Clinical trial NCT02595970
Conditions: Psoriasis
Keywords: Psoriasis Secukinumab Simplified Psoriasis Index CAIN457A AIN457AFR01 AIN457A Skin condition skin disease itching condition psoriasis vulgaris relapsing/remitting psoriasis immune-mediated systemic disease skin lesions red skin lesions scaly patches papules plaques itching
Sponsor: Novartis Pharmaceuticals
Start date: 2015-05-20; Completion date: 2017-02-09
Enrollment: 120 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Evaluate psoriasis severity and its psychosocial impact using a novel Patient Reported Outcome (the Simplified Psoriasis Index SPI) at 16 weeks, as well as long-term safety, tolerability and efficacy of secukinumab administered subcutaneously during 52 weeks (plus extension) in patients with moderate to severe psoriasis.

Detailed description:
Study to Evaluate Psoriasis Severity and Its Psychosocial Impact Using the Simplified Psoriasis Index (SPI), as Well as Long-term Safety, Tolerability and Efficacy of Secukinumab Administered Subcutaneously in Patients With Moderate to Severe Psoriasis

Arms: arm 1: Weekly sub cutaneous injections of 300 mg during the first month and then Monthly until Week 52 plus extension until 03/11/2016.
Interventions: intervention 1: Secukinumab
Intervention descriptions: intervention 1: weekly sub cutaneous injections of 300 mg during the first month and then monthly until week 52 plus extension until 03/11/2016.

Protocol documents:
Prot_000.pdf: 
 
 
 
Clinical Development 
Secukinumab, AIN457 
 
Clinical Trial Protocol CAIN457AFR01 / NCT02595970 
A 52-week (plus extension until commercialization), single-
arm study to evaluate psoriasis severity and its 
psychosocial impact using the Simplified Psoriasis Index 
at 16 weeks, as well as long-term safety, tolerability and 
efficacy of secukinumab administered subcutaneously in 
patients suffering from moderate to severe psoriasis.  
Authors: 
 
Document type: 
Amended Clinical Trial Protocol  
EUDRACT number: 
2014-003666-25 
Version number: 
Version 05 (Protocol amendment 5) 
Development phase: 
Phase IIIb 
 
Release date: 
22-Mar-2016  
      Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed  
without the consent of Novartis 
NCDS Template Version 03-Feb-2012 


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Table of contents 
Table of contents ................................................................................................................. 5 
List of tables ........................................................................................................................ 8 
List of figures ...................................................................................................................... 8 
List of abbreviations ............................................................................................................ 9 
Glossary of terms ............................................................................................................... 12 
Amendment 1 .................................................................................................................... 13 
Amendment 2 .................................................................................................................... 14 
Amendment 3 .................................................................................................................... 15 
Amendment 4 .................................................................................................................... 16 
Amendment 5 .................................................................................................................... 18 
1 
Introduction ....................................................................................................................... 31 
2 
Study objectives ................................................................................................................. 32 
2.1 
Primary and key secondary objectives .................................................................. 32 
2.1.1 
Primary objective .................................................................................. 32 
2.1.2 
Key secondary objectives ...................................................................... 32 
2.2 
Secondary objectives ............................................................................................. 32 
2.3 
Exploratory objectives ........................................................................................... 32 
3 
Investigational plan ........................................................................................................... 33 
3.1 
Study design........................................................................................................... 33 
3.1.1 
Screening period .................................................................................... 35 
3.1.2 
Treatment period ................................................................................... 35 
3.1.3 
Extension period.................................................................................... 35 
3.1.4 
Follow-up period ................................................................................... 36 
3.2 
Rationale of study design ....................................................................................... 36 
3.3 
Rationale of dose/regimen, route of administration and duration of treatment ..... 36 
3.4 
Rationale for choice of comparator ....................................................................... 36 
3.5 
Purpose and timing of interim analyses/design adaptations .................................. 36 
3.6 
Risks and benefits .................................................................................................. 37 
4 
Population .......................................................................................................................... 38 
4.1 
Inclusion criteria .................................................................................................... 38 
4.2 
Exclusion criteria ................................................................................................... 39 
5 
Treatment ........................................................................................................................... 41 
5.1 
Protocol requested treatment ................................................................................. 41 
5.1.1 
Investigational drug ............................................................................... 41 
5.1.2 
Additional study treatment .................................................................... 41 


