Conditions: Plaque Psoriasis
Keywords: Plaque psoriasis, auto-injector, 2 mL injection, secukinumab
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 122
Healthy volunteers: no

Brief summary:
The primary purpose of this study is to assess efficacy, safety and tolerability of a 2 mL pre-filled auto-injector (AI) of 300 mg secukinumab in patients with moderate to severe plaque psoriasis

Detailed description:
This is a 52-weeks multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in approximately 120 subjects with moderate to severe plaque-type psoriasis

Arms:
arm 1: Placebo to secukinumab s.c., provided in 2 mL auto-injector form arm 2: Placebo to secukinumab s.c., provided in 2 \* 1 ml prefilled syringe form arm 3: Secukinumab 300 mg provided in 2 mL auto-injector form arm 4: Secukinumab 300 mg provided as 2x 1 mL prefilled syringe of 150 mg/mL

Interventions: intervention 1: Placebo 2 mL auto-injector intervention 2: Placebo 1 mL prefilled syringe intervention 3: Secukinumab 2 mL auto-injector intervention 4: Secukinumab 1 mL prefilled syringe
Intervention descriptions: intervention 1: All Placebo patients until week 8 (included): 2 mL auto-injector Placebo + 2x 1 mL prefilled syringe Placebo s.c. at randomization, weeks 1, 2, 3, 4 and 8.

PASI 90 responders at week 12: 2 mL auto-injector placebo + 2x 1 mL prefilled syringe Placebo s.c. at weeks 12, 13, 14, 15, 16 and every 4 weeks thereafter until week 48.

PASI 90 non-responders at week 12: 2 mL secukinumab 300 mg auto-injector + 2x 1 mL prefilled syringe Placebo s.c. at weeks 12, 13, 14, 15, 16 and 4-weekly thereafter until week 48 intervention 2: All Placebo patients until week 8 (included): 2 mL auto-injector Placebo + 2x 1 mL prefilled syringe Placebo s.c. at randomization, weeks 1, 2, 3, 4 and 8.

PASI 90 responders at week 12: 2 mL auto-injector Placebo + 2x 1 mL prefilled syringe Placebo s.c. at weeks 12, 13, 14, 15, 16 and every 4 weeks thereafter until week 48.

PASI 90 non-responders at week 12: 2x 1 mL secukinumab 150 mg prefilled syringe + 2 mL auto-injector Placebo s.c. at weeks 12, 13, 14, 15, 16 and 4-weekly thereafter until week 48 intervention 3: 2 mL secukinumab 300 mg auto-injector + 2x 1 mL prefilled syringe Placebo s.c. at randomization, weeks 1, 2, 3, 4, 8, 12, 13, 14, 15 , 16 and 4-weekly thereafter until week 48 intervention 4: 2 x 1 mL secukinumab 150 mg prefilled syringe + 2 mL auto-injector Placebo s.c. at randomization, weeks 1, 2, 3, 4, 8, 12, 13, 14, 15, 16 and 4-weekly thereafter until week 48

Protocol document:
Prot_000.pdf: 
Novartis Research and Development 
Secukinumab (AIN457) 
   Clinical Trial Protocol CAIN457A2325 / NCT03589885
Multicenter, rAndomized, double-blind, placebo-conTrolled, 
52-week stUdy to demonstRatE the efficacy, safety and
tolerability of subcutaneous secukinumab injections with 2 
mL auto-injectors (300 mg) in adult subjects with moderate to 
severe plaque psoriasis – MATURE 
Document type: 
Clinical Trial Protocol 
EUDRACT number: 
2018-000518-39 
Version number: 
00 (Original Protocol) 
Clinical Trial Phase: 
IIIb 
Release date: 
09-Apr-2018
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 1.0 (01-Dec-2017) 


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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 5 
List of figures ...................................................................................................................... 6 
List of abbreviations ............................................................................................................ 7 
Glossary of terms ................................................................................................................. 9 
Protocol summary .............................................................................................................. 11 
1 
Introduction ....................................................................................................................... 16 
1.1 
Background ............................................................................................................ 16 
1.2 
Purpose .................................................................................................................. 17 
2 
Objectives and endpoints ................................................................................................... 18 
3 
Study design ...................................................................................................................... 19 
4 
Rationale ............................................................................................................................ 20 
4.1 
Rationale for study design ..................................................................................... 20 
4.2 
Rationale for dose/regimen and duration of treatment .......................................... 21 
4.3 
Rationale for choice of comparator ....................................................................... 21 
4.4 
Purpose and timing of interim analyses/design adaptations .................................. 22 
4.5 
Risks and benefits .................................................................................................. 22 
5 
Population .......................................................................................................................... 23 
5.1 
Inclusion criteria .................................................................................................... 24 
5.2 
Exclusion criteria ................................................................................................... 24 
6 
Treatment ........................................................................................................................... 26 
6.1 
Study treatment ...................................................................................................... 26 
6.1.1 
Investigational and control drugs .......................................................... 26 
6.1.2 
Additional study treatments .................................................................. 27 
6.1.3 
Treatment arms/group ........................................................................... 27 
6.1.4 
Treatment duration ................................................................................ 28 
6.2 
Other treatment(s) .................................................................................................. 28 
6.2.1 
Concomitant therapy ............................................................................. 28 
6.2.2 
Prohibited medication ........................................................................... 29 
6.2.3 
Rescue medication ................................................................................ 30 
6.3 
Subject numbering, treatment assignment, randomization .................................... 30 
6.3.1 
Subject numbering ................................................................................ 30 
6.3.2 
Treatment assignment, randomization .................................................. 31 
6.4 
Treatment blinding ................................................................................................. 31 
6.5 
Dose escalation and dose modification .................................................................. 32 
6.5.1 
Follow-up for toxicities ......................................................................... 32 


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6.6 
Additional treatment guidance ............................................................................... 32 
6.6.1 
Treatment compliance ........................................................................... 32 
6.6.2 
Emergency breaking of assigned treatment code .................................. 32 
6.7 
Preparation and dispensation ................................................................................. 33 
6.7.1 
Handling of study treatment and additional treatment .......................... 33 
6.7.2 
Instruction for prescribing and taking study treatment .......................... 34 
7 
Informed consent procedures............................................................................................. 35 
8 
Visit schedule and assessments ......................................................................................... 36 
8.1 
Screening ............................................................................................................... 41 
8.1.1 
Information to be collected on screening failures ................................. 41 
8.2 
Subject demographics/other baseline characteristics ............................................. 41 
8.2.1 
Demographics ....................................................................................... 41 
8.2.2 
Psoriasis medical history/previous psoriasis therapies .......................... 41 
8.2.3 
Smoking history .................................................................................... 42 
8.2.4 
Cardiovascular medical history ............................................................. 42 
8.2.5 
Medical history ...................................................................................... 42 
8.2.6 
Determination of the tuberculosis status ............................................... 42 
8.3 
Efficacy .................................................................................................................. 42 
8.3.1 
Investigator’s Global Assessment (IGA mod 2011) .............................. 42 
8.3.2 
Assessment of total Body Surface Area (BSA) and Psoriasis Area 
Severity Index (PASI) ........................................................................... 43 
8.3.3 
Appropriateness of efficacy assessments .............................................. 45 
8.4 
Safety/Tolerability ................................................................................................. 45 
8.4.1 
Laboratory evaluations .......................................................................... 47 
8.4.2 
Electrocardiogram (ECG) ..................................................................... 48 
8.4.3 
Pregnancy .............................................................................................. 49 
8.4.4 
Appropriateness of safety measurements .............................................. 49 
8.5 
Additional assessments .......................................................................................... 49 
8.5.1 
Clinical Outcome Assessments (COAs) ................................................ 49 
 
 54 
8.5.3 
Biomarkers ............................................................................................ 55 
8.5.4 
Other assessments ................................................................................. 55 
9 
Study discontinuation and completion .............................................................................. 55 
9.1 
Discontinuation ...................................................................................................... 55 
9.1.1 
Discontinuation of study treatment ....................................................... 55 
9.1.2 
Withdrawal of informed consent ........................................................... 57 
9.1.3 
Lost to follow-up ................................................................................... 57 


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9.1.4 
Early study termination by the sponsor ................................................. 57 
9.2 
Study completion and post-study treatment ........................................................... 58 
10 Safety monitoring and reporting ........................................................................................ 58 
10.1 
Definition of adverse events and reporting requirements ...................................... 58 
10.1.1 
Adverse events ...................................................................................... 58 
10.1.2 
Serious adverse events........................................................................... 60 
10.1.3 
SAE reporting ........................................................................................ 61 
10.1.4 
Pregnancy reporting .............................................................................. 62 
10.1.5 
Reporting of study treatment errors including misuse/abuse ................ 62 
10.2 
Additional Safety Monitoring ................................................................................ 63 
11 Data Collection and Database management ...................................................................... 63 
11.1 
Data collection ....................................................................................................... 63 
11.2 
Database management and quality control ............................................................ 63 
11.3 
Site monitoring ...................................................................................................... 64 
12 Data analysis and statistical methods ................................................................................ 64 
12.1 
Analysis sets .......................................................................................................... 65 
12.2 
Subject demographics and other baseline characteristics ...................................... 65 
12.3 
Treatments ............................................................................................................. 66 
12.3.1 
Study treatment ..................................................................................... 66 
12.3.2 
Prior and concomitant medication......................................................... 66 
12.4 
Analysis of the primary variables .......................................................................... 66 
12.4.1 
Definition of primary endpoint(s) ......................................................... 66 
12.4.2 
Statistical model, hypothesis, and method of analysis .......................... 67 
12.4.3 
Handling of missing values/censoring/discontinuations ....................... 68 
12.4.4 
Sensitivity analyses ............................................................................... 68 
12.5 
Analysis of secondary endpoints ........................................................................... 68 
12.6 
Analysis of other secondary and exploratory endpoints ........................................ 69 
12.6.1 
Efficacy Endpoints ................................................................................ 69 
12.6.2 
Safety Endpoints ................................................................................... 69 
12.6.3 
Health-related Quality of Life - Dermatology Life Quality Index 
(DLQI) ................................................................................................... 70 
12.6.4 
Self-Injection Assessment Questionnaire (SIAQ) ................................. 71 
12.6.5 
Resource utilization ............................................................................... 71 
 
 71 
12.6.7 
DNA ...................................................................................................... 71 
12.6.8 
Biomarkers ............................................................................................ 72 
 
 72 


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12.7 
Interim analyses ..................................................................................................... 72 
12.8 
Sample size calculation .......................................................................................... 72 
12.8.1 
Primary endpoint(s) ............................................................................... 72 
12.8.2 
Secondary endpoint(s) ........................................................................... 72 
13 Ethical considerations and administrative procedures ...................................................... 72 
13.1 
Regulatory and ethical compliance ........................................................................ 72 
13.2 
Responsibilities of the investigator and IRB/IEC .................................................. 73 
13.3 
Publication of study protocol and results ............................................................... 73 
13.4 
Quality Control and Quality Assurance ................................................................. 73 
14 Protocol adherence ............................................................................................................ 73 
14.1 
Protocol amendments ............................................................................................. 74 
15 References ......................................................................................................................... 75 
16 Appendices ........................................................................................................................ 78 
16.1 
Appendix 1: Clinically notable laboratory values and vital signs ......................... 78 
 
 ..... 79 
16.3 
Appendix 3: Scoring of the SIAQ .......................................................................... 79 
16.4 
Appendix 4: SIAQ Questionnaire .......................................................................... 81 
16.5 
Appendix 5: DLQI Questionnaire .......................................................................... 88 
16.6 
Appendix 6: Determination of Tuberculosis status ............................................... 89 
 
 
List of tables 
Table 2-1 
Objectives and related endpoints........................................................... 18 
Table 6-1 
Prohibited medication ........................................................................... 29 
Table 8-1 
Assessment schedule ............................................................................. 38 
Table 8-2 
The IGA mod 2011 rating scale ............................................................ 43 
Table 8-3 
The PASI scoring system ...................................................................... 44 
Table 8-4 
Physical Assessments ............................................................................ 46 
Table 8-5 
Self-injection assessment check list (auto-injector) .............................. 50 
Table 8-6 
Possible hazard assessment check list (auto-injector) ........................... 51 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse ......................................................................................... 62 
 
 79 
 
 79 
Table 16-3 
Scoring of SIAQ domains from raw item scores ................................... 80 


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List of figures 
Figure 3-1 
Study design .......................................................................................... 20 
Figure 16-1 
Tuberculosis screening flowchart .......................................................... 91 


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List of abbreviations 
AE 
Adverse Event 
AI 
Auto-Injector 
ALT/AST 
Alanine Aminotransferase/Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Classification 
BDR 
Bioanalytical Data Report 
BSA 
Body Surface Area 
CD 
Cluster of Differentiation 
CFR 
Code of Federal Regulations 
CHMP 
Committee for Medicinal Products for Human use 
ClinRO 
Clinical Reported Outcomes 
CMO & PS 
Chief Medical Office and Patient Safety 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DLQI 
Dermatology Life Quality Index 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EMA 
EOS 
European Medicines Agency 
End Of Study 
EOT1/EOT2 
End of Treatment 1/End of Treatment 2 
EU 
European Union 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
hCG 
Human Chorionic Gonadotropin 
HRQoL 
Health Related Quality of Life 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IFU 
Instructions For Use 
IGA mod 2011 
Investigator’s Global Assessment modified 2011 
IL 
Interleukin 
IN 
Investigator Notification 
i.v.
Intravenous(ly) 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
IRT 
Interactive Response Technology 
LLN 
Local Lab Normal 
MedDRA 
Medical Dictionary for Regulatory Activities 
NIH 
National Institutes of Health 
PASI 
Psoriasis Area and Severity Index 
PFS 
Pre-Filled Syringe 
 
 
PRO 
Patient Reported Outcome 


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PsA 
Psoriatic Arthritis 
SAE 
Serious Adverse Event 
s.c. 
Subcutaneous(ly) 
SIAQ 
Self-Injection Assessment Questionnaire 
SGOT 
Serum Glutamic Oxaloacetic Transaminase 
SGPT 
Serum Glutamopyruvate Transferase 
SST 
Serum Separator Tubes 
SUSARs 
Suspected Unexpected Serious Adverse Reactions 
TB 
Tuberculosis 
TNFα 
Tumor Necrosis Factor alpha 
UK 
United Kingdom 
USA 
United Sates of America 
ULN 
Upper Limit of Normal 
UV 
Ultraviolet 
WBC 
White Blood Cell 
WHO 
World Health Organization 
 


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Glossary of terms 
Control drug 
Drug(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 subject in a 
time unit (eg, 100 mg once a day, 75 mg twice a day) 
Enrollment 
Point/time of subject entry into the study at which 
informed consent must be obtained (eg, prior to 
starting any of the procedures described in the 
protocol) 
Period 
A portion of the study which serves a specific purpose. 
Typical periods 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 (Code 
of Federal Regulations) 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 subjects/subjects 
with established disease and in those with newly- 
diagnosed disease. 
Subject number 
A unique number assigned to each subject upon 
signing the informed consent. This number is the 
definitive, unique identifier for the subject and should 
be used to identify the subject throughout the study for 
all data collected, sample labels, etc. 
Randomization number 
A unique identifier assigned to each randomized 
subject, corresponding to a specific treatment arm 
assignment 
Study drug/treatment 
Any single drug or combination of drugs administered 
to the subject as part of the required study procedures; 
includes investigational drug (s), placebo/comparator 
active drug run-ins or background therapy 
Study Treatment Discontinuation 
When the subject 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 study consent 
Withdrawal of consent from the study occurs only when 
a subject does not want to participate in the study any 
longer, and does not allow any further collection of 
personal data 


