
It should be noted that this model might not converge if response rates are too low. 
5.4.4 
Multiple imputations for response variables 
Primary and secondary endpoints will be evaluated by Logistic regression and odds ratio 
estimate as described in the primary analysis method with multiple imputations for missing 
values. In addition, logistic regression analysis for PASI 50, PASI 75, PASI 90, PASI 100 and 
IGA mod 2011 0 or 1 response by visits will be analyzed using multiple imputation method. 
In the multiple imputations analysis the response status will be imputed based on the individual 
treatment arm information. 
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.  
Summary statistics for PASI 50, PASI 75, PASI 90, PASI 100, and IGA mod 2011 0 or 1 
response by visit will be presented in contingency tables with multiple imputations method. 
The number of imputations will be set to 100, the seed for the random function will be set to 
4572323 for this study. To generate the multiple imputed data sets, the SAS procedure MI can 
be used as follows: 


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The input data set <pasi_iga> 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_iga> OUT=<impdata> SEED=457<studycode> NIMPUTE=100; 
 VAR <baseline weight> <failure to at least one biologic>  
     <number of previous systemic therapies>  
     <baseline PASI> <baseline IGA>  
     <change from baseline PASI week 1> - <change from baseline PASI week primary endpoint> 
     <IGA week1> - <IGA 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: 
 
DATA <impdata2>; 
 SET <impdata>; 
IF <change from baseline PASI week primary endpoint>/<baseline PASI>=0.75 THEN <PASI 75 response> =1; 
ELSE <PASI 75 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; 
 
The treatment differences for each imputed data set will then be evaluated by Logistic 
regression and ODDS ratio as described in Section 5.4.6.2. This analysis will be done by 


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_IMPUTATION_ for the comparison to the placebo treatment group. The model should be 
estimating response probability = 1 by using DESECENDING option. Using the ESTIMATE 
option in the GENMOD procedure and the ODS OUTPUT data set “Estimates” provides the 
estimate for the odds ratio and confidence intervals. 
 
PROC GENMOD <option>; 
CLASS <stratum> <treatment>; 
MODEL <response> = <explanatory variables> / link=logit dist=bin type3; 
BY <by-variables); 
ESTIMATE “OR. AIN 300 mg 2mL PFS VS. Placebo” <treatment> 1 0 -1/exp;  
ESTIMATE “OR. AIN 300 mg 2x1mL PFS VS. Placebo” <treatment> 0 1 -1/exp;  
ODS OUTPUT Estimates=Estimates; 
RUN; 
The MIANALYZE procedure expects the parameter estimate in the variables ESTIMATE, and 
the corresponding standard error in the variable STDERR. Measurements can be obtained from 
“Estimates” dataset by selecting the row with ODDS ratio estimates.  
 
Data <modified dataset>; 
  set Estimates; 
  if substr(label,1,3)= “Exp”; 
  ESTIMATE=LBetaEstimate; 
  STDERR=StdErr; 
  effect= “OR”; 
  if missing(ESTIMATE) or missing(STDERR) then delete; 
RUN;  
 
The estimates and standard errors based on the 100 imputed data are then combined by applying 
Rubin’s rules for multiple imputed data sets, see Little and Rubin (2002).  
Programming notes:  
• The variables ESTIMATE and STDERR in the input data set for the MIANALYZE 
procedure may not be missing. Records with missing values need to be deleted and the 
variable _IMPUTATION_ needs to be renumbered and regenerated since for each by-
group the procedure expects consecutive numbers starting at 1. 
• The ESTIMATE and STDERR in terms of odds ratios from logistic regressions will be 
transformed to follow a normal distribution before MIANALYZE procedure. They will 
be transformed back to Odds Ratio to get the corrected ESTIMATE and corresponding 
CIs.   
The SAS procedure MIANALYZE will be applied as follows: 
DATA <modified dataset_t>; 
 
SET <modified dataset>; 
 
estimate=log(ESTIMATE); 
 
stderr=(log(LBETAUPPERCL)-log(LBETALOWERCL))/(2*1.96); 
RUN ; 
 
ODS LISTING CLOSE; 
ODS OUTPUT ParameterEstimates=<results> VarianceInfo=<varinfo> ModelInfo=<modelinfo>; 
PROC MIANALYZE PARMS=<modified dataset>; 
  BY <by-variables>; 
  MODELEFFECTS ESTIMATE; 


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  SETDERR stderr; 
RUN; 
ODS LISTING; 
 
data <results_back>; 
 
set <results>; 
 
estimate=exp(ESTIMATE); 
 
LCLMEAN=estimate*exp(-1.96*stderr); 
 
UCLMEAN=estimate*exp(+1.96*stderr); 
RUN ; 
 