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5.2 
Treatment arms ...................................................................................................... 41 
5.3 
Treatment assignment, randomization ................................................................... 41 
5.4 
Treatment blinding ................................................................................................. 42 
5.5 
Treating the patient ................................................................................................ 42 
5.5.1 
Patient numbering ................................................................................. 42 
5.5.2 
Dispensing the investigational treatment .............................................. 42 
5.5.3 
Handling of study drug.......................................................................... 42 
5.5.4 
Instructions for prescribing and taking investigational drug................. 43 
5.5.5 
Extension period.................................................................................... 44 
5.5.6 
Permitted dose adjustments and interruptions of investigational 
drug ....................................................................................................... 44 
5.5.7 
Rescue medication ................................................................................ 44 
5.5.8 
Prior and concomitant treatment ........................................................... 44 
5.5.9 
Prohibited Treatment ............................................................................. 45 
5.5.10 
Discontinuation of investigational drug and premature patient 
withdrawal ............................................................................................. 47 
5.5.11 
Emergency breaking of treatment assignment ...................................... 48 
5.5.12 
Study completion and post-study treatment .......................................... 48 
5.5.13 
Early study termination ......................................................................... 48 
6 
Visit schedule and assessments ......................................................................................... 48 
6.1 
Information to be collected on screening failures.................................................. 49 
6.2 
Patient demographics/other Screening characteristics ........................................... 54 
6.3 
Baseline characteristics, questionnaires and scores ............................................... 56 
6.4 
Treatment exposure and compliance ..................................................................... 56 
6.5 
Efficacy .................................................................................................................. 56 
6.5.1 
Psoriasis questionnaires and scores ....................................................... 56 
6.5.2 
DLQI questionnaire ............................................................................... 59 
6.5.3 
Appropriateness of efficacy assessments .............................................. 60 
6.6 
Safety ..................................................................................................................... 60 
6.6.1 
Physical examination ............................................................................ 60 
6.6.2 
Vital signs.............................................................................................. 60 
6.6.3 
Height and weight ................................................................................. 61 
6.6.4 
Laboratory evaluations .......................................................................... 61 
6.6.5 
Pregnancy and assessments of fertility ................................................. 61 
6.6.6 
Appropriateness of safety measurements .............................................. 61 
6.7 
Other assessments .................................................................................................. 62 
6.7.1 
Sexual function...................................................................................... 62 


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7 
Safety monitoring .............................................................................................................. 62 
7.1 
Adverse events ....................................................................................................... 62 
7.2 
Serious Adverse Events ......................................................................................... 63 
7.3 
Serious Adverse Event reporting ........................................................................... 64 
7.3.1 
Notification of an SAE to Novartis Pharmaceuticals Drug Safety & 
Epidemiology (DS&E) Department ...................................................... 64 
7.3.2 
Reporting procedure for an SAE ........................................................... 65 
7.4 
Pregnancy reporting ............................................................................................... 65 
8 
Data review and database management ............................................................................. 66 
8.1 
Site monitoring ...................................................................................................... 66 
8.2 
Data collection ....................................................................................................... 66 
8.3 
Database management and quality control ............................................................ 66 
8.4 
Data Monitoring Committee .................................................................................. 67 
8.5 
Adjudication Committee ........................................................................................ 67 
9 
Data analysis ...................................................................................................................... 67 
9.1 
Analysis sets .......................................................................................................... 68 
9.2 
Patient demographics and other Baseline characteristics ...................................... 68 
9.3 
Medical history ...................................................................................................... 68 
9.4 
Treatments ............................................................................................................. 68 
9.4.1 
Investigational drug ............................................................................... 68 
9.4.2 
Prior and concomitant treatment ........................................................... 68 
9.5 
Analysis of the primary and key secondary variable(s)......................................... 69 
9.5.1 
Variable(s) ............................................................................................. 69 
9.5.2 
Statistical model, hypothesis, and method of analysis .......................... 69 
9.5.3 
Handling of missing values/censoring/discontinuations ....................... 70 
9.5.4 
Supportive analyses ............................................................................... 70 
9.6 
Analysis of secondary variables ............................................................................ 70 
9.6.1 
Efficacy variables .................................................................................. 70 
9.6.2 
Safety variables ..................................................................................... 71 
9.6.3 
Resource utilization ............................................................................... 72 
9.6.4 
Health-related Quality of Life ............................................................... 72 
9.6.5 
Pharmacokinetics .................................................................................. 72 
9.6.6 
Pharmacogenetics/pharmacogenomics ................................................. 72 
9.6.7 
Biomarkers ............................................................................................ 72 
9.6.8 
PK/PD ................................................................................................... 72 
9.7 
Exploratory analyses .............................................................................................. 72 