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Personal Data 
Subject information collected by the Investigator that is 
transferred to Novartis for the purpose of the clinical 
trial. This data includes subject identifier information, 
study information and biological samples 


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Protocol summary 
Protocol number 
CAIN457A2325 
Full Title 
Multicenter, rAndomized, double-blind, placebo-conTrolled, 
52-week stUdy to demonstRatE the efficacy, safety and 
tolerability of subcutaneous secukinumab injections with 2 mL 
auto-injectors (300 mg) in adult subjects with moderate to 
severe plaque psoriasis - MATURE 
Brief title 
Study of efficacy and safety of secukinumab 2 mL auto-injector 
(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 a 2 mL pre-filled auto-injector (AI) of 300 mg 
secukinumab. Results of this study will support the registration 
of secukinumab 300 mg 2 mL auto-injector. 
This 52-week, double-blind, randomized, parallel-group, and 
placebo-controlled study is using the recommended dose of 
300 mg secukinumab which has been approved in Japan, 
United States of America (USA) , European Union (EU), 
Switzerland and other countries for the treatment of moderate 
to severe psoriasis in adults 
Primary Objective(s) 
The primary objective is to demonstrate the efficacy of 
secukinumab 300 mg when administered in 2 mL auto-injector 
in subjects with plaque-type psoriasis with respect to both 
Psoriasis Area and Severity Index (PASI) 75 and Investigator’s 
Global Assessment modified 2011 (IGA mod 2011) 0 or 1 
response (co-primary endpoint) at Week 12, compared to 
placebo 
Secondary Objectives 
Key secondary objective 
To demonstrate the efficacy of secukinumab 300 mg when 
administered with a 2 mL auto-injector in subjects with plaque- 
type psoriasis with respect to PASI 90 at Week 12, compared 
to placebo. 
Other secondary objectives 
• To assess the efficacy of secukinumab 300 mg when 
administered with a 2 mL auto-injector in subjects with 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 auto-injectors as assessed by vital 
signs, clinical laboratory variables, and adverse events (AE) 
monitoring, compared to placebo. 
• To assess the subject usability (ability to follow instructions 
for use (IFU) and potential use-related hazards) and 
satisfaction with the new secukinumab 2 mL auto-injectors 
utilizing a self-administered Self-Injection Assessment 
Questionnaire (SIAQ) and investigator/site staff observation of 
secukinumab 300 mg 2 mL auto-injector administration. 


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• To investigate the effects of secukinumab 300 mg when 
administered with a 2 mL auto-injectors 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-week multicenter, randomized, double-blind, 
placebo-controlled, parallel-group trial in approximately 120 
subjects with moderate to severe plaque-type psoriasis. 
The study consists of 3 periods: Screening Period (of at least 1 
week and up to 4 weeks), Treatment Period 1 (12 weeks) and 
Treatment Period 2 (40 weeks). 
Subjects will be randomized using a 2:2:1:1 ratio to the following 
groups following a stratification by body weight (< 90 .kg or ≥ 90 
kg): secukinumab 300 mg regimen group (2 mL auto-injector), 
secukinumab 300 mg regimen group (2 x 1 mL pre-filled 
syringes (PFS)). Placebo – Secukinumab 300 mg (2 mL AI) or 
to Placebo – Secukinumab 300 mg (2 x 1mL PFS). The 
treatment of the 2 placebo groups will be the same during 
treatment Period 1 and will only differ after Week 12 in treatment 
period 2 for non-responders only. 
Prior to administration of the Week 12 dose, PASI 90 response 
will be evaluated and subjects classified accordingly. Based on 
the PASI 90 responders at the Week 12 visit, subjects on 
placebo will either remain on placebo during the Treatment 
Period 2 or be re-assigned to secukinumab 300 mg treatment 
(2 mL AI or 2 x 1mL PFS). 
Population 
Approximately 120 subjects with moderate to severe plaque 
psoriasis will be randomized in approximately 30 centers 
worldwide. Approximately 150 subjects are expected to be 
screened to provide the number of randomized subjects. 
Key Inclusion 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 


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• Phototherapy and/or 
• Previous systemic therapy 
Key Exclusion criteria 
1. Forms of psoriasis other than chronic plaque-type (eg, 
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. Subjects not 
willing to limit Ultraviolet (UV) light exposure (eg, 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 Interleukin (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. 
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 human 
chorionic gonadotropin (hCG) laboratory test. 
7. 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). 
8. 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 as one 2 mL auto-injector 
Control Treatment: 
• Secukinumab 300 mg, provided as two 1 mL pre-filled 
syringes (containing 150 mg secukinumab each) 
• Secukinumab placebo, provided as one 2 mL auto-injector 
and two 1 mL pre-filled syringes containing placebo matching 
secukinumab 
Efficacy assessments 
• IGA mod 2011 
• PASI 


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Key safety assessments 
• Evaluation of all AEs and Serious AEs (SAEs) 
• Physical examination 
• Vital signs 
• Height and weight 
• Laboratory evaluations (including hematology, clinical 
chemistry, fasting laboratory evaluations, urinalysis) 
 
 
 
• ECG 
• Pregnancy 
 
• Usability and hazard assessment of the auto-injector 
• Self-Injection Assessment Questionnaire (SIAQ) 
• Dermatology Life Quality Index (DLQI) 
• 
 
Data analysis 
Treatment groups for analyses will include: 
Primary week 12 analysis: 
• secukinumab 300 mg 2 mL Auto-injector (AI), secukinumab 
150 mg 1 mL Pre-Filled Syringe (PFS) x 2, and placebo 
• Entire study: secukinumab 300 mg 2 mL AI, secukinumab 
150 mg 1 mL PFS x 2, placebo switched secukinumab 300 mg 
2 mL AI, placebo switched secukinumab 150 mg 1 mL PFS x 
2, any secukinumab 300 mg 2 mL AI, any secukinumab 150 
mg 1 mL PFS x 2, any secukinumab 300 mg and placebo 
The following hypotheses will be included in co-primary testing 
procedure: 
• H1: secukinumab 300 mg (2 mL AI) is not superior to 
placebo with respect to PASI 75 response at Week 12 
• H2: secukinumab 300 mg (2 mL AI) is not superior to 
placebo with respect to IGA mod 2011 0 or 1 response at 
Week 12 
Within each of hypotheses H1 and H2 is tested at α = 2.5% 
(one-sided). The testing sequence will continue to key 
secondary endpoint PASI 90 at α = 2.5% (one-sided) only if 
both H1 and H2 have been rejected at α (one-sided) such that 
a family-wise type-I-error of α (one-sided) is kept. 
• H3: secukinumab 300 mg (2mL AI) is not superior to 
placebo with respect to PASI 90 response at Week 12 
The primary analysis method will be the logistic regression with 
treatment group; baseline bodyweight strata and baseline PASI 
score as explanatory variables. Odds ratios will be computed 
for comparisons of secukinumab dose regimen versus placebo 
utilizing the logistic regression model fitted. In case the logistic 
regression does not converge, an exact logistic regression will 
be performed. 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. 


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Missing data will be imputed using multiple imputations (MI) 
method as primary imputation method. 
Key words 
psoriasis, PASI, IGA mod 2011, secukinumab, auto-injector 


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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 and 
Mrowietz 2003, Griffiths and Barker JNWN 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 
healthcare 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 (eg, 
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 (eg, not 
achieving a decrease in 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-Interleukin (IL) 12/23 class of biological drugs provided clinicians with 
another treatment option (Kerdel and Zaiac 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 have been investigated in Phase III 
studies for the treatment of a range of immune mediated inflammatory diseases (Puig 2014) 
amongst which ixekizumab and brodalumab have been approved in 2017 in USA for moderate 
to severe psoriasis patients. 
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 


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and neutralizes the bioactivity of this cytokine. IL-17A is the central cytokine of a newly defined 
subset of inflammatory T cells, the T helper 17 cells which, in several animal models, are pivotal 
in multiple autoimmune and inflammatory processes. IL-17A is produced by memory effector 
CD4+ and CD8+ T lymphocytes, but also largely by innate immune cells (including neutrophils, 
mast cells, γδ-T cells, ILC3 cells, NK and iNKT cells), 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., IL-17A). Secukinumab (Cosentyx®) with a recommended 
dose of 300 mg was approved in 2014 in Japan, and 2015 in USA, EU, Switzerland, and in 
many 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 (AI). 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 pre-filled syringe and the 2 mL auto-injector 
containing 300 mg of secukinumab. 
As of 25 June 2017, over 28 000 subjects have been enrolled in studies with secukinumab, with 
over 25000 having 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 2017, there are over 50 completed and multiple ongoing trials conducted 
with secukinumab in indications including psoriasis, psoriatic arthritis (PsA), 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 Novartis 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, 
 and local 
tolerability of a 2 mL auto-injector of 300 mg secukinumab. 
 
1.2 
Purpose 
The purpose of this study is to demonstrate efficacy of secukinumab 300 mg in 2 mL auto- 
injector at Week 12 based on PASI and IGA mod 2011 response rates versus placebo in subjects 
with moderate to severe plaque-type psoriasis. 
Moreover this study will assess the efficacy, safety and tolerability of secukinumab when used 
for 52 weeks as well as usability (ability to follow instruction for use and potential use-related 
hazards) of the 2 mL AI. 
As a result, this study will provide efficacy, 
 and safety data (
) 
to support the registration of the secukinumab 300 mg in 2 mL AI. 


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2 
Objectives and endpoints 
Table 2-1 
Objectives and related endpoints 
Objective(s) 
Endpoint(s) 
Primary Objective(s) 
• To demonstrate the efficacy of secukinumab 300 
mg when administered in 2 mL auto-injector 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. 
Key Secondary Objective 
• 
To demonstrate the efficacy of secukinumab 300 mg 
when administered in 2 mL AI in subjects with 
plaque-type psoriasis with respect to PASI 90 at 
Week 12, compared to placebo. 
Other Secondary Objective(s) 
 
• 
To assess the efficacy of secukinumab 300 mg 
when administered in 2 mL AI in subjects with 
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 AI as assessed by vital 
signs, clinical laboratory variables, and adverse 
events monitoring, compared to placebo. 
 
 
• 
To assess the subject usability (ability to follow 
instructions for use and potential use-related 
hazards) and satisfaction with the new secukinumab 
2 mL AI utilizing a self-administered SIAQ and 
investigator/site staff observation of secukinumab 
300 mg 2 mL AI administration. 
 
 
• 
To investigate the effects of secukinumab 300 mg 
when administered in 2 mL AI with respect to DLQI 
0 or 1 achievement and DLQI changes at Week 12 
compared to placebo, and over time up to Week 52. 
Endpoint(s) for primary objective(s) 
• 
PASI 75 response at Week 12 and 
IGA mod 2011 0 or 1 response at 
Week 12 
 
 
 
Endpoint for key secondary objective 
• 
PASI 90 response at Week 12 
 
 
 
Endpoint(s) 
for 
other 
secondary 
objective(s) 
• 
PASI score and IGA mod 2011 score 
at each visit up to week 52 
• 
PASI 50, PASI 75, PASI 90, PASI 100 
and IGA mod 2011 0 or 1 response at 
each visit up to week 52 
 
 
• 
Treatment emergent adverse events, 
change from baseline to each study 
visit in clinical laboratory variables and 
vital signs 
 
 
• 
Successful self-injection, subject use 
errors, item and domain scores from 
the SIAQ, change in SIAQ domain 
scores 
 
 
 
 
• 
DLQI 0 or 1 score at each visit 
• 
Change from baseline in each of the 
seven DLQI scores and in the DLQI 
total score 
 
 


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Objective(s) 
Endpoint(s) 
 
 
 
 
 
 
 
 
 
3 
Study design 
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in 
approximately 120 subjects with moderate to severe plaque-type psoriasis. 
It is expected that subjects will be enrolled at around 30 study sites worldwide. 
The study consists of 3 periods: 
• Screening Period (of at least 1 week and up to 4 weeks between Screening and 
Randomization) 
The screening period is used to assess eligibility of the subjects and to taper subjects off 
prohibited medications. 
• Treatment Period 1 (of 12 weeks, double-blind between Randomization and Week 12 pre- 
dose) 
The Treatment Period 1 starts with the randomization of eligible subjects followed by the first 
dosing. At the start of Treatment Period I, eligible subjects will be randomized at a 2:2:1:1 ratio 
to one of the four treatment groups (Section 6.1.1). In order to achieve a balanced weight 
distribution in each treatment arm, randomization in these four groups will be stratified by body 
weight at baseline (< 90 kg or ≥ 90 kg). Subjects are then visiting the study site at Week 1, 2, 
3, 4, 8 and 12, where they will receive study treatment (secukinumab 300 mg 2 mL AI, 
secukinumab 300 mg 2 x 1mL PFS, or placebo). 


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Assessments for the primary endpoints are done for all treatment arms at Week 12 prior to 
dosing. This time-point is the End of Treatment Period 1 (EOT1). 
• Treatment Period 2 (of 40 weeks, double-blind between Week 12 dosing and Week 52) 
The Treatment Period 2 is a maintenance period for the study treatment and starts with the Week 
12 dosing. Doses of study treatment are then self-administered weekly up to Week 16 and every 
four weeks up to Week 48 for all treatment arms. 
Week 52 is the planned End of Treatment Period 2/End of Study (EOT2/EOS). 
Subjects who prematurely discontinue study treatment must perform EOT1 or EOT2/EOS 
approximately four weeks after their last dose of study treatment, depending if they are in 
Treatment Period 1 or 2, respectively. 
Safety, efficacy 
 will be performed 
according to the visit schedule as described in Table 8-1. 
 
Figure 3-1 
Study design 
 
In the figure, the solid arrow means active drug dosing while the dotted arrow means placebo dosing. 
 
4 
Rationale 
4.1 
Rationale for study design 
The intent of this study is to assess a 2 mL auto-injector form for the administration of 300 mg 
of secukinumab instead of two injections of 1 mL pre-filled syringes of 150 mg each, to 
psoriasis subjects that are treated with secukinumab at the recommended dose. 


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This 52-week, double-blind, randomized, parallel-group, and placebo-controlled study is using 
the recommended dose of 300 mg secukinumab which has been approved for the treatment of 
moderate to severe psoriasis in adults. 
The study has been designed in accordance with Health Authorities guidelines and feedback on 
the clinical development program for the 2 mL auto-injector, including the United States Food 
and Drug Administration (FDA). 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 2016). 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 CAIN457A2325. 
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 (1 mL pre-filled syringe in 
CAIN457A2308, and 1 mL auto-injector in CAIN457A2309; Blauvelt et al 2014, Paul C et al 
2015). 
Overall, this study will assess the efficacy, 
 safety (
) and 
tolerability of secukinumab when used both, short-term (up to 12 weeks) and long-term (up to 
52 weeks) and includes an usability and satisfaction assessment (ability to follow instruction 
for use and potential use-related hazards) and satisfaction) of secukinumab with a 2 mL auto- 
injector. These data will support the registration of secukinumab 300 mg 2 mL auto-injector. 
The subject population will be described in more detail in Section 5 below. 
 