In case if logistic regression does not converge, risk difference estimates will be provided. The 
SAS procedure PROC FREQ for risk difference estimates will be applied as follows: 
 
ODS LISTING CLOSE; 
PROC FREQ DATA=<Imputed dataset> ORDER=DATA; 
     TABLES <treatment group>*<response variable>/riskdiff alpha=0.05; 
     BY <By-variables>; 
     ODS OUTPUT RiskDiffCol1=RiskDiffCol1; 
RUN; 
ODS LISTING; 
DATA DRISK; SET RiskDiffCol1; 
     WHERE control=“1”; 
     ESTIMATE=risk; 
     STDERR=ase; 
     effect=”Riskdiff”; 
     IF missing(ESTIMATE) OR missing(STDERR) THEN DELETE; 
RUN; 
PROC SORT DATA=DRISK; BY <By-variables>; RUN; 
ODS LISTING CLOSE; 
ODS OUTPUT ParameterEstimates=results VarianceInfo=varinfo ModelInfo=Modelinfo; 
PROC MIANALYZE PARAMS=drisk; 
     by <By-variables>; 
     modeleffects Riskdiff; 
     stderr ase; 
RUN; 
ODS LISTING; 
DATA results2; 
     set results; 
     or=estimate*100; 
     lowercl=(LCLmean)*100; 
     uppercl=(UCLmean)*100; 
     KEEP <response variable> <By-variables> or lowercl uppercl probt; 
RUN; 
 
5.4.5 
Crude incidence and related risk estimates 
5.4.5.1 
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. 


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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. 
However, the confidence interval derived via the score method including continuity correction 
will be the default in safety analyses. 
5.4.5.2 
Relative risk and 100*(1-α)% confidence interval 
For an investigational drug group with n1 subjects at risk, independent from the control group 
(e.g., placebo or comparator) with n0 subjects at risk, of whom x1 and x0 experience a certain 
event with probability π1 and π0 respectively, the relative risk is estimated as p1/p0 with p1=x1/n1 
and p0=x0/n0. 
An asymptotic 100*(1-α)% confidence interval on the relative risk will be based on the back-
transformed large sample confidence limits on the log-transformed relative risk estimate which 
are obtained by application of the delta-method and Slutzky’s theorem (Lachin 2000). The SAS 
procedure PROC FREQ with option RELRISK in the TABLES statement will be used to 
provide the asymptotic 100*(1-α)% confidence interval on the relative risk. The estimate is not 
computed if either x1 or x0 equals 0. In this case, or if the crude incidences are low in both 
groups, the relative risk will be approximated by the odds ratio for which an exact confidence 
interval will be obtained as specified in Section 5.4.6.3. If the relative risk is not well 
approximated by the odds ratio but asymptotic normality is questionable, STATXACT will be 
used. 
5.4.5.3 
Odds ratio and 100*(1-α)% confidence interval 
For an investigational drug group with n1 subjects at risk, independent from the control group 
(e.g. placebo) with n0 subjects at risk, of whom x1 and x0 experience a certain event with 
probability π1 and π0 respectively, the odds ratio is estimated as 
p
q
−
=1


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)
1
/(
)
1
/(
0
0
1
1
p
p
p
p
−
−
 with p1= x1/n1 and p0=x0/n0. A conditional exact 100*(1-α)% confidence interval 
will be obtained by using the SAS procedure PROC FREQ with statement EXACT OR. 
5.4.5.4 
Risk difference and 100*(1-α)% confidence interval 
For an investigational drug group with n1 subjects at risk, independent from the control group 
(e.g., placebo or comparator) with n0 subjects at risk, of whom x1 and x0 experience a certain 
event, the risk difference is estimated as p1-p0 with p1= x1/n1 and p0=x0/n0.  
Exact unconditional confidence limits for the risk difference will be obtained with SAS 
procedure PROC FREQ and option RISKDIFF in the TABLES statement, specifying the 
RISKDIFF option also in the EXACT statement.  
5.4.6 
Exposure adjusted incidence rate and related risk estimates 
5.4.6.1 
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. 
5.4.6.2 
Exposure-adjusted event rate and 100*(1-α)% confidence interval 
For each of n subjects tj (j=1,...,n) specifies the exposure time. The number of occurrences of a 
treatment emergent 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 events (episodes). 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 
T
c
L
D
2
,2
/
5.0
α
=
T
c
U
D 2
2
,
2
/
1
5.0
+
−
=
α