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9.8 
Interim analyses ..................................................................................................... 73 
9.9 
Sample size calculation .......................................................................................... 73 
10 Ethical considerations ........................................................................................................ 73 
10.1 
Regulatory and ethical compliance ........................................................................ 73 
10.2 
Informed consent procedures ................................................................................. 73 
10.3 
Responsibilities of the investigator and IRB/IEC .................................................. 74 
10.4 
Publication of study protocol and results............................................................... 74 
11 Protocol adherence ............................................................................................................ 74 
11.1 
Protocol amendments ............................................................................................. 75 
12 References ......................................................................................................................... 75 
13 Appendices ........................................................................................................................ 77 
13.1 
Appendix 1: SPI questionnaire .............................................................................. 77 
13.2 
Appendix 2 : PASI score ....................................................................................... 83 
13.3 
Appendix 3: SA-PASI score .................................................................................. 84 
13.4 
Appendix 4 : DLQI questionnaire ......................................................................... 85 
13.5 
Appendix 5 : Pain, itching and scaling assessment ............................................... 86 
13.6 
Appendix 6 : BISF-M ............................................................................................ 87 
13.7 
Appendix 7 : BISF-W ............................................................................................ 92 
13.8 
Appendix 8: Normal ranges of values for vital signs ............................................ 96 
13.9 
Appendix 9: Clinically notable laboratory findings .............................................. 96 
 
List of tables 
Table 5-1 
Prohibited treatment .............................................................................. 46 
Table 6-1 
Assessment schedule ............................................................................. 50 
Table 6-2 
Assessment schedule during extension treatment period only .............. 53 
 
List of figures 
Figure 3-1 
Study design .......................................................................................... 34 
 


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List of abbreviations 
AE 
Adverse Event 
ALT (SGPT) 
Alanine aminotransferase 
ANCOVA 
Analysis of Covariance 
AST (SGOT) 
Aspartate aminotransferase 
ATC 
Anatomic Therapeutic Chemical  
BISF-m/w 
Brief Index of Sexual Functioning (man or woman) 
BL 
Baseline 
BSA 
Body Surface Area 
CI 
Confidence Interval 
CRO 
Contract Research Organization 
CS 
CorticoSteroids 
CsA 
Cyclosporine A 
CT 
Computed Tomography 
DLQI 
Dermatology Life Quality Index 
DS&E 
Drug Safety and Epidemiology 
ECG 
ElectroCardioGram 
eCRF 
electronic Case Report/Record Form  
EDC 
Electronic Data Capture 
EMA 
European Medicines Agency 
EOE 
End of Extension 
EOT 
End of Treatment 
FAS 
Full Analysis Set 
FU 
Follow-Up 
GCP 
Good Clinical Practice 
GGT 
Gamma Glutamyl Transpeptidase 
hCG 
Human Chorionic Gonadotropin 
HDL 
High Density Lipoprotein 
HIV 
Human Immunodeficiency Virus 
i 
Intervention 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization of  Technical Requirements 
for Registration of Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IGA 
Investigator’s Global Assessment 
IL 
Interleukin 
i.m. 
Intramuscular 
IN 
Investigator Notification 