4.2 
Rationale for dose/regimen and duration of treatment 
The placebo-controlled study design was chosen to demonstrate the efficacy of 300 mg 
secukinumab administered with a 2 mL auto-injector in adult subjects suffering from moderate 
to severe psoriasis compared to placebo. The selected dose regimen for this study with an initial 
weekly schedule up to 4 weeks followed by a 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 
 and safety profile with the secukinumab 300 
mg 2 mL auto-injector. 
 
4.3 
Rationale for choice of comparator 
Due to the nature of psoriasis and the outcome measures for the primary and the key secondary 
endpoints used (PASI 75, 90 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 


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the indication of plaque-type psoriasis. Subjects from the placebo group that will not achieve 
PASI 90 after Week 12 will receive secukinumab. 
An arm with secukinumab 300 mg as 2 injections of 1 mL PFS has been added to assess 
 
 and as a reference for comparisons of efficacy and safety with secukinumab 300 
mg 2 mL AI. 
 
4.4 
Purpose and timing of interim analyses/design adaptations 
An analysis is planned to be performed after all subjects have completed the Week 16 visit to 
assess the 
 data up to Week 16 with the coprimary endpoints. 
All data up to Week 16 will be collected with the clinical team being blinded. The designated 
Novartis personnel (eg, statistician, programmer and a clinical representative) will be unblinded 
following database lock for the Week 16 analysis after all subjects have completed Week 16. 
Investigators, site personnel, and subjects will remain blinded until the end of the study. 
It is planned that data from the Week 16 analysis will be used for submission to the Health 
Authorities. Trial modifications are not planned based on any Week 16 analysis. 
Additional analyses are not planned, they may be performed to support Health Authorities 
interactions, as necessary. 
 
4.5 
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. 
Approximately 4,000 patients with moderate to severe plaque psoriasis were included in studies 
in the registration program. This included 3,430 subjects 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 
 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 
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. 


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Indirect comparisons across phase III trials revealed that 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 subjects with a simple easy to use 
single-injection device for the treatment of psoriasis. 
The principle of a 2 mL s.c. injection in patients is supported by the Patient Education document 
from the US National Institute of Health (NIH) that outlines the possibility to administer more 
than 1 mL of volume (NIH 2016). 
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 auto-injector, and therefore it 
is appropriate to initiate study CAIN457A2325 for registration purposes. 
The risk to subjects in this trial will be minimized by compliance with the eligibility criteria 
and study procedures, and close clinical monitoring 
Women of child bearing potential and sexually active males must be informed that taking the 
study treatment may involve unknown risks to the fetus if pregnancy were to occur during the 
study, and agree that in order to participate in the study they must adhere to the contraception 
requirements outlined in the exclusion criteria. If there is any question that the subject will not 
reliably comply, they should not be entered or continue in the study. 
 
5 
Population 
Approximately 120 subjects with moderate to severe plaque psoriasis will be randomized in 
approximately 30 centers worldwide. Approximately 150 subjects are expected to be screened 
to provide the number of randomized subjects. Drop-outs after randomization will not be 
replaced. 


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5.1 
Inclusion criteria 
Subjects eligible for inclusion in this study must meet 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 
5.2 
Exclusion criteria 
Subjects meeting 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 (eg, 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. Subjects not willing to limit Ultraviolet (UV) light exposure (eg, 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 human 
chorionic gonadotropin (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 (eg, 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 (eg, 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). For female subjects on the 
study, 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, (estrogen and progesterone), injected or implanted hormonal methods of 
contraception or other forms of hormonal contraception that have comparable efficacy 
(failure rate < 1%), for example hormone vaginal ring or transdermal hormone 
contraception or placement of an intrauterine device or intrauterine system. 
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. 
In case local regulations deviate from the contraception methods listed above, local regulations 
apply and will be described in the Informed Consent Form (ICF). 
Women are considered post-menopausal and not of child bearing potential if they have had 12 
months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age 
appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with 
or without hysterectomy), total 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 


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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 : 
• Significant medical problems, including but not limited to the following: uncontrolled 
hypertension (repeated values of systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 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 
(TB) infection as defined by a positive central laboratory test result at screening. Subjects 
with a positive test result may participate in the study if further work up (according to local 
practice/guidelines) 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 country guidelines prior to randomization. 
12. Past medical history record or current infection with Human Immunodeficiency Virus, 
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 (eg, because of poor tolerability 
or lack of access to veins) or to self-administer sub-cutaneous injections. 
15. History or evidence of ongoing alcohol or drug abuse, within the last six months before 
Randomization. 
16. History of hypersensitivity to any of the study treatments or its excipients or to drugs of 
similar chemical classes. 
 
6 
Treatment 
6.1 
Study treatment 
6.1.1 
Investigational and control drugs 
Novartis will supply the following study drugs with the same liquid formulation: 
 
Investigational treatment: 
• 
Secukinumab 300 mg, provided as one 2 mL auto-injector (AI) 


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Control treatment: 
• 
Secukinumab 300 mg, provided as two 1 mL pre-filled syringes (PFS) containing 150 mg 
secukinumab 
• 
Secukinumab placebo, provided as either one 2 mL AI or two 1 mL PFS 
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. 
The removable cap of the secukinumab PFS 1 mL form only contains a derivative of natural 
rubber latex (note: this is not applicable to the 2 mL AI). Although no natural rubber latex is 
detected in the cap, the safe use of the secukinumab 1 mL PFS in latex-sensitive individuals has 
not been studied. 
 
6.1.2 
Additional study treatments 
No other treatment beyond investigational drug and control drug are included in this trial. 
 
6.1.3 
Treatment arms/group 
Subjects will be randomized using a 2:2:1:1 ratio into one of the following 4 treatment arms. 
In order to achieve a balanced weight distribution in each treatment arm, randomization will be 
stratified by body weight at baseline, < 90 kg or ≥ 90 kg. 
• Group 1: Secukinumab 300 mg (2 mL AI) 
• Group 2: Secukinumab 300 mg (2 x 1 mL PFS) 
• Group 3: Placebo - Secukinumab 300 mg (2 mL AI) 
• Group 4: Placebo - Secukinumab 300 mg (2 x 1 mL PFS) 
During Treatment Period 1, subjects will self-administer three injections of study treatment at 
study sites (Table 8-1) once weekly at Randomization, Weeks 1, 2, and 3, followed by dosing 
at Week 4 and Week 8: 
• Group 1: one 2 mL secukinumab 300 mg AI plus two 1 mL PFS matching placebo 
secukinumab s.c. injections 
• Group 2: two 1 mL secukinumab 150 mg PFS plus one 2 mL AI matching placebo 
secukinumab s.c. injections 
• Group 3 and Group 4: will receive placebo treatment administered as two 1 mL placebo 
secukinumab 150 mg PFS plus one 2 mL AI matching placebo secukinumab s.c. injections 
The treatment of the 2 placebo groups will be the same during treatment Period 1 and will only 
differ after Week 12 in treatment period 2 for non-responders only. 
Prior to administration of the Week 12 dose, PASI 90 response status will be evaluated and 
subjects classified accordingly. Based on the PASI 90 responders status (per definition in 
Section 8.3.2) at the Week 12 visit, subjects on placebo will either remain on placebo during 
the Treatment Period 2 or be re-assigned to secukinumab 300 mg treatment. 
The 2 placebo groups will be considered as a single placebo arm for analysis purpose (up to 
Week 12). 


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During Treatment Period 2, subjects will self-administer three injections of study treatment at 
study sites or at home (Table 8-1) every four weeks starting at Week 12 up to Week 48: 
• Group 1: one 2 mL secukinumab 300 mg AI plus two 1 mL PFS matching placebo 
secukinumab s.c. injections 
• Group 2: two 1 mL secukinumab 150 mg PFS plus one 2 mL AI matching placebo 
secukinumab s.c. injections 
• Group 3 and Group 4 (on placebo during Treatment Period 1): 
1. PASI 90 non-responders of Group 3: one 2 mL secukinumab 300 mg AI plus two 1 
mL PFS matching placebo secukinumab s.c. injections 
2. PASI 90 non-responders of Group 4: two 1 mL secukinumab 150 mg PFS plus one 2 
mL AI matching placebo secukinumab s.c. injections 
3. PASI 90 responders of Group 3 and Group 4: will continue to receive the same 
placebo treatment administered as two 1 mL placebo secukinumab 150 mg PFS plus 
one 2 mL AI matching placebo secukinumab s.c. injections. 
 
In addition, subjects will self-administer three injections of study treatment at study sites 
(Table 8-1) once weekly at Weeks 13, 14 and 15: 
• PASI 90 non-responders of placebo Group 3: one 2 mL secukinumab 300 mg AI plus 
two 1 mL PFS matching placebo secukinumab s.c. injections 
• PASI 90 non-responders of Placebo Group 4: two 1 mL secukinumab 150 mg PFS 
plus one 2 mL AI matching placebo secukinumab s.c. injections 
• Group 1, Group 2 and PASI 90 responders of Placebo Group 3 and Group 4: two 1 
mL placebo secukinumab 150 mg PFS plus one 2 mL AI matching placebo 
secukinumab s.c. injections. 
 
 
6.1.4 
Treatment duration 
The planned duration of treatment is 52 weeks. Subjects may be discontinued from treatment 
earlier at the discretion of the investigator or the subject 
 
6.2 
Other treatment(s) 
No additional treatment beyond investigational drug and control drug are included in this trial 
 
6.2.1 
Concomitant therapy 
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 on the appropriate Case Report 
Forms. 
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 appropriate Case Report Forms and should be avoided 


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during the 12 hours preceding a scheduled visit. Use of any other non-medicated interventions 
should be recorded on the appropriate Case Report Forms. 
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication. If in doubt the investigator should contact the Novartis medical monitor before 
randomizing a subject or allowing a new medication to be started. 
Any treatment known to worsen psoriasis (eg, beta-blockers, calcium channel blockers, lithium) 
should be stable at least 4 weeks before randomization. 
 
6.2.2 
Prohibited medication 
Use of any treatments displayed in Table 6-1 that could confound the efficacy of the 
investigational drug is NOT allowed during the study for any indication. All prohibited 
treatments should be washed out as shown in Table 6-1. 
The investigator should instruct the subject to notify the study site about any new treatments. 
At the discretion of the investigator, if any use of a prohibited treatment presents an undue 
safety risk for the subject, the study treatment must be discontinued. If a live vaccination has to 
be administered, the study treatment must be discontinued. 
 
Table 6-1 
Prohibited medication 
Prohibited treatments1, 2 
Washout 
period 
(before 
randomization) 
 
 
Note 
1 If a prohibited treatment of psoriasis is used during the 
study, the subject should discontinue use of the 
prohibited treatment if he/she wishes to continue in the 
study. 
2 In case of undue safety risk for the subject, the subject 
should discontinue study treatment at the discretion of 
the investigator. 
Alefacept, briakinumab, 
efalizumab, ustekinumab 
 
Etanercept 
24 weeks 
 
4 weeks 
 
Biological immunomodulating 
agents other than above 
(eg, adalimumab, infliximab) 
Other systemic immunomodulating 
treatments 
(eg, Methotrexate, cyclosporine A, 
corticosteroids, cyclophosphamide) 
Other systemic psoriasis 
treatments (eg, retinoids, 
fumarates, apremilast) 
Photochemotherapy (eg, psoralen 
and ultraviolet A (PUVA)) 
12 weeks 
 
 
4 weeks 
 
 
 
4 weeks 
 
 
4 weeks 
Phototherapy (e.g., UVA, UVB) 
2 weeks 
 


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Prohibited treatments1, 2 
Washout 
period 
(before 
randomization) 
Note 
1 If a prohibited treatment of psoriasis is used during the 
study, the subject should discontinue use of the 
prohibited treatment if he/she wishes to continue in the 
study. 
2 In case of undue safety risk for the subject, the subject 
should discontinue study treatment at the discretion of 
the investigator. 
Topical treatment3,4,5 that is likely to 
impact signs and symptoms of 
psoriasis (eg, corticosteroids [CS], 
vitamin D analogues, 
pimecrolimus, tacrolimus, retinoids, 
salicylvaseline, salicylic acid, lactic 
acid, tar, urea, -hydroxy or fruit 
acids) 
2 weeks 
3 Including intra-articular or peri-articular injections. Note 
that inhaled corticosteroids as well as corticosteroid 
drops in the eye or ear or nasal sprays are permitted. 
4 Mild to moderate topical corticosteroids are allowed 
only during the screening period if used only on the face, 
scalp, hands and feet and/or genitoanal area and if not 
used during the 12 h preceding the randomization visit. 
5 Topical corticosteroids and other topical treatments will 
be allowed during treatment period 2 only if (all must 
apply): 
•medication is started after the Week 12 visit was 
completed; 
•medication is used for 14 consecutive calendar days or 
less; 
•medication is used for an indication other than psoriasis 
and not on the area affected with psoriasis. 
Live vaccinations6 
6 weeks 
6 If the subject received a live vaccination during the 
study, the subject must discontinue study treatment. 
 
Any investigational treatment or 
participation in any interventional 
trial 
4 weeks or 5 
half-lives 
(whichever is 
longer) 
 
 
There is no restriction on the use of anti-histamines and on the use of topical corticosteroids in the 
eye, nose or ear. 
UVA and UVB: Ultra Violet rays A and B 
 
 
Exposure to light 
Exposure to UV light (including sunbathing and/or use of UV tanning devices) should be limited 
to avoid possible effect on psoriasis. 
 
6.2.3 
Rescue medication 
Use of rescue medication is not permitted in this study 
 
6.3 
Subject numbering, treatment assignment, randomization 
6.3.1 
Subject numbering 
Each subject is identified in the study by a Subject Number (Subject No.), that is assigned when 
the subject is first enrolled for screening and is retained as the primary identifier for the subject 
throughout his/her entire participation in the trial. The Subject No. consists of the Center 
Number (Center No.) (as assigned by Novartis to the investigative site) with a sequential subject 
number suffixed to it, so that each subject is numbered uniquely across the entire database. 


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Upon signing the informed consent form, the subject is assigned to the next sequential Subject 
No. available. 
If a subject is re-screened for the study, then he/she must sign a new ICF and be issued a new 
Subject Number prior to any assessment being conducted for the subject under the new Subject 
Number 
 
6.3.2 
Treatment assignment, randomization 
At Randomization visit, all eligible subjects will be randomized via Interactive Response 
Technology (IRT) to one of the treatment arms. No re-randomization will be done at Week 12 
as the original randomization is already including the Period 2 treatment group to be assigned 
to for Non-responders of the placebo arm. 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 one 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 subject. 
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 
Global Clinical Supplies 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 should be recorded on the appropriate Case Report Forms. 
Randomization will be stratified by body weight assessed at baseline. Stratification ensures a 
balanced allocation of subjects to treatment groups within the two weight strata: “body weight 
< 90 kg” or “body weight ≥ 90 kg”. 
The randomization scheme for subjects will be reviewed and approved by a member of the 
Randomization Office. 
 