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(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 α th quantile of the Chi-square distribution with k degrees of freedom. 
5.5 
Rule of exclusion criteria of analysis sets  
Protocol deviations for exclusion from analysis sets are defined in Table 5-1.  
Table 5-1 
Subject classification rules 
Analysis set 
PD Categories Codes that 
cause subject to be excluded 
Non-PD criteria that cause a 
subject to be excluded 
Randomization set 
NA 
Misrandomized subject 
FAS (Full Analysis Set)  
DVSPID: INCL02; OTH30 
Misrandomized subject 
Safety 
DVSPID: INCL02; OTH30 
Subjects who did not take any 
study treatment 
INCL02: ICF missing or not signed prior to initiating study procedure 
OTH30: Severe ICH-GCP non-compliance of study site 
5.6 
Clinician reported outcomes 
5.6.1 
Usability and hazard assessment of the 2 mL pre-filled syringe 
The goal is to measure and evaluate the usability of the 2mL pre-filled syringe during observed 
use. During the first 2mL self-injection at the respective visits (Randomization and Week 1), 
site staff will observe and complete the self-injection assessment checklist (Table 5-2) to assess 
the ability to follow the instructions for use (IFU). The possible hazard checklist (Table 5-3) 
will be assessed for the 2mL self-injection at each of the two visits. 
Primary usability assessment: 
• Assessment of successful self-administration by the subject at Week 1. Successful self-
injection is achieved when the subject performs all required steps effectively and safely to 
deliver the correct dose from the device at the correct injection site. The sequence of user 
steps (as per IFU) that are minimally required are P8, P10, P11, P12, P13, P14 (Table 5-2), 
these 6 critical steps will be used to define successful administration. The general passing 
usability goal for ‘successful use’ task completion will be defined as ≥ 90% pass rate 
following these steps. 
Secondary usability assessment: 
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• Assessment of subject use errors that occur during the First Use at Randomization (after 
initial training) and repeated self-injection at Week 1 (without retraining). 
• Assessment of successful First Use by subject after initial training (at Randomization), for 
subjects who successfully perform the self-injection as defined above for the primary 
usability assessment (i.e. P8, P10, P11, P12, P13, P14). 
Table 5-2 
Self injection assessment checklist (pre-filled syringe) 
No. 
Instruction for use (IFU) indicated steps 
Required for 
successful 
administration 
P1 
Washed hands with soap and water 
No 
P2 
Cleaned the injection site 
No 
P3 
Removed the safety syringe from the outer box 
No 
P4 
Took syringe out of the tray 
No 
P5 
Checked expiration date on syringe label 
No 
P6 
Inspected the safety syringe for damage 
No 
P7 
Inspected liquid for brown discoloration or particles 
No 
P8 
Removed needle cap from safety syringe 
Yes 
P9 
Discarded needle cap 
No 
P10 
Pinched the skin at injection site 
Yes 
P11 
Inserted the needle into skin 
Yes 
P12 
Held onto the finger flange 
Yes 
P13 
Fully depressed plunger until end point 
Yes 
P14 
Held plunger pressed fully down and syringe in place for 5 
seconds 
Yes 
P15 
Kept plunger fully depressed while lifting the needle straight from 
injection site 
No 
P16 
Released the plunger 
No 
P17 
Allowed syringe guard to automatically activate and cover the 
needle 
No 
P18 
Disposed used safety syringe in a sharps container 
No 
Table 5-3 
Possible hazard assessment checklist 
No. 
Possible hazard assessment checklist 
H1 
Was there a needle stick in a critical area (e.g. eye, carotid artery)? 
H2 
Was there a needle stick in a non-critical area?1 
H3 
Was any part of the device swallowed? If yes, please specify. 
H4 
Was an immediate-type allergic reaction noticed to device material? 
H5 
Was increased pain noticed by the patient due to a bent needle? 
H6 
Was the breakage of the device observed?2 
H7 
Was swallowing of material debris observed?3 
H8 
Was any other problem observed?3  
H9 
Was less than the full dose administered?4 


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1 Excluding the actual injection into the appropriate injection site of the body 
2 If yes, then it is to be specified under which circumstances breakage occurred and which parts were 
affected, as well any additional problems (e.g. injuries) due to the breakage are to be described. 
3 If yes, then it is to be specified. Possible events might include: irritated skin; drug too cold when injected; 
the drug or device upon visual inspection appeared unsuitable for injection; intradermal instead of 
subcutaneous injection; and other events. 
4 If yes, then it is to be specified why, e.g. leakage from injection site, early removal. 
5.7 
Patient reported outcomes 
The impact of psoriasis on various aspects of subjects’ health-related quality of life will be 
assessed by the following instruments in this trial: 
• DLQI 
• 
 
5.7.1 
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 
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 


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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). 
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. 