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IRB  
Institutional Review Board 
IS 
Included Set 
IUD 
IntraUterine Device 
IUS 
IntraUterine System 
i.v. 
Intravenous 
LDL 
Low Density Lipoprotein 
LLN 
Lower Limit of Normal 
LOCF 
Last Observation Carried Forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic Resonance Imaging 
p 
Psychosocial 
PASI 
Psoriasis Area and Severity Index 
PFS 
Pre-Filled Syringes 
PPS 
Per Protocol Set 
Pro 
Professional 
PRO 
Patient-Reported Outcome 
PsA 
Psoriatic Arthritis 
PT 
Preferred Term 
PUVA 
Psoralen + UVA therapy 
QFT 
QuantiFERON TB-Gold test 
RBC 
Red Blood Cell 
REB 
Research Ethics Board 
s 
Severity 
s.c. 
Subcutaneous 
sa 
Self-assessed 
SA 
Self-Administered 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAF 
Safety Analysis Set 
SD 
Standard Deviation 
SGA 
Subject’s Global Assessment 
SOC 
System Organ Class 
SPI 
Simplified Psoriasis Index 
TB 
Tuberculosis 
TCS 
Topical CorticoSteroids 
TEAE 
Treatment-Emergent Adverse Event 
TNF 
Tumor Necrosis Factor 
ULN 
Upper Limit of Normal 


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UV 
UltraViolet 
VAS 
Visual Analog Scale 
W 
Week 
WBC 
White Blood Cell 
WHO 
World Health Organization 


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Glossary of terms 
 
Assessment 
A procedure used to generate data required by the study 
Baseline 
Time point before attribution of study treatment (Visit 1)  
All Baseline assessments should be performed at the latest immediately 
prior to the first study treatment administration i.e. at Visit 0 and Visit 1 
Enrollment 
Point/time of patient entry into the study; the point at which informed 
consent must be obtained (i.e. prior to starting any of the procedures 
described in the protocol) 
Investigational drug 
The drug whose properties are being tested in the study; this definition is 
consistent with US CFR 21 Section 312.3 and is synonymous with 
“investigational new drug” or “investigational medicinal product.” 
Patient number  
A number assigned to each patient who enrolls into the study  
Period 
 
The planned stage of the patients’ participation in the study. Each period 
serves a purpose in the study as a whole. Typical periods are: 
determination of patient eligibility, wash-out of previous treatments, 
exposure of patient to treatment or to follow-up of patients after treatment 
has ended. 
Premature patient withdrawal 
Point/time when the patient exits from the study prior to the planned 
completion of all investigational/study drug administration and all 
assessments (including follow-up) 
Investigational drug 
discontinuation 
Point/time when patient permanently stops taking investigational drug  for 
any reason; may or may not also be the point/time of premature patient 
withdrawal 
Variable 
Information used in the data analysis; derived directly or indirectly from 
data collected using specified assessments at specified time points 
 


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Amendment 1 
 
Amendment rationale : 
 
The purpose of this amendment is to modify the inclusion criteria N°3 :  
 
“ Patients eligible for treatment with a biotherapy i.e. not adequately controlled with at least 
two conventional systemic therapies (including methotrexate, cyclosporine, phototherapy). “  
To 
“ Patients candidates for systemic therapy. “  
This modification is in line with the positive opinion published on November 2014 by the 
Committee 
for 
Medicinal 
Products 
for 
Human 
Use 
(CHMP) opinion. 
Cosentyx (secukinumab) was recommended by the CHMP as new treatment option for 
psoriasis with the following indication :  
“Cosentyx® (Secukinumab, INN) is indicated for the treatment of moderate to severe plaque 
psoriasis in adults who are candidates for systemic therapy.” 
 