6.4 
Treatment blinding 
A double-dummy design is used to ensure that the identity of the study drug cannot be disguised, 
as the drug products are visibly different. 
Subjects, investigator staff and persons performing the assessments, and data analysts will 
remain blind to the identity of the study treatment from the time of randomization until the end 
of study database lock, 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 with the following exceptions: 
• 
Specific vendors whose role in trial conduct requires their unblinding (eg, IRT) 
• 
Global Clinical Supplies 


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• 
The designated Novartis study team members involved in the primary endpoint analysis, 
as described in Section 4.4. 
2. 
The identity of the treatments will be concealed by the use of investigational treatments 
that are all identical in packaging, labeling, schedule of administration, appearance, taste and 
odor. 
Unblinding will only occur in the case of subject emergencies, at the time of the endpoint 
analysis as described below. The blind will be kept until the final 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 6.6.2). 
 
6.5 
Dose escalation and dose modification 
Study treatment dose adjustments and/or interruptions are not permitted. However a positive 
urine pregnancy test during the study requires immediate interruption of study treatment until 
serum pregnancy test is performed and found to be negative. If the serum test is positive, study 
treatment must be permanently discontinued. 
 
6.5.1 
Follow-up for toxicities 
Not applicable. 
 
6.6 
Additional treatment guidance 
6.6.1 
Treatment compliance 
All doses of study treatment administration will be recorded on the appropriate case report 
form. 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 and empty medication 
boxes/outer packing/devices should be collected (as permitted by local regulations) for 
compliance checks by field monitors. 
 
6.6.2 
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 
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 a fax or email confirming this information. The system will 


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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) 
• subject number 
In addition, oral and written information to the subject must be provided on how to contact 
his/her back-up in cases of emergency, or when he/she is unavailable, to ensure that un-blinding 
can be performed at any time. 
 
6.7 
Preparation and dispensation 
Each study site will be supplied with study drug in packaging as described under investigational 
and control drugs section. 
A unique medication number is printed on the study medication label. 
Investigator staff will identify the study medication kits to dispense to the subject by contacting 
the IRT and obtaining the medication number(s). The study medication has a 2-part label (base 
plus tear-off label), immediately before dispensing the medication kit to the subject, site 
personnel will detach the outer part of the label from the packaging and affix it to the source 
document. 
 
6.7.1 
Handling of study treatment and additional treatment 
 
6.7.1.1 
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 designated 
site personnel 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 CO 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. Subjects will be asked 
to return all unused study treatment and packaging at the end of the study or at the time of 
discontinuation of study treatment. 
The subjects will record the date(s) of administration at home on a diary/form and will return 
the used medication and packaging at their next visit to the site. Subjects will be asked to return 
all unused medication and packaging the latest at the completion of the study or at the time of 


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discontinuation of the investigational treatment. Site staff will record in the appropriate 
documents the dates of the administration. Detailed instructions will be provided separately. 
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 to the Novartis monitor or to the Novartis address provided in the investigator 
folder at each site. 
 
6.7.1.2 
Handling of additional treatment 
Not applicable. 
 
6.7.2 
Instruction for prescribing and taking study treatment 
All doses of study treatment (secukinumab and/or placebo) will be self-administered by the 
subject either at the study site or at home. 
The first use at Randomization and the Visit 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 by the site staff walking them through 
the Instructions For Use (IFU) on how to self-inject via the PFS and AI (the 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 and auto-injector). At Randomization and 
Week 1, site staff will observe and complete the self-injection assessment checklist (Table 8-5) 
and the possible hazard assessment check list (Table 8-6) for the 2 mL auto-injector. 
Home administrations should be done at pre-defined visits (Table 8-1) and can be performed 
by the subject. If self-administration is not chosen, these administrations can be performed by 
a 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 site 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 
All doses of study treatment that are administered at the study site should be performed after 
the study assessments for the visit, including blood sampling and the completion of DLQI 
questionnaire by the subjects, have been completed. 
The first study treatment administration will occur at the Randomization/baseline Visit, after 
all study scheduled assessments have been performed (and inclusion/exclusion criteria 
confirmed) and only after the scheduled blood samples have been drawn. 


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The study treatment solutions must be self-injected subcutaneously in non-affected areas of the 
skin starting with the 2 mL AI, the 2 injections of 1 mL PFS taking place subsequently, after 
completion of the SIAQ, when applicable. Administration of study treatment may vary on the 
body regions, i.e., changing the injection site from visit to visit: right thigh, left thigh, right 
stomach, left stomach, upper outer arm (when assisted by attendant), whilst separating the 2 mL 
AI and the two 1 mL PFS injection sites. Used syringes and AI should be disposed immediately 
after use in a sharps container or according to the regulatory needs of the respective countries. 
More information can be found in the study-specific IFU. 
All dates and times of injections during the study must be recorded on the appropriate CRF. 
All kits of study treatment assigned by the IRT will be recorded/databased in the IRT. 
The investigator must promote compliance by instructing the subject to take the study treatment 
exactly as prescribed and by stating that compliance is necessary for the subject’s safety and 
the validity of the study. The subject must also be instructed to contact the investigator if he/she 
is unable for any reason to take the study treatment as prescribed. 
 
7 
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. 
If applicable, in cases where the subject's representative(s) gives consent (if allowed according 
to local requirements), 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 agreement by 
personally signing and dating the written informed consent document. 
Informed consent must be obtained before conducting any study-specific procedures (eg, 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 International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines and regulatory 
requirements and is considered appropriate for this study. Any changes to the proposed consent 
form suggested by the investigator must be agreed by Novartis before submission to the 
IRB/IEC. 
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 investigational drug 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 then must be discussed with the subject. 
Women of child bearing potential must be informed that taking the study treatment may involve 
unknown risks to the fetus if pregnancy were to occur during the study and agree that in order 
to participate in the study they must adhere to the contraception requirements. 


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Subjects might be asked to complete an optional questionnaire to provide feedback on their 
clinical trial experience. 
A copy of the approved version of all consent forms must be provided to Novartis/sponsor after 
IRB/IEC approval. 
 
8 
Visit schedule and assessments 
Assessment schedule lists all of the assessments and when they are performed. All data obtained 
from these assessments must be supported in the subject’s source documentation. 
Subjects should be seen for all visits as outlined in the assessment schedule or as close to the 
designated day/time as possible. Every effort should be made to respect the timeframe for all 
visits and particularly when 
. Missed or rescheduled visits should not 
lead to automatic discontinuation. Subjects who prematurely discontinue the study for any 
reason should be scheduled for the final visit as soon as possible at which time all of the 
assessments listed for the final visit will be performed. At this final visit, all dispensed 
investigational product should be reconciled, and the adverse events and concomitant 
medications recorded on the CRF. 
For subjects who discontinue study treatment prematurely for any reason other than withdrawal 
of informed consent or loss to follow-up procedures as described in Section 9 should be 
followed. 
During Treatment Periods 1 and 2, subjects may be seen at an unscheduled visit, eg, 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 8-1 is as follows (may vary depending 
on different type of visits): 
Investigator / Qualified Site Staff 
1. IGA mod 2011 
2. PASI 
3. Other procedures 
• All remaining study visit procedures (eg, laboratory and 
 
 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 EOT1 Visit Week 12. 
• Contact IRT to register the subject visit. 
• Prepare the corresponding study medication packs as indicated in the study-specific 
IFU brochure (dispense for home administrations, as required). 
• Provide guidance to subjects for self-administration prior to the first treatment 
administration (Section 6.7.2) at Randomization; from Visit Week 1 until End of 
Treatment Period 2 subjects should refer to the IFU and proceed with self- 


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administrations either at the site or they receive instructions for sub-sequent home 
administrations. 
• Auto-injector usability and hazard assessment should be done by site personnel, at 
Randomization Visit and at Visit Week 1 while the injections with the 2 mL AI are 
self-administered by the subject prior to the 1 mL PFS injection. 
 
Subjects 
• Subjects must complete the DLQI prior to any investigator assessments. 
• SIAQ PRE module must be completed once at Randomization prior to the first injection with 
the 2 mL AI. 
• SIAQ POST module, must be completed after the injections with the 2 mL AI as shown in 
Table 8-1. 
The 1 mL PFS injection should follow the SIAQ POST. 


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Table 8-1 
Assessment schedule 
 
Period 
Scree 
Treatment Period 1 
Treatment Period 2 
U 
ning 
Week (relative to 
Randomization) 
≤ -4 
Rg 
1 
2 
3 
4 
8 
12a 
EOT1 
13 
14 
15 
16 
20i 
24i 
28 
32i 
36i 
40 
44i 
48i 
52b 
EOT2/ 
EOS 
Day 
≥ -28 
to 
R 
8 
15 
22 
29 
57 
85 
92 
99 
106 
113 
141 
169 
197 
225 
253 
281 
309 
337 
365 
≤ -7 
Obtain informed consent* 
X 
Demographics 
X 
Inclusion/exclusion criteriac 
S 
S 
Smoking history 
X 
Psoriasis medical history 
X 
Previous psoriasis 
therapies 
X 
Cardiovascular medical 
history 
X 
Other medical history 
X 
Prior or Concomitant non- 
drug therapies/procedures 
Update as necessary 
Concomitant medicationsh 
Update as necessary 
Physical Examc 
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 
Lab analysis: safety paneld 
(Hematology and 
chemistry) 
X 
X 
X 
X 
X 
X 
X 
X 
Fasting labs: glucose, lipid 
paneld 
X 


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Period 
Scree 
Treatment Period 1 
Treatment Period 2 
U 
ning 
Week (relative to 
Randomization) 
≤ -4 
Rg 
1 
2 
3 
4 
8 
12a 
EOT1 
13 
14 
15 
16 
20i 
24i 
28 
32i 
36i 
40 
44i 
48i 
52b 
EOT2/ 
EOS 
Day 
≥ -28 
to 
R 
8 
15 
22 
29 
57 
85 
92 
99 
106 
113 
141 
169 
197 
225 
253 
281 
309 
337 
365 
≤ -7 
Urinalysis (local) 
S 
S 
Tuberculosis testd 
X 
X 
Serum pregnancy testd,e 
X 
Urine pregnancy test 
(local)e 
S 
X 
X 
ECG (standard 12 lead)c 
S 
PASI 
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 
DLQI 
X 
X 
X 
X 
X 
SIAQf 
X 
X 
X 
X 
X 
X 
Usability and hazard 
assessment 
X 
X 
AE/SAE assessmenth 
Update as necessary 
Self-injection of study 
treatment at site 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Self-injection of study 
treatment at Homeh 
X 
X 
X 
X 
X 
X 
Randomization by IRTi 
X 
Contact IRT for drug 
assignmenta 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Period 
Scree 
ning 
Treatment Period 1 
Treatment Period 2 
U 
Week (relative to 
Randomization) 
≤ -4 
Rg 
1 
2 
3 
4 
8 
12a 
EOT1 
13 
14 
15 
16 
20i 
24i 
28 
32i 
36i 
40 
44i 
48i 
52b 
EOT2/ 
EOS 
Day 
≥ -28 
to 
≤ -7 
R 
8 
15 
22 
29 
57 
85 
92 
99 
106 
113 
141 
169 
197 
225 
253 
281 
309 
337 
365 
Disposition (EOT1 
/EOT2/EOS completion) 
X 
AE = adverse event, BSA = Body Surface Area, DLQI = Dermatology Life Quality Index, eCRF = electronic case report form, , R = randomization, S = 
assessment to be recorded in the source documentation only, U = unscheduled visits - assessments performed at unscheduled visits are at investigator’s 
discretion 
U = assessment to be recorded in the clinical database or received electronically from a vendor 
*Informed consent obtained prior to all study specific screening procedures 
a During Visit Week 12, subjects will have their last assessments performed for the Treatment Period 1 prior to the dose. 
b EOT1 or EOT2/EOS must be completed for treatment discontinuations from Treatment Period 1 or 2, respectively. 
c Data regarding to which inclusion/exclusion criteria are not met are captured on the appropriate eCRF. 
d Samples will be shipped to and analyzed by the central laboratory. The Tuberculosis test may be repeated if the result is “indeterminate”, this is performed 
during the Screening Period. 
e 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. 
f SIAQ PRE module only at Randomization, SIAQ POST module for all SIAQ time points after 2 mL AI injection 
g The PASI Score and IGA mod 2011 will be calculated by the PI to confirm the subject eligibility based on IGA mod 2011, PASI and BSA. At Visit Week 12 
(EOT1), the site will calculate the PASI 90 responder status. Both will be entered in IRT and in the eCRF. 
h During home administrations, adverse events that may occur as well as concomitant medication should be collected by the investigator and reported in the 
eCRF. 
i Study treatment will be self-administered at home at Weeks 20, 24, 32, 36, 44, and 48, and at study site for all other visits. 


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8.1 
Screening 
Screening 
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 is re-screened for the study, then the subject must sign a new ICF and be issued a 
new Subject Number prior to any assessment being conducted for the subject under the new 
Subject Number. The investigator/qualified site staff will record if the subject was re-screened 
on the re-screening section of the 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 appropriate eCRF page 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 (including any chest x-ray), if applicable, if performed not more 
than 12 weeks before randomization. 
 
8.1.1 
Information to be collected on screening failures 
Subjects who sign the ICF and discontinue prior to randomization at the Randomization Visit 
are considered screening failures. IRT must be notified within five days and the reason for not 
being randomized will be entered in the appropriate eCRF page. The Screening Visit date, the 
Demography, Informed Consent, and Inclusion/Exclusion Criteria eCRF sections should be 
completed. The Adverse Event eCRF section and a SAE Form should be completed for any 
SAE that occurred during the Screening Period. Adverse events that are not SAEs will be 
followed by the investigator and collected only in the source data. The Withdrawal of consent 
eCRF section should be completed if consent was withdrawn prior to the randomization. 
 
8.2 
Subject demographics/other baseline characteristics 
Country specific regulations should be considered for the collection of demographic and 
baseline characteristics in alignment with CRF 
 
8.2.1 
Demographics 
Subject demographic data will include: age (in years), sex, race, ethnicity, and child-bearing 
potential (for females only). 
 
8.2.2 
Psoriasis medical history/previous psoriasis therapies 
The following information should be collected and entered in the eCRF section 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, eg: 
• Generalized pustular or pustular palmoplantar psoriasis 
• Guttate, palmoplantar, nail, inverse, scalp or erythrodermic psoriasis 


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• 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 
8.2.3 
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. 
 
8.2.4 
Cardiovascular medical history 
Any information pertaining to cardiovascular medical history assessed prior to randomization 
should be recorded on the appropriate case report form. 
 
8.2.5 
Medical history 
Relevant medical history and current medical conditions present before signing the informed 
consent should be recorded on the appropriate eCRF section. 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 sections, see above. 
 
8.2.6 
Determination of the tuberculosis status 
Determination of the 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. Any significant findings should be recorded on the appropriate eCRF page 
(Tuberculosis assessment or medical history as deemed necessary) (See Appendix 6 for more 
details). 
 
8.3 
Efficacy 
The following order should be applied when performing the efficacy assessments at study 
visits: 
• IGA mod 2011 
• PASI 
8.3.1 
Investigator’s Global Assessment (IGA mod 2011) 
It is recommended that the same evaluator conduct the assessment 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 Randomization or at a previous visit. 
The IGA mod 2011 score will be recorded in the eCRF. 