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5.7.3 
Self-injection Assessment Questionnaire (SIAQ) 
The Self-Injection Assessment Questionnaire (SIAQ) is a questionnaire to measure overall 
subject experience with subcutaneous self-injection, and to investigate its psychometric 
properties. The SIAQ is composed of two modules: the PRE-module and the POST-module. 
The PRE-module, which is completed at Randomization before the first self-injection (baseline), 
includes 7 items grouped into three domains: feelings about injections, self-confidence and 
satisfaction with self-injection. The POST-module, which is completed following the two self-
injections, includes several items addressing five principal domains: feelings about injections, 
self-confidence, injection-site reactions, ease of use, satisfaction plus a single item assessing 
self-image. Subjects will rate each item of the SIAQ on a 5-point semantic Likert-type scale 
ranging from 1 (worst experience) to 5 (best experience). Item score will be transformed to 
obtain a score ranging from 0 (worst experience) to 10 (best experience). The domain score will 
then be calculated as the mean of the item scores included in the domain.  
Respondent rates each item of the PRE SIAQ and items 1-9 and 15-21 of the POST SIAQ on a 
5-point semantic Likert-type scale, and items 10-14 of the POST SIAQ on a 6-point semantic 
Likert-type scale. For all items, a score of 1 corresponds to the subject’s worst experience and 
a score of 5 or 6 corresponds to the subject’s best experience.  
The scoring of domains is performed in 2 steps: 
1. The raw item scores ranging from 1 to 5 are transformed into scores ranging from 0 (worst 
experience) to 10 (best experience). 
2. The transformed scores for items contributing to a domain are then averaged into a domain 
score (Table 5-5). 
Table 5-5 
Scoring of domains from raw item scores 
 
Items 
Transformed item score 
Domain score 
calculation 
Domain score 
range 
PRE-module domain 
FL 
1-3 
((raw score)-1)*2.5 
Average of 
transformed item 
scores 
0-10 
CO 
4-6 
((raw score)-1)*2.5 
SA 
7 
((raw score)-1)*2.5 
POST- module domain 


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FL=Feeling about injection, IM=Self-Image, CO=Self-Confidence, RE=Pain and skin reaction during or 
after the injection, EU=Ease of use of the self-injection device, SA=Satisfaction with Self-injection 
PRE-module: 
Item 1= In general, how afraid are you of needles?; 
Item 2= In general, how afraid are you of having an injection?; 
Item 3= How anxious do you feel about giving yourself an injection?; 
Item 4= How confident are you about giving yourself an injection in the right way?; 
Item 5= How confident are you about giving yourself an injection in a clean and sterile way?; 
Item 6= How confident are you about giving yourself an injection safely?; 
Item 7= Overall, how satisfied are you with your current way of taking your medication (self-injection)? 
POST-module: 
Item 1= In general, how afraid are you of needles?; 
Item 2= In general, how afraid are you of having an injection?; 
Item 3= How anxious do you feel about giving yourself an injection?; 
Item 4= How embarrassed would you feel if someone saw you with the self-injection device?; 
Item 5= How confident are you about giving yourself an injection in the right way?; 
Item 6= How confident are you about giving yourself an injection in a clean and sterile way?; 
Item 7= How confident are you about giving yourself an injection safely?; 
Item 8a= During and/or after the injection, how bothered were you by: pain”; 
Item 8b= During and/or after the injection, how bothered were you by: burning sensation”; 
Item 8c= During and/or after the injection, how bothered were you by: cold sensation”; 
Item 9a= During and/or after the injection, how bothered were you by: itching at the injection site?”; 
Item 9b= During and/or after the injection, how bothered were you by: redness at the injection site?”; 
Item 9c= During and/or after the injection, how bothered were you by: swelling at the injection site?”; 
Item 9d= During and/or after the injection, how bothered were you by: bruising at the injection site?”; 
Item 9e= During and/or after the injection, how bothered were you by: hardening at the injection site?”; 
Item 10= How difficult or easy was it to remove the cap?; 
Item 11= How difficult or easy was it to depress the device?; 
Item 12= How difficult or easy was it to administer the injection without any help?; 
Item 13= How difficult or easy was it to use the self-injection device?; 
Item 14= How does the device fit in your hand?; 
Item 15= How easy was it to give yourself an injection?; 
Item 16= How satisfied are you with how often you give yourself an injection?; 
Item 17= How satisfied are you with the time it takes to inject the medication?; 
Item 18= Overall, how satisfied are you with your current way of taking your medication 
(self-injection)?; 
Item 19= Overall, how convenient is the self-injection device?; 
Item 20= After this study, would you choose to continue self-injecting your medication?; 
Item 21= After this study, how confident would you be to give yourself injections at home? 
 
 
 
 
FL 
1-3 
((raw score)-1)*2.5 
Average of 
transformed item 
scores 
0-10 
IM 
4 
((raw score)-1)*2.5 
CO 
5-7 
((raw score)-1)*2.5 
RE 
8-9 
((raw score)-1)*2.5 
EU 
10-14 
((raw score)-1)*2 
SA 
15-21 
((raw score)-1)*2.5 


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6 
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