Changes to the protocol are related to the following sections:  
- 
Section 1 Introduction 
- 
Section 3.6 Risks and benefits 
- 
Section 4 Population 
- 
Section 4.1 Inclusion criteria 
 


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Amendment 2 
 
Amendment rationale : 
 
The purpose of this amendment is to modify the inclusion criterion N° 14 and add one  
exclusion criterion and one precaution for use :  
 
N° 14 : “Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using highly effective methods of contraception during 
dosing of study treatment and for 16 weeks after stopping treatment.” 
To 
N° 14 : “Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using highly effective methods of contraception during 
dosing of study treatment and for 20 weeks after stopping treatment.” 
 
N° 20 : Patients with a history of hypersensitivity to latex. 
 
The following precaution for use is added after the list of exclusion criteria :  
“Caution should be exercised when prescribing Cosentyx® to patients with Crohn’s disease as 
exacerbations of Crohn’s disease, in some cases serious, were observed in clinical studies in 
both Cosentyx® and placebo groups. Patients who are treated with Cosentyx® and have 
Crohn’s disease should be followed closely.” 
The changes are in line with the Summary of Product Characteristics and the Health Authority 
(ANSM) requests.  
 
Changes to the protocol are related to the following section:  
- 
Section 4.2 Exclusion criteria 


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Amendment 3 
 
Amendment rationale : 
 
The purpose of this amendment is to use the Cosentyx Summary of Product Characteristics as 
reference document to assess whether reported adverse events are of expected or unexpected 
nature. 


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Amendment 4 
 
Amendment rationale : 
The purpose of this amendment is to bring clarifications to the study population, to define 
baseline, to update instructions for administration of questionnaires, to correct inconsistencies 
about X-ray assessment as well as other minor inconsistencies, and to add details on PASI, 
BSA and IGAmod2011 assessments. The reason for these changes is feedback from the first 
initiated study sites. 
List of changes and reasons are given below: 
• to clarify the inclusion criteria 2: ‘Patient with a history of chronic M/S psoriasis …’ 
Protocol requests that patient have moderate to severe psoriasis for at least 6 months. 
It is not requested that patients have documented PASI and IGA scores 6 months 
before inclusion. These scores are assessed at inclusion. 
• to add exclusion criteria 21: ’Form of psoriasis other than plaque … ’ 
As the SPI contains question on erythrodemic and pustular psoriasis (this 
questionnaire is intended for all forms of psoriasis), it might be understood that such 
patients could be included. In line with non inclusion criterion n° 5 ‘Patient with skin 
condition other than M/S plaque psoriasis that may confound psoriasis evolution … ’, 
a specific non inclusion criterion is added. 
• to define the Baseline visit in The Glossary of terms table. 
No formal definition was given in previous version of the protocol. 
• to clarify assessments described in Table 6-1 and Section 6.2 at screening visit: 
- 
to delete reference to the Educational prospect at Baseline (there was a confusion 
between the question on education level at V0 and the optional Education prospect 
questionnaire) 
- 
to correct the delay for X-ray (from 6 months to 12 weeks) in accordance with 
exclusion criteria n° 17 (now § 6.2.1.3). 
- 
to add a formal description of IGAmod2011 and BSA (now § 6.2.1.4&5). 
- 
 In Table 6.1: 
o to add assessment of PASI score at V0, in line with amended inclusion 
criterion # 1. 
o to correct ‘Optional Education level’ to ‘Education level’(same confusion as 
cited above). 
o to add foot note on home administration of study drug (to be consistent to § 
5.5.4.1). 
• to add Baseline definition and time of completion of scores in § 6.3.   
• to add instructions for the order of psoriasis questionnaires and scores (now § 6.5.1). 


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• PASI scores section was updated to provide the full table of detailed measurements for 
the PASI score (now § 6.5.1.2). 
• to clarify the PRO questionnaire completion in § 8.3 (Questionnaires will not be 
completed at home). 
• to update the PASI and SAPasi scores detailed in Appendix. 
Changes in the Informed