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Table 8-2 
The IGA mod 2011 rating scale 
Score Short 
Description 
Detailed Description 
 
0 
Clear 
No signs of psoriasis. Post-inflammatory hyperpigmentation may be 
present. 
1 
Almost clear 
Normal to pink coloration of lesions; no thickening; no to minimal focal 
scaling. 
2 
Mild 
Pink to light red coloration; just detectable to mild thickening; 
predominantly fine scaling. 
3 
Moderate 
Dull bright red, clearly distinguishable erythema; clearly distinguishable 
to moderate thickening; moderate scaling. 
4 
Severe 
Bright to deep dark red coloration; severe thickening with hard edges; 
severe/coarse scaling covering almost all or all lesions. 
Note: Involvement of nails is not part of the assessment 
 
 
Based on this scale, 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. 
 
8.3.2 
Assessment of total Body Surface Area (BSA) and Psoriasis Area 
Severity Index (PASI) 
The investigator or qualified designee will complete the PASI assessment. 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 as first step of PASI 
calculation from the percentages of areas affected, including head, trunk, upper limbs and lower 
limbs (see Table 8-3). The following calculations will be done: each reported percentage will 
be multiplied by its respective body region corresponding factor (head = 0.1, trunk = 0.3, upper 
limbs = 0.2, lower limbs = 0.4). The resulting 4 percentages will be added up to estimate the 
total BSA affected by 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 8-3. 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. 


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The buttocks are assessed as part of the lower limbs. 
When scoring the severity of erythema, scales should not be removed. 
 
Table 8-3 
The PASI scoring system 
Body region 
Erythema (E) 
Thickening (I) 
Scaling (D) 
Area score (A) 
(plaque 
elevation, 
induration) 
(desquamation) (based on true 
area %)* 
Head (H)† 
0 = none 
0 = none 
0 = none 
0 = no involvement 
1 = slight 
1 = slight 
1 = slight 
1 = > 0 - < 10 
2 = moderate 
2 = moderate 
2 = moderate 
2 = 10 - < 30 
3 = severe 
3 = severe 
3 = severe 
3 = 30 - < 50 
4 = very severe 
4 = very 
severe 
4 = very severe 
4 = 50 - < 70 
5 = 70 - < 90 
6 = 90 - 100 
Trunk (T)‡ 
0 = none 
0 = none 
0 = none 
0 = no involvement 
1 = slight 
1 = slight 
1 = slight 
1 = > 0 - < 10 
2 = moderate 
2 = moderate 
2 = moderate 
2 = 10 - < 30 
3 = severe 
3 = severe 
3 = severe 
3 = 30 - < 50 
4 = very severe 
4 = very 
severe 
4 = very severe 
4 = 50 - < 70 
5 = 70 - < 90 
6 = 90 - 100 
Upper limbs 
(U) 
0 = none 
0 = none 
0 = none 
0 = no involvement 
1 = slight 
1 = slight 
1 = slight 
1 = > 0 - < 10 
2 = moderate 
2 = moderate 
2 = moderate 
2 = 10 - < 30 
3 = severe 
3 = severe 
3 = severe 
3 = 30 - < 50 
4 = very severe 
4 = very 
severe 
4 = very severe 
4 = 50 - < 70 
5 = 70 - < 90 
6 = 90 - 100 
Lower limb 
(L)§ 
0 = none 
0 = none 
0 = none 
0 = no involvement 
1 = slight 
1 = slight 
1 = slight 
1 = > 0 - < 10 
2 = moderate 
2 = moderate 
2 = moderate 
2 = 10 - < 30 
3 = severe 
3 = severe 
3 = severe 
3 = 30 - < 50 
4 = very severe 
4 = very 
severe 
4 = very severe 
4 = 50 - < 70 
5 = 70 - < 90 
6 = 90 - 100 
* 
Percentage (not score) of body region (not whole body) affected will be entered in the eCRF. 
† Neck is assessed as part of the Head (H) body region. 


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‡ 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. 
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) 
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 8-3. 
The definitions used in this study are based on Committee for Medicinal Products for Human 
Use (CHMP) guidelines for psoriasis (CHMP/EWP/2454/02 2004). 
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 Period 
1, at Visit week 12. 
 
8.3.3 
Appropriateness of efficacy assessments 
PASI scores outcome measures, the assessment of the severity of the psoriasis symptoms and 
the extent to which the subject’s body area is affected by the disease, is mandated by the 
European Medicines Agency (EMA) for the clinical investigation of medicinal products for the 
treatment of psoriasis (CHMP/EWP/2454/02 2004). 
As indicated in Section 8.3.1, the IGA mod 2011 scale has been developed by Novartis in 
collaboration with Health Authorities, in particular the US FDA (Langley et al 2015). It has 
been used in phase III, IIIb, and IV secukinumab 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. 
 
 
8.4 
Safety/Tolerability 
Safety assessments are specified below with the assessment schedule detailing when each 
assessment is to be performed. 
Blood withdrawals and safety assessments should be done prior to study treatment 
administration and should be taken as shown in Table 8-1 and in Appendix 2. 


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Appropriate safety assessments (eg, evaluation of AEs and SAEs including injection site 
reactions) should be repeated after the dose is administered. For details on AE collection and 
reporting, refer to AE section (Section 10). 
 
Table 8-4 
Physical Assessments 
Assessment Specification 
 
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 8-1. 
If necessary, based on medical history and/or symptoms, additional exams will be 
performed at the discretion of the investigator. 
Physical 
examination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
 
 
 
 
 
 
 
 
 
 
 
 
Height and 
weight 
Whenever possible, assessments for an individual subject should be performed by 
the same member of the study site staff throughout the study. 
Information for all physical examinations must be included in the source 
documentation at the study site. Clinically relevant findings that are present prior to 
signing informed consent must be included in the Medical History part of the eCRF. 
Significant findings made after first administration of investigational drug which meet 
the definition of an AE must be recorded on the Adverse Event section of the eCRF 
Vital signs (including blood pressure and pulse measurements) will be assessed at 
every scheduled visit as indicated in Table 8-1. 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 section. 
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 bpm(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. 
Height and body weight will be measured as listed in Table 8-1. 
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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8.4.1 
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. 
Subjects should avoid smoking within the hour preceding the blood draws. 
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. 
 
8.4.1.1 
Hematology 
Hemoglobin, hematocrit, red blood cell count, white blood cell (WBC) count with differential 
(neutrophils including bands, lymphocytes, monocytes, eosinophils, basophils) and platelet 
count will be measured at all scheduled study visits, within the visit window suggested in 
Table 8-1. 
 
8.4.1.2 
Clinical chemistry 
Serum chemistry will include urea, creatinine, total bilirubin, Aspartate Aminotransferase 
AST (SGOT), Alanine Aminotransferase ALT (SGPT), Gamma-Glutamyl Transferase (GGT), 
alkaline phosphatase, sodium, potassium, bicarbonate, calcium, phosphorous, total protein, 
albumin, and uric acid. Serum chemistry will be measured at all scheduled study visits within 
the visit window specified in Table 8-1. 
 
8.4.1.3 
Fasting Laboratory evaluations 
Fasting (8 hour duration with water ad libitum) laboratory evaluations will be assessed as 
indicated in Table 8-1. 
Subjects should avoid smoking within the hour preceding the blood draws. 
 
8.4.1.3.1 Plasma glucose 
Fasting blood sample will be collected for measuring fasting plasma glucose as indicated in 
Table 8-1. 
 
8.4.1.3.2 Lipid panel 
A lipid profile including High Density Lipoprotein, Low Density Lipoprotein, cholesterol, 
triglycerides, will be measured from a fasting blood sample as indicated in Table 8-1. 


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8.4.1.4 
Urinalysis 
Dipsticks will be provided to the study sites for local urinalysis assessments. The sites will 
record the results in the appropriate CRF for each subject. Standard dipstick measurements for 
specific gravity, protein, glucose, pH, blood, urine blood dipstick (non-hemolyzed), urine blood 
dipstick (hemolyzed), bilirubin, ketones and WBC will be done as indicated in Table 8-1. 
If needed conditional microscopy assessments will be performed. 
Documentation related to urinalysis including results must be included in the source 
documentation at the study site. Clinically relevant findings that are present prior to signing 
informed consent must be included on appropriate eCRF page. Significant findings made after 
first administration of investigational drug which meet the definition of an AE must be recorded 
on the appropriate eCRF page. 
8.4.2 
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. 
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 


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collection first, followed by vital signs, and blood sampling. The Fridericia QT correction 
formula 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 CRF 
capturing medical history/ Current medical conditions/AE as appropriate. 
 
8.4.3 
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 8-1. 
Any woman with a confirmed positive pregnancy test during Screening is not eligible for 
randomization. A positive urine pregnancy test during the treatment periods of the study 
requires immediate interruption of study treatment until a serum β-hCG (Human Chorionic 
Gonadotropin) 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. 
 
8.4.4 
Appropriateness of safety measurements 
The safety assessments selected are standard measures for a biologic immunomodulating agent 
in Psoriasis. 
 
8.5 
Additional assessments 
The following additional assessments will be performed: 
• Clinician Reported Outcomes (ClinRO) 
• Usability and hazard assessment of the auto-injector 
• Patient Reported Outcomes (PRO) 
• SIAQ 
• DLQI 
• 
 
8.5.1 
Clinical Outcome Assessments (COAs) 
Clinician Reported Outcomes (ClinRO) 
Usability and hazard assessment of the auto-injector 
The goal is to measure and evaluate the usability of the auto-injector during observed use, as 
well as the assessment of the hazards with the auto-injector. 
Subjects will be instructed at Randomization through the site staff on how to self-inject via AI 
(and PFS) following the IFU. After explanations/instructions, the injection will be self- 


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administered by the subject into the appropriate injection site of the body. The delivery of the 
dose with the 2mL AI will be observed by investigator/site staff based on the 2 assessment 
check lists (see Table 8-5 and Table 8-6) at Randomization and Visit Week 1. Assessment of 
possible administration hazards will be based on identified hazards list (Table 8-6) as well as 
non-directed querying for any observed problems during self-injection. 
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 IFU on how to self-inject via AI (and PFS). 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 self-injections at the respective visits (Randomization and Week 1) site staff will 
observe and complete the 2mL self-injection assessment checklist (Table 8-5) and the possible 
hazard assessment check list (Table 8-6) for the auto-injector. 
The primary usability variables will be assessed based on binary (performed correctly: yes/no) 
response for the self-injection assessment check list. 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. 
 
Table 8-5 
Self-injection assessment check list (auto-injector) 
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 auto-injector from the outer box 
No 
P4 
Checked expiration date on auto-injector label 
No 
P5 
Inspected the auto-injector for damage 
No 
P6 
Inspected liquid for brown discoloration or particles 
No 
P7 
Removed cap from auto-injector 
Yes 
P8 
Discarded cap 
No 
P9 
Hold the auto-injector at correct angle to the injection site 
Yes 
P10 
Press the auto-injector firmly against the skin to trigger the injection 
(1st Click), and keep holding the auto-injector firmly against the skin 
P11 
Wait until the injection is complete, confirmed by the 2nd “click” 
and/or a check that the yellow indicator fills the window 
Yes 
Yes 
P12 
The auto-injector can now be removed 
No 
P13 
Check again that the yellow indicator fills the window 
No 
P14 
Disposed used auto-injector in a sharps container 
No 


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Table 8-6 
Possible hazard assessment check list (auto-injector) 
No. 
Possible Use-related hazards 
H1 
Was there a needle stick in a critical area (eg, 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? 
H8 
Was any other problem observed?3 
H9 
Was less than the full dose administered?4 
The following potential hazards from the Hazards Identified List ([AIN457_HID_Delta225-01]) have not 
been included as not being observable during self-injection observation: microbiological 
contamination, wrong drug, transfer of transmissible diseases. 
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 (eg, 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, eg, 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 auto-injector 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 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 auto-injector 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, 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. 


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Primary usability assessment: 
This consist of the assessment of successful 2mL AI 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 “required to be 
completed for successful administration” are identified in Table 8-5, these 4 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: 
• This consist of the assessment of 2mL AI 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 
2mL AI 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 8-5 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 
8-6) will be computed by visit. 
• This consist of the 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. 
 
8.5.1.1 
Patient Reported Outcomes (PRO) 
All subjects will complete the PRO questions via an electronic tablet. The subject should be 
given sufficient space and time to complete the questionnaires. In case of any issues with tablet 
use, which cannot be resolved within the visit time window subject can complete PRO questions 
on paper form. If subject experiences any difficulties with submission after they complete the 
PROs, the study staff should assist with submitting the PRO responses. Attempts should be 
made to collect responses to all PROs for all subjects, including from those who prematurely 
discontinue prior to the study evaluation completion visit, however, if subjects refuse to 
complete PROs, this should be documented in study source records. Subject’s refusal to 
complete study PROs are not protocol deviations. 
 
8.5.1.1.1 Self-Injection Assessment Questionnaire (SIAQ) 
The SIAQ measures the overall subject experience with subcutaneous self-injection, and to 
investigate the psychometric properties (Keininger and Coteur 2011, Appendix 4). The SIAQ 


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will be performed as a summary assessment for the auto-injector as outlined in the visit schedule 
(see Table 8-1). 
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 2 mL AI self-injections and before 
the 1 mL PFS injections at the self-injections as the visits indicated in Table 8-1, including 
Randomization. 
The PRE module includes 7 items grouped into three domains: Feelings about injections, Self- 
confidence and Satisfaction with self-injection (see Appendix 4) 
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. 
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 the 2 mL AI dosing but before the 1 mL PFS 
injection (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 8-1. 
 
8.5.1.1.2 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 DLQI. 
This questionnaire should be completed by subjects before they see the study physician 
(investigator or designee) who will perform the investigator assessments. 
It will be completed in the language the respondent is most familiar with. The subject should 
be given sufficient space and time to complete the questionnaires. The study coordinator should 
check it 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 (IGA mod 2011, PASI), 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 


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10 of the protocol. Investigator should not encourage the subject to change the responses 
reported in the completed questionnaires. 
The 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 8-1. 
 
8.5.1.2 
Trial Feedback 
Not applicable. 
 
8.5.1.3 
Performance Outcomes (PerfO) 
Not applicable. 
 
8.5.1.4 
Observer Reported Outcomes (ObsRO) 
Not applicable. 
 
8.5.1.5 
Proxy Reported Outcomes 
Not applicable. 
 
 
 
 
 
 
 
 
 
 
 
 


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8.5.3 
Biomarkers 
Not applicable. 
 
8.5.4 
Other assessments 
No additional tests will be performed on subjects entered into this study. 
 
9 
Study discontinuation and completion 
9.1 
Discontinuation 
9.1.1 
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. 


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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 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. 
• 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 
participation in the study 
• Pregnancy (Section 10.1.4) 
• Ongoing use of prohibited treatment as shown in Table 6-1 
• Any situation in which study participation might result in a safety risk to the subject 
• Emergency unblinding 
If discontinuation of study treatment occurs, the investigator should make a reasonable effort 
to understand the primary reason for the subject’s premature discontinuation of study treatment 
and record this information on the appropriate eCRF page. 
Subjects who discontinue study treatment or who decide they do not wish to participate in the 
study further should NOT be considered withdrawn from the study UNLESS they withdraw 
their consent (see withdraw of informed consent section). Where possible, they should return 
for the assessments indicated in the assessment schedule. If they fail to return for these 
assessments for unknown reasons, every effort (eg, telephone, e-mail, letter) should be made to 
contact the subject/pre-designated contact as specified in the lost to follow-up section. This 
contact should preferably be done according to the study visit schedule. 
At the time of the study treatment discontinuation, 
• 
if it has been approximately 4 weeks post last dose of study treatment, then the 
assessments described in EOT1 or EOT2/EOS should be completed. 
• 
if it has not been approximately 4 weeks post last dose of study treatment, then the 
subject should be scheduled to return 4 weeks post last dose for their EOT1 
assessments or EOT2/EOS assessments. 
Assessments detailed in Table 8-1 should be completed and recorded in the eCRF. 
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. 
After study treatment discontinuation, at a minimum, in abbreviated visits, the following data 
should be collected at clinic visits or via telephone/email contact: 
• new / concomitant treatments 
• adverse events/Serious Adverse Events 


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The investigator must also contact the IRT when the subject completes EOT1 or EOT2/EOS 
visit to register the subject’s discontinuation from study treatment. 
If discontinuation occurs because treatment code has been broken, please refer to Emergency 
breaking of treatment code section. 
 
9.1.2 
Withdrawal of informed consent 
Subjects may voluntarily withdraw consent to participate in the study for any reason at any time. 
Withdrawal of consent occurs only when a subject: 
• 
Does not want to participate in the study anymore, and 
• 
Does not allow further collection of personal data 
In this situation, the investigator should make a reasonable effort (e.g. telephone, e-mail, letter) 
to understand 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 the 
assessment table. 
Novartis will continue to keep and use collected study information (including any data resulting 
from the analysis of a subject’s samples until their time of withdrawal) according to applicable 
law. 
For US and Japan: All biological samples not yet analyzed at the time of withdrawal may still 
be used for further testing/analysis in accordance with the terms of this protocol and of the 
informed consent form. 
For EU and RoW: All biological samples not yet analyzed at the time of withdrawal will no 
longer be used, unless permitted by applicable law. They will be stored according to applicable 
legal requirements 
 
9.1.3 
Lost 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 must show "due diligence" by 
documenting in the source documents steps taken to contact the subject, eg, dates of telephone 
calls, registered letters, etc. A subject should not be considered as lost to follow-up until due 
diligence has been completed or until the end of the study. 
 
9.1.4 
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 (including 


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slow enrollment), or for regulatory or medical reasons. In taking the decision to terminate, 
Novartis will always consider the subject welfare and safety. Should early termination be 
necessary, subjects must be seen as soon as possible (provide instruction for contacting the 
subject, when the subject should stop taking drug, when the subject should come for a final 
visit) 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 or sponsor depending on the local 
regulation will be responsible for informing IRBs/IECs of the early termination of the trial. 
 
9.2 
Study completion and post-study treatment 
Study completion is defined as when the last subject finishes their Study Completion visit (Visit 
Week 52), and any repeat assessments associated with this visit have been documented and 
followed-up appropriately by the Investigator, or in the event of an early study termination 
decision, the date of that decision (eg, each subject will be required to complete the study in its 
entirety and thereafter no further study treatment will be made available to them). 
 
10 
Safety monitoring and reporting 
10.1 
Definition of adverse events and reporting requirements 
10.1.1 
Adverse events 
An adverse event (AE) is any untoward medical occurrence (eg, 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. 
Novartis qualified medical personnel will be readily available to advise on trial related medical 
questions and problems. 
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 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 (Information about adverse 
drug reactions for the investigational drug can be found in the Investigator’s Brochure (IB)) 
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. 


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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 appropriate CRF capturing Adverse Events under the 
signs, symptoms or diagnosis associated with them, accompanied by the following information: 
1. 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 
2. its relationship to the study treatment (suspected: Yes / No) 
3. its duration (start and end dates) or if the event is ongoing an outcome of not 
recovered/not resolved must be reported. 
4. whether it constitutes a serious adverse event SAE – (See Section 10.1.2 for definition of 
SAE) and which seriousness criteria have been met. 
5. action taken regarding study treatment. 
All adverse events must be treated appropriately. Treatment may include one or more of 
the following: 
• Dose not changed 
• Dose Reduced/increased 
• Drug interrupted/withdrawn 
6. its outcome (not recovered/not resolved; recovered/resolved; recovered/resolved with 
sequelae; fatal; or unknown 
7. concomitant medication or non-drug therapy given 
8. subject hospitalized/subject’s hospitalization prolonged (see Section 10.1.2 for definition 
of SAE) 
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. 
 
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 CRF capturing adverse events. 
Exceptions include cases when a) a new type of psoriasis is diagnosed eg, 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 


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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 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. 
 
10.1.2 
Serious adverse events 
An 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 
• 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, eg, 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. 
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 (please refer to 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 
considered as “medically significant” 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 (please refer to Annex IV, ICH-E2D Guideline). 


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Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
 
10.1.3 
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 safety within 24 hours of learning of its occurrence. Any 
SAEs experienced after 12 week period following the last administration of study treatment 
should only be reported to Novartis safety if the investigator suspects a causal relationship to 
study treatment. 
All SAEs reported up to the subject’s last visit will be reported in the appropriate eCRF. SAEs 
beyond the last visit 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 study treatment, 
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 
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. 


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10.1.4 
Pregnancy reporting 
Pregnancies 
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. 
Pregnancy must be recorded on the Pharmacovigilance Pregnancy Form and reported by the 
investigator to the Novartis Chief Medical Office and Patient Safety (CMO & PS) 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 the pregnancy and unrelated to the pregnancy must be reported 
on a SAE form. 
 
10.1.5 
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 recorded on 
the appropriate CRF 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 within 24 hours of 
Investigator’s awareness. 
 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse 
Treatment error type 
Document in Dosing 
CRF (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 
For more information on AE and SAE definition and reporting requirements, please see the, 
respective sections. 


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10.2 
Additional Safety Monitoring 
Not applicable. 
 
11 
Data Collection and Database management 
11.1 
Data collection 
Designated investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms (eCRFs) using fully validated secure web-enabled software that conforms 
to US CFR 21 Part 11 requirements. 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 
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. 
All data should be recorded, handled and stored in a way that allows its accurate reporting, 
interpretation and verification. 
 
11.2 
Database management and quality control 
Novartis personnel (or designated Contract Research Organization (CRO) will review the data 
entered by investigational staff for completeness and accuracy. Electronic data queries stating 
the nature of the problem and requesting clarification will be created for discrepancies and 
missing values and sent to the investigational site via the EDC system. Designated investigator 
site staff is required to respond promptly to queries and to make any necessary changes to the 
data. 
Concomitant medications entered into the database will be coded using the World Health 
Organization (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). 
ECGs will be analyzed centrally and results will be sent electronically to Novartis (or a 
designated CRO). Any clinically significant findings will be reported as (cardiovascular) 
medical history or AE depending upon timing of ECG assessment compared to screening. 
Subjects will fill in their PRO data in a site based tablet. The system will be supplied by a 
vendor, who will also manage the database. The database will be sent electronically to Novartis 
personnel (or designated CRO). 


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Randomization codes and data about all study drug(s) dispensed to the subject and all dosage 
changes will be tracked using an Interactive Response Technology (IRT). The system will be 
supplied by a vendor, who will also manage the database. The data 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. 
 
11.3 
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis/ 
representative will review the protocol and data capture requirements (i.e., eCRFs) with the 
investigators and their staff. During the study, Novartis employs several methods of ensuring 
protocol and 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 data capture / data 
entry, the adherence to the protocol and to Good Clinical Practice, the progress of enrollment, 
and to ensure that study treatment is being stored, dispensed, and accounted for according to 
specifications. Key study personnel must be available to assist the field monitor during these 
visits. 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 give the monitor access to all relevant source documents to confirm their 
consistency with the data capture and/or data entry. Novartis monitoring standards require full 
verification for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional 
checks of the consistency of the source data with the CRFs are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
subjects will be disclosed. 
 
12 
Data analysis and statistical methods 
The analysis will be conducted on all subject data up to Week 16 for the week 16 interim 
analysis and on all data at the time of the trial ends for the final analysis. Any data analysis 
carried out independently by the investigator should be submitted to Novartis before publication 
or presentation. 
Treatment groups for analyses will include: 
Primary Week 12 analysis: 
• secukinumab 300 mg (2 mL AI) 
• secukinumab 300 mg (2 x 1 mL PFS) 


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• placebo 
Entire study: 
• secukinumab 300 mg (2 mL AI ) 
• secukinumab 300 mg (2 x 1 mL PFS) 
• placebo switched secukinumab 300 mg (2 mL AI ) 
• placebo switched secukinumab 300 mg (2 x 1 mL PFS) 
• any secukinumab 300 mg (2 mL AI ) 
• any secukinumab 300 mg (2 x 1 mL PFS) 
• any secukinumab 300 mg 
• placebo 
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. 
 
12.1 
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 at 
baseline visit. Unless otherwise specified, subjects with missing informed consent form as well 
as mis-randomized subjects (mis-randomized in IRT) will be excluded from the randomized set. 
(Mis-randomized 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 
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. 
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. 
 
12.2 
Subject demographics and other baseline characteristics 
Unless otherwise specified, for subject demographics and other baseline characteristics, 
analyses will be based on the randomized set. 
Demographics and baseline characteristics 
Summary statistics will be presented for continuous demographic and baseline characteristic 
variables for each treatment group and for all subjects in the randomized set. The number and 
percentage of subjects in each category will be presented for categorical variables for each 
treatment group and all subjects. 
Medical history 


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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. 
 
12.3 
Treatments 
12.3.1 
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 (eg, 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 from placebo to active treatment) or 
minimum of last dose of the treatment + 84 days and last visit date. 
 
12.3.2 
Prior and concomitant medication 
Prior and concomitant medications will be summarized by treatment group for the different 
periods 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. 
 
12.4 
Analysis of the primary variables 
Details of the testing strategy including primary endpoints are provided in Section 12.4.2. 
 
12.4.1 
Definition of primary endpoint(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 FAS. 


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12.4.2 
Statistical model, hypothesis, and method of analysis 
The co-primary endpoints of this study are PASI 75 response and IGA mod 2011 0 or 1 response 
at Week 12. 
The statistical hypothesis is that secukinumab 300 mg (2 mL AI) 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 pj denote the proportion of PASI 75 responders at Week 12 for treatment group j and rj 
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 AI) 
The following hypothesis will be tested: 
• H1: p1 − p0 ≤ 0 versus HA1: p1 − p0 > 0, 
• H2: r1 − r0 ≤ 0 versus HA2: r1 − r0 > 0 
In other words: 
H1: Secukinumab 300 mg (2 mL AI) is not superior to placebo with respect to PASI 75 
response at Week 12 
H2: Secukinumab 300 mg (2 mL AI) 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 logistic regression with treatment group (secukinumab 
2mL AI vs Placebo); baseline bodyweight strata and baseline PASI score as explanatory 
variables. Odds ratios will be computed for comparisons of secukinumab dose regimen versus 
placebo 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. 
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 (baselines PASI score), followed 
by removing categorical covariates (i.e., weight stratum etc.,); 
3. If convergence not reached, perform Fisher’s exact test. 
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 H1 and H2 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 AI) has not been 
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12.4.3 
Handling of missing values/censoring/discontinuations 
The following imputation methods will apply to the missing data: 
• Response variables based on PASI score and IGA mod 2011 categories will be imputed 
with multiple imputations (MI) method as primary imputation method. 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 (eg, 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 efficacy assessment and 
being responder consecutively at least for two preceding visits, the subject will be 
imputed as responder for the 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, or the distance between the 
scheduled visits x and x+1 is 4 weeks or less. Otherwise missing data will be imputed 
with non-response. 
 
12.4.4 
Sensitivity analyses 
Co-primary variables will be evaluated using the logistic regression as described in primary 
analysis method with non-responder imputations as sensitivity analyses. 
 
12.5 
Analysis of secondary endpoints 
The key secondary endpoint of this study is PASI 90 response at Week 12. 
Testing strategy 
As stated in Section 12.4.2, the hypotheses H1 and H2 will be included in co-primary testing 
procedure. Each hypotheses is tested at α = 2.5% (one-sided). The testing sequence will 
continue to key secondary endpoint PASI 90 at α = 2.5% (one-sided) only if both H1 and H2 
have been rejected at α (one-sided) such that a family-wise type-I-error of α (one-sided) is kept. 
H3: secukinumab 300 mg (2 mL AI) is not superior to placebo with respect to PASI 90 
response at Week 12 
PASI 90 response will be analyzed analogously to the primary endpoints at Week 12, i.e., the 
logistic regression model with treatment group, baseline bodyweight strata and baseline PASI 
score as exploratory variables. Odds ratios will be computed for comparisons of secukinumab 
versus placebo utilizing the logistic regression model fitted. 


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12.6 
Analysis of other secondary and exploratory endpoints 
12.6.1 
Efficacy 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 exact 
method. 
For PASI 50, PASI 75, PASI 90, PASI 100 and IGA mod 2011 0 or 1 response at each visit, 
comparisons between 2mL AI vs placebo and 2mL AI vs 1mL PFS x 2 will be conducted using 
logistic regression model with treatment group, body weight stratum, and baseline PASI as 
effects. 
Figures will be provided as well displaying estimates for responder rates by treatment including 
confidence intervals. 
 
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. 
 
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. 
 
12.6.2 
Safety Endpoints 
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. 
 
Adverse events 
Treatment emergent 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 


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will be counted only once with the highest severity at the system organ class level, where 
applicable. 
Tabulated summaries will be presented for Treatment Period 1 and for the entire study 
(Treatment Period 1 combined with Treatment Period 2) 
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 
periods. 
 
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 (CTC) 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). 
 
 
 
 
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). 
 
12.6.3 
Health-related Quality of Life - Dermatology Life Quality Index (DLQI) 
Summaries will be based on the FAS and will be presented separately for each treatment group. 


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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. 
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 
the two secukinumab treatment groups versus placebo. The Van-Elteren test will be performed 
at each visit. Language of the questionnaire will be the stratum 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. 
 
12.6.4 
Self-Injection Assessment 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 (Feeling about 
injections, Self-confidence domains and overall satisfaction of self-injection item) from the 
POST module taken after self-injections. Change from the PRE module to POST module in 
item and domain scores will be summarized by visit and treatment group. 
 
12.6.5 
Resource utilization 
Not applicable. 
 
 
12.6.7 
DNA 
Not applicable. 


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12.6.8 
Biomarkers 
Not applicable. 
 
 
12.7 
Interim analyses 
A Week 16 analysis will be performed when all subjects have completed the Visit Week 16. 
Additional interim analyses may be performed to support health authority interactions as 
necessary. Trial modifications are not planned based on any interim analysis. 
At the end of study, a final analysis of all data collected up to last study visit (Week 52) will be 
performed when all subjects have completed the last study visit. 
 
12.8 
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 auto-injector s.c.) 
group. 
Placebo-response rates between 3% and 7% have been reported in (Papp et al 2005, Menter et 
al 2008, Leonardi et al 2008). 
 
12.8.1 
Primary endpoint(s) 
With respect to the co-primary endpoints (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 40 subjects per group 
and assuming a response rate of 8% 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 auto-injector s.c.) group 
based on Fisher’s exact test (nQuery Advisor 7.01, two group Fisher’s-exact test of equal 
proportions) is above 99% for PASI 75 response and IGA mod 2011 0 or 1 response. 
 
12.8.2 
Secondary endpoint(s) 
The study should be sufficiently powered (above 90%) to show a response rate of 46% points 
in PASI 90 response if the placebo rate is assumed as 8%. 
 
13 
Ethical considerations and administrative procedures 
13.1 
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 


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local regulations (including European Directive 2001/20/EC, US CFR 21), and with the ethical 
principles laid down in the Declaration of Helsinki. 
 
13.2 
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 (eg, 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. 
 
13.3 
Publication of study protocol and results 
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov and 
as required in EudraCT. In addition, after study completion and finalization of the study report 
the results of this trial will be submitted for publication and posted in a publicly accessible 
database of clinical trial results, such as the Novartis clinical trial results website and all required 
Health Authority websites (eg, Clinicaltrials.gov, EudraCT etc.) 
For details on the Novartis publication policy including authorship criteria, please refer to the 
Novartis publication policy training materials that were provided to you at the trial investigator 
meetings. 
 
13.4 
Quality Control and Quality Assurance 
Novartis maintains a robust Quality Management System that includes all activities involved in 
quality assurance and quality control, to ensure compliance with written Standard Operating 
Procedures as well as applicable global/local GCP regulations and ICH Guidelines. 
Audits of investigator sites, vendors, and Novartis systems are performed by auditors, 
independent from those involved in conducting, monitoring or performing quality control of the 
clinical trial. The clinical audit process uses a knowledge/risk based approach. 
Audits are conducted to assess GCP compliance with global and local regulatory requirements, 
protocols and internal Standard Operating Procedures, and are performed according to written 
Novartis processes. 
 
14 
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 including 


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incidental collection is an investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving any investigational drugs under the protocol, 
other than the purpose of the study. If despite this interdiction prohibition, data, information, 
observation would be incidentally collected, the investigator shall immediately disclose it to 
Novartis and not use it for any purpose other than the study, except for the appropriate 
monitoring on study participants. 
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. 
 
14.1 
Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis/sponsor health authorities where required, and the IRB/IEC prior 
to implementation. 
Only amendments that are required for subject safety 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, Novartis should 
be notified of this action and the IRB/IEC at the study site should be informed according to 
local regulations. 


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15 
References 
References are available upon request 
Blauvelt A, Prinz JC, Gottlieb AB, et al (2014) Secukinumab administration by pre-filled 
syringe: efficacy, safety, and usability results from a randomized controlled trial in psoriasis 
(FEATURE). Br J Dermatol; 28:1127-9. 
Chobanian AV, Bakris GL, Black HR, et al (2003) Seventh report of the joint national 
committee on prevention, detection, evaluation, and treatment of high blood pressure. 
Hypertension; 42: 1206-52. 
Christophers E, Mrowietz U (2003) Psoriasis. In: Freedberg IM, Eisen AZ, Wolff K, et al 
(eds) Fitzpatrick’s Dermatology In General Medicine. 6th ed; New York: McGraw-Hill: 
407-27. 
Committee for medicinal products for human use (CHMP), European Medicines Agency for 
the Evaluation of Medicines for Human Use. (2004) Guideline on clinical investigation of 
medicinal products indicated for the treatment of psoriasis. CHMP/EWP/2454/02 corr 
document. London, UK. 
Doherty SD, Van Voohees A, Lebwohl MG (2008) National psoriasis foundation consensus 
statement on screening for latent tuberculosis infection in patients with psoriasis treated with 
systemic and biologic agents. J Am Acad Dermatol; 59(2): 209-17. 
Finlay AY, Khan GK (1994) Dermatology Life Quality Index (DLQI): A simple practical 
measure for routine clinical use. Clin Exp Dermatol; 19: 210-16. 
Fredriksson T, Pettersson U (1978) Severe psoriasis – oral therapy with a new retinoid. 
Dermatologica; 157: 238-44. 
Gottlieb A, Griffiths CEM, Ho VC, et al (2005) Oral pimecrolimus in the treatment of 
moderate to severe chronic plaque type psoriasis: a double-blind, multicenter, randomized 
dose-finding trial. Br J Dermatol; 152: 1219-27. 
Griffiths CEM, Barker JNWN (2007) Pathogenesis and clinical features of psoriasis. Lancet; 
370: 263-71. 
International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use: ICH Harmonized Tripartite Guideline: Post-approval safety 
data management: definitions and standards for expedited reporting (E2D), November 2003. 
International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use: ICH Harmonized Tripartite Guideline: Guideline for Good 
Clinical Practice (E6R1), June 1996. 
Keininger D, Coteur G (2011) Assessment of self-injection experience in patients with 
rheumatoid arthritis: psychometric validation of the Self-Injection Assessment Questionnaire 
(SIAQ). Health Qual Life Outcomes; 9:2. 
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. 


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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: 861-72. 
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. 
Langley RG, Feldman SR, Nyirady J, et al (2015) The 5-point Investigator’s Global Assessment 
(IGA) Scale: A modified tool for evaluating plaque psoriasis severity in clinical trials, Journal 
of Dermatological Treatment, 26(1): 23-31. 
Leonardi CL, Kimball AB, Papp KA, et al (2008) Efficacy and safety of ustekinumab, a 
human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results 
from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet; 371: 1665- 
74. 
Mancia G, De Backer G, Dominiczak A, et al. (2007) 2007 Guidelines for the Management of 
Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the 
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; 2016. 
Novartis Investigator’s Brochure (2017) Secukinumab, Edition 17. 
Papp KA, Tyring S, Lahfa M, et al (2005) A global phase III 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, Lacour JP, Tedremets L, 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. 


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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. 
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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16 
Appendices 
16.1 
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 Table 8-4. 
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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16.3 
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). 


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2. The transformed scores for items contributing to a domain are then averaged into a 
domain score. 
 
Table 16-3 
Scoring of SIAQ 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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16.4 
Appendix 4: SIAQ Questionnaire 
 
 
Representative examples 
 
 


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SIAQ (Pre-Self-Injection, continued) 
 
 
 
 


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16.5 
Appendix 5: DLQI Questionnaire 
 
 
 


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16.6 
Appendix 6: Determination of Tuberculosis status 
Determination of tuberculosis (TB) status will be required before administration of study 
treatment and should be performed as defined by local guidelines. TB status must be determined 
by medical history, signs, symptoms and TB central lab testing. Any significant findings will 
be recorded in the relevant TB assessment eCRF and the Medical History eCRF, as necessary. 
A central lab testing will be performed to assess the TB status at screening for all subjects. This 
test will only be used to determine subject’s eligibility for the trial. The test will be used to 
screen the subject population for latent tuberculosis infection (Doherty et al 2008). 
This blood-based assay is specific for Mycobacterium tuberculosis and is not influenced by 
previous Bacillus Calmette-Guérin vaccination or 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 tuberculosis 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 16-1. 
a. If the test result is negative, the subject may be randomized. 
b. 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, 
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. 
c. 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. 
i. 
If the second test is negative, the subject may be randomized. 
ii. 
If the second test is positive or indeterminate, the investigator should perform workup 
as per local guidelines. Subject positive for latent TB per workup 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. The subject will not be 


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Clinical Trial Protocol (Version 00) 
Confidential 
Page 90
1 Protocol No. 
 
 
 
eligible for randomization if“active tuberculosis is present”or“latent tuberculosis 
is present” and is untreated per local guidelines. . 
iii. 
Subjects negative for TB per workup (no signs of latent or active TB) may be 
randomized to the trial if the workup 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 Period (within 4 weeks prior to randomization) 
and TB work-up will only be considered if it was completed within 12 weeks prior to 
randomization. 
. 


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Figure 16-1 
Tuberculosis screening flowchart 
 

SAP_001.pdf: 
Clinical Development
AIN457/ Secukinumab/Cosentyx®
CAIN457A2325 / NCT03589885
Multicenter, rAndomized, double-blind, placebo-conTrolled,
52-week stUdy to demonstRatE the efficacy, safety and 
tolerability of subcutaneous secukinumab injections with 2 
mL auto-injectors (300 mg) in adult subjects with moderate 
to severe plaque psoriasis – MATURE
Statistical Analysis Plan (SAP)
Author:
Statistician, 
Document type:
SAP Documentation
Document status:
1.0
Release date:
23 Nov 2018
Number of pages:
57
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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Document History – Changes compared to previous final version of SAP
Date
Time 
point
Reason for 
update
Outcome for 
update
Section and title impacted (Current)
23-Nov-
2018
Prior to 
FPFV
Creation 
of 
final
version
1.0
First version
NA


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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 ...............................................................................9
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 ...................13
2.3.1
Patient disposition.................................................................................14
2.4
Treatments (study treatment, concomitant therapies, compliance) .......................14
2.4.1
Study treatment / compliance................................................................14
2.4.2
Prior, concomitant and post therapies...................................................17
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..........................25
2.7.3
Handling of missing values/censoring/discontinuations.......................25
2.8
Safety analyses.......................................................................................................26
2.8.1
Adverse events (AEs)............................................................................26
2.8.2
Deaths....................................................................................................29
2.8.3
Laboratory data .....................................................................................29
2.8.4
Other safety data ...................................................................................31
.32
33


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2.11
Clinician-reported outcomes..................................................................................33
2.11.1
Usability and hazard assessment of the 2 mL auto-injector..................33
2.12
Patient-reported outcomes .....................................................................................34
2.13
Biomarkers.............................................................................................................35
35
2.15
Interim analysis......................................................................................................35
3
Sample size calculation .....................................................................................................35
3.1
Primary endpoint (co-primary endpoint)...............................................................35
3.1.1
Secondary endpoints .............................................................................35
4
Change to protocol specified analyses ..............................................................................35
5
Appendix ...........................................................................................................................36
5.1
Imputation rules.....................................................................................................36
5.1.1
Study drug.............................................................................................36
5.1.2
AE date imputation ...............................................................................36
5.1.3
Concomitant medication date imputation .............................................37
5.1.4
First diagnosis date (PsO, PsA) imputation ..........................................39
5.1.5
Other imputations..................................................................................39
5.2
AEs coding/grading ...............................................................................................39
5.3
Laboratory parameters derivations ........................................................................40
5.4
Statistical models...................................................................................................40
5.4.1
Analysis of continuous data ..................................................................40
5.4.2
Analysis of binary (and categorical) data..............................................40
5.4.3
Logistic regression ................................................................................41
5.4.4
Multiple imputations for response variables.........................................41
5.4.5
Crude incidence and related risk estimates...........................................45
5.4.6
Exposure adjusted incidence rate and related risk estimates ................46
5.5
Rule of exclusion criteria of analysis sets..............................................................47
5.6
Clinician reported outcomes..................................................................................48
5.6.1
Usability and hazard assessment of the 2 mL auto-injector..................48
5.7
Patient reported outcomes......................................................................................49
5.7.1
Dermatology Life Quality Index (DLQI)..............................................49
5.7.2
Self-injection Assessment Questionnaire (SIAQ).................................51
6
Reference...........................................................................................................................53


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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 12 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 CAIN457A2325 (MATURE) 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 120 subjects with moderate to severe plaque-type psoriasis.
Randomization: Eligible subjects will be randomized using a 2:2:1:1 ratio into one of the 
following 4 treatment arms. In order to achieve a balanced weight distribution in each 
treatment arm, randomization in these four groups will be stratified by body weight at 
baseline (< 90 kg or ≥ 90 kg). Group 1: Secukinumab 300 mg (2 mL AI): one 2 mL 
secukinumab 300 mg AI plus two 1 mL PFS matching placebo secukinumab s.c. injections 
once weekly at Randomization, Weeks 1, 2, and 3, followed by dosing every four weeks, 
starting at Week 4 and until Week 48, except for weeks 13, 14, and 15 where subjects will 
self-administer two 1 mL placebo secukinumab 150 mg PFS plus one 2 mL AI matching 
placebo secukinumab s.c. injections.
Group 2: Secukinumab 300 mg (2 x 1 mL PFS): two 1 mL secukinumab 150 mg PFS plus 
one 2 mL AI matching placebo secukinumab s.c. injections once weekly at Randomization, 
Weeks 1, 2, and 3, followed by dosing every four weeks, starting at Week 4 and until Week 
48, except for weeks 13, 14, and 15 where they will self-administer a weekly dose of the two 
1 mL placebo secukinumab 150 mg PFS plus one 2 mL AI matching placebo secukinumab 
s.c. injections.
Group 3: Placebo - Secukinumab 300 mg (2 mL AI): placebo treatment administered as two 
1 mL placebo secukinumab plus one 2 mL AI matching placebo secukinumab s.c. injections
once weekly at Randomization, Weeks 1, 2, and 3, followed by dosing every four weeks 
starting at week 4 till week 8. Prior to receiving the Week 12 dose, PASI 90 response will be 
evaluated. PASI 90 responders will receive placebo every four weeks from week 12 till week 
48, except for weeks 13, 14, and 15 subjects will self-administer a weekly dose of two 1 mL 
placebo secukinumab 150 mg PFS plus one 2 mL AI matching placebo secukinumab s.c. 
injections. The PASI 90 non-responders will be assigned to Secukinumab 300 mg (2 mL AI) 
group and receive their treatment every four weeks from week 12 till week 48, except for
weeks 13, 14, and 15 where the patients will self-administer a weekly dose of the 
Secukinumab 300 mg (2 mL AI) group treatment.
Group 4: Placebo - Secukinumab 300 mg (2 x 1 mL PFS): placebo treatment administered 
as two 1 mL placebo secukinumab plus one 2 mL AI matching placebo secukinumab s.c. 
injections once weekly at Randomization, Weeks 1, 2, and 3, followed by dosing every four 
weeks till week 8. Prior to receiving the Week 12 dose, PASI 90 response will be evaluated. 
PASI 90 responders will receive placebo every four weeks from week 12 till week 48, except 


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for weeks 13, 14, and 15 subjects will self-administer a weekly dose of two 1 mL placebo 
secukinumab 150 mg PFS plus one 2 mL AI matching placebo secukinumab s.c. injections. 
The PASI 90 non-responders will be assigned to Secukinumab 300 mg (2 mL PFS) group and 
receive their treatment every four weeks from week 12 till week 48, except for weeks 13, 14, 
and 15 where the patients will self-administer a weekly dose of the Secukinumab 300 mg (2 
mL PFS) group treatment.
The following study periods will be considered for analysis:

Screening period (before Randomization) 

Treatment period 1 (Randomization to Week 12 pre-dose)

Treatment period 2 (Week 12 dose to Week 52)

Entire treatment period (Randomization to Week 52, last dose at Week 48)
Of note, no follow-up period is included in this study.
The primary analysis will be provided at the time of Week 16 interim DBL. Treatment period 
up to Week 16 will be presented for the W16 primary analysis and all data will be presented for 
the 
final 
analysis.
The 
study 
design 
is 
presented 
in 
Figure 
3-1.
In the figure, the solid arrow means active drug dosing while the dotted arrow means placebo dosing.


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1.2
Study objectives and endpoints
The primary objective of this study is to demonstrate the efficacy of secukinumab 300 mg 
when administered in 2 mL auto-injector 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.
The key secondary objectives is to demonstrate the efficacy of secukinumab 300 mg when 
administered in 2 mL AI in subjects with plaque-type psoriasis with respect to PASI 90 at week 
12, compared to placebo.
Furthermore, additional aspects of efficacy, safety and tolerability of secukinumab 300 mg 
when administered with a 2 mL auto-injector in subjects with plaque-type psoriasis compared 
to placebo will be investigated. The subject usability and satisfaction with the new secukinumab
2 mL auto-injectors utilizing a self-administered Self-Injection Assessment Questionnaire 
(SIAQ) and investigator/site staff observation of  secukinumab 300 mg 2 mL auto-injector 
administration will be assessed.
This study will provide efficacy and safety data to support a product labeling updates for the 
indication of moderate to severe plaque psoriasis.
Table 1-1
Primary, key secondary, secondary 
Variable
Type
PASI 75 response @ Week 12
primary
IGA 0/1 response @ Week 12
primary
PASI 90 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 (Instructions For Use(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 both Week 16 primary analysis and final analysis. Statistical 
software SAS version 9.4 or later will be used.
Data up to Week 16 will be presented for the Week 16 primary analysis and all data will be 
presented for final analysis.
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.


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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 TLF 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

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, provided as one 2 mL auto-injector (AI)

Control treatment
o
Secukinumab 300 mg, provided as two 1 mL pre-filled syringes (PFS) 
containing 150 mg secukinumab
o
Secukinumab placebo, provided as either one 2 mL AI or two 1 mL PFS


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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 
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. Further information will be found in [Programming Datasets Specifications 
(PDS)].
For efficacy analyses, baseline is the last assessment (including unscheduled visits) obtained 
(on or) before the randomization (day). All assessments obtained after randomization are 
considered as post-baseline unless otherwise specified.
For safety analyses, baseline is the last assessment (including unscheduled visits) obtained (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.
Of note, baseline will be derived based on the randomization day or first dose day, exact 
randomization/dosing time is not considered.
Of note, re-randomization will not be used for baseline definition and only one baseline value 
will be defined referring to the first randomization.
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.
For safety analysis, on-treatment is defined as assessments within last dose plus 84 days.
Of note: study does not have follow up period, the last visit is 4 weeks after last dose.
2.2
Analysis sets
The following analysis sets will be used for the data analysis. 


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Randomized set: The randomized set will be defined as all subjects who were randomized at 
baseline visit. Unless otherwise specified, subjects with missing informed consent form as well 
as 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.
The subjects with severe GCP violation will not be included in the FAS.
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. If a subject has received intermittent wrong treatment, the treatment received will be 
set to the original randomized treatment.
2.2.1
Subgroup of interest
The co-primary endpoints and important secondary endpoints will be evaluated using the 
subgroups defined in Table 2-1. Subgroup analyses for the study endpoints are represented in 
Table 2-2.
Table 2-1
Subgroup definitions
Subgroup 
variables
Categories
Label for outputs
Suffix for 
outputs*
Weight category
body weight category (<90 
kg, >=90 kg)
Weight category
a
* Suffixes will be used for the outputs numbering, see [TFL shell document]
Table 2-2
Subgroup analyses
Endpoint/analysis
Weight category
Co-primary endpoints:
   PASI 75 response @ Week 12
X
   IGA 0/1 response @ Week 12
X
Secondary endpoints:
   PASI 90 response @ Week 12
X
   PASI 50/75/90/100 response over time up to week 52
X
   IGA 0/1 response over time up to week 52
X
Note: presented are only those endpoints that need subgroup analyses.


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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 AI), AIN457 300 mg (2x1mL PFS), Placebo, Total
after Week 12:

AIN457 300 mg (2mL AI), AIN457 300 mg (2x1mL PFS), Placebo, Placebo -
AIN457 300 mg (2mL AI), 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 collected in the RaveX platform directly)
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
o
Weight categories (<90 kg, >= 90 kg)
Psoriasis specific baseline characteristics and history of disease will be summarized as well: 
Continuous variables:
o
Baseline PASI
o
Baseline total BSA
o
Time since diagnosis of psoriasis
o
Time since diagnosis of psoriatic arthritis
Categorical variables:
o
Baseline PASI categories (≤20, >20)
o
Baseline IGA mod 2011 score categories (at least mild, moderate, severe)
o
Severity of psoriasis categories (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))
o
Baseline psoriatic arthritis categories (yes, no)
o
Previous exposure to biologic systemic psoriasis therapy (yes, no)
o
Previous exposure to systemic psoriasis therapy (yes, no)


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o
Previous exposure to non-biologic systemic psoriasis therapy (yes, no)
o
Previous failure to biologic systemic psoriasis therapy (yes, no)
o
Previous failure to systemic psoriasis therapy (yes, no)
o
Previous failure to non-biologic systemic psoriasis therapy (including 
phototherapy and photo- chemotherapy) (yes, no)
Body Mass Index (BMI) will be calculated using the following formula:
BMI = (body weight in kilograms) / (height in meters)2
For BMI, height and body weight 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 5.1.4.
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.


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The number of secukinumab 2mL auto injections, 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”.
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 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 or in the corresponding treatment period.
Duration of exposure (days) = min (“end of study period” 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
The analyses of duration of exposure described above will be done for the treatment period up 
to Week 16 for the primary analysis, with the last category “≥16 weeks”..
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 2-3. 
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 in Section 2.4.1.2.
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.


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Table 2-3
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 
2-4).
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 2-4
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 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 2-5, 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.
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 
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 2-6.
A PASI score (Fredriksson and Pettersson 1978, Weisman et al 2003, Gottlieb et al 2005) will 
be derived as indicated in Table 2-6. 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.


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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 
2-6).
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. PASI and total BSA calculations will be done by investigator at screening 
and randomization only; The PASI scores after randomization 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 2-5
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 2-6) 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 2-6
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 2-7.
Table 2-7
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 50/75/90/100 and IGA 0/1 response 
over time
X
X
X**


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Variable(s)
Summary 
statistics for 
binary/
categorical data 
Logistic 
regression
Summary 
statistics for 
continuous 
data
Time-to-
event 
analysis
Graphs
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 co-primary endpoints of this study are PASI 75 response and IGA mod 2011 0 or 1 response 
at Week 12.
The statistical hypothesis is that secukinumab 300 mg (2 mL AI) 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  denote the proportion of PASI 75 responders at Week 12 for treatment group j and 
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 AI)
The following hypothesis will be tested:

H:  − ≤0 versus :  − > 0,

H:  − ≤0  versus :  − > 0
In other words:
H: Secukinumab 300 mg (2 mL AI) is not superior to placebo with respect to PASI 75
response at Week 12
H: Secukinumab 300 mg (2 mL AI) 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 logistic regression with treatment group (secukinumab 
2mL AI vs Placebo); baseline bodyweight strata and baseline PASI score as explanatory 
variables. Odds ratios will be computed for 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 reponse rates in the placebo group, an exact logistic regression with be 
performed and the detailed analysis is described in Section 4.2.3. In case of response rates of 
0% or of 100% in one of the treatment groups, confidence intervals and p-values from the t-test 
for the risk difference comparing to 0 will be provided for the analyses using multiple 
imputation; for the analyses using non-responder imputation, Fisher’s exact test will be 
performed and confidence intervals for risk difference will be provided.
If logistic regression model does not converge the following steps will be performed:


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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 (baselines PASI score), followed 
by removing categorical covariates (i.e., weight stratum etc.,); 
3. If convergence not reached, perform Fisher’s exact test.
The hypotheses  and  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 AI) has not been 
demonstrated. 
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, the subject will be imputed as 
responder after discontinuation and up to the 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.


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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.
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 endpoint of this study is PASI 90 response at Week 12.
2.6.2
Statistical hypothesis, model, and method of analysis
Testing strategy
As stated in Section 2.5.2, the hypotheses H1 and H2 will be included in co-primary testing 
procedure. Each hypotheses is tested at α = 2.5% (one-sided). The testing sequence will 
continue to key secondary endpoint PASI 90 at α = 2.5% (one-sided) only if both H1 and H2
have been rejected at α (one-sided) such that a family-wise type-I-error of α (one-sided) is kept.
H3: secukinumab 300 mg (2 mL AI) is not superior to placebo with respect to PASI 90 
response at Week 12
PASI 90 response will be analyzed analogously to the primary endpoints at Week 12, i.e., the 
logistic regression model with treatment group, baseline bodyweight strata and baseline PASI 
score as exploratory variables. Odds ratios will be computed for comparisons of secukinumab
versus placebo utilizing the logistic regression model fitted.


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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 exact 
method.
For PASI 50, PASI 75, PASI 90, PASI 100, and IGA mod 2011 0 or 1 response at each visit, 
up to Week 12, comparisons between 2mL AI vs placebo and 2mL AI vs 1mL PFS x 2 will be 
conducted using logistic regression model with treatment group, body weight stratum 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 
will be applied to the treatment group comparisons between 2mL AI versus placebo. In addition, 
the risk difference between 2ml AI group vs. 1ml PFS group, including 95% confidence interval 
(based on normal approximation) may be derived by visit, up to Week 52.
Figures will be provided as well displaying estimates for response rates over time by treatment 
including 95% confidence intervals.
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. Figure will be provided for percentage changes in PASI 
scores over time.
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.
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.


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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. Week 16 primary analysis will include data up to Week 12 for treatment period 1 
and data up to Week 16 last patient last visit (LPLV) for the entire treatment period. 
The following groups will be used for treatment period 1:

AIN457 300 mg (2mL AI): all subjects who are randomized to 300 mg 2mL AI 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 to a placebo group at Randomization visit

Any AIN457 300 mg: Any AIN457 300 mg of (2mL AI) or (2x1mL PFS) as above.
The following groups will be used for entire treatment period:

AIN457 300 mg (2mL AI): all subjects who are randomized to 300 mg 2mL AI 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 AI): all subjects who are randomized to 300 mg 2mL AI
group at Randomization visit and all placebo subjects who are re-assigned to 300 mg 
2mL AI at Week 12, but they are only considered after the treatment re-assignment
(Week 12 treatment injection).

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).

Any AIN457 300 mg: Any AIN457 300 mg of (2mL AI) or (2x1mL PFS) as above.

Placebo: all subjects who are re-assigned will only be considered until the re-
assignment point (Week 12 treatment injection).
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 2-8. 
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)


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All adverse events will be listed with “treatment emergent” flag displayed.
Table 2-8
Overview of analyses on some safety endpoints
Analysis period
AEs & 
SPP/RMP 
risks
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
The crude incidence of treatment emergent adverse events will be presented for the treatment
period up to Week 16 LPLV for W16 primary analysis, and 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 reported separately 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.


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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.
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 
in the Program Case Retrieval Sheet that is stored in 
 
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. 
A separate table of injection site reaction related AEs caused by the 2 mL AI and the 1 mL PFS 
respectively will be provided. Additional analyses on the severity, outcome, etc. of the AEs 
caused by AI and PFS respectively may be performed to support health authority interactions 
as necessary.
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 (PT) with an incidence greater than >2% and on 
SAEs 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


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
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 
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 2-9: 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).


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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 2-9
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 
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 
The number and percentage of subjects with newly occurring liver enzyme abnormalities will 
also be summarized based on the event criteria given in Table 2-10.


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Table 2-10
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.
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.


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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 2-11 below.
A listing of subjects with newly occurring notably abnormal vital signs will be provided.
Table 2-11
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
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 


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2.11
Clinician-reported outcomes
2.11.1
Usability and hazard assessment of the 2 mL auto-injector
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.
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. P7, P9, P10 and P11). 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 auto-injector use rate < 90% 
H1: successful auto-injector 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.


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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. 
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.


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2.13
Biomarkers
Not applicable.
 
 
 
2.15
Interim analysis
Week 16 primary analysis will be performed after all subjects have completed Week 16 visit.
Additional analyses may be performed to support health authority interactions as necessary.
At the End of Study, a final analysis of all data collected up to last study visit (Week 52) will 
be performed when all subjects have completed the last study visit.
Trial modifications are not planned based on any interim analysis.
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 auto-injector s.c.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.
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 40 subjects per group 
and assuming a response rate of 8% 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 auto-injector s.c.) group 
based on Fisher’s exact test (nQuery Advisor 7.01, 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
The study should be sufficiently powered (above 90%) to show a response rate of 46% for
PASI 90 response if the placebo rate is assumed as 8%.
4
Change to protocol specified analyses
The following analyses have been removed:


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
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
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. 


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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). 
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). 


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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). 
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.


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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:
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 DLQIscore, 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 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 


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Program Case Retrieval Sheet that is stored in 
 
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.
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.
p
q

1

,
0
for
0
,0



p
L
p

,
1
for
1
,1



p
U
p


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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 strata 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, Fisher’s exact test will be 
applied. Confidence intervals for risk difference will be derived based on the exact method.
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.
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:
4. Run the PROC GENMOD procedure with EXACT statement; 
5. 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);
6. 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. 


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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 
4572325 for this study. To generate the multiple imputed data sets, the SAS procedure MI can 
be used as follows:
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;


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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 
_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.


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
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;
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;


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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.
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.
p
q

1


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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
)
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):


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Lower confidence limit   
for D>0, 0 otherwise,
Upper confidence limit 
where
k
c ,

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 
(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 ,

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:INCL01, OTH17; 
OTH12
Misrandomized subject
Safety
DVSPID: INCL01, OTH17; 
OTH12
Subjects who did not take any 
study treatment
OTH17: Patient was rescreened, or new/updated ICF available but patient did not sign a new 
ICF
OTH12: Severe ICH-GCP non-compliance of study site
T
c
L
D
2
,
2
/
5.0


T
c
U
D
2
2
,2
/
1
5.0




T
c
L
D
2
,
2
/
5.0


T
c
U
D
2
2
,2
/
1
5.0






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5.6
Clinician reported outcomes
5.6.1
Usability and hazard assessment of the 2 mL auto-injector
The goal is to measure and evaluate the usability of the auto-injector 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 P7, P9, P10 and P11 (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:

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. P7, P9, P10 and P11).
Table 5-2
Self injection assessment checklist (auto-injector)
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 auto-injector from the outer box 
No
P4
Checked expiration date on auto-injector label
No
P5
Inspected the auto-injector for damage
No
P6
Inspected liquid for brown discoloration or particles
No
P7
Removed cap from auto-injector
Yes
P8
Discarded cap
No
P9
Hold the auto-injector at correct angle to the injection site
Yes
P10
Press the auto-injector firmly against the skin to trigger the injection 
(1st Click), and keep holding the auto-injector firmly against the skin
Yes
P11
Wait until the injection is complete, confirmed by the 2nd “click” 
and/or a check that the yellow indicator fills the window
Yes


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No.
IFU indicated steps
Required to be 
completed for 
successful 
administration
P12
The auto-injector can now be removed
No
P13
Check again that the yellow indicator fills the window
No
P14
Disposed used auto-injector 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?
H8
Was any other problem observed?3
H9
Was less than the full dose administered?4
The following potential hazards from the Hazards Identified List ([AIN457_HID_Delta225-01]) have not 
been included as not being observable during self-injection observation: microbiological contamination, 
wrong drug, transfer of transmissible diseases.
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 DLQI in this trial.
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


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
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
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:


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
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.
5.7.2
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 2 mL AI and before the 1 mL PFS 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 5-4).
Table 5-4
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


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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 plunger or button on 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?
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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6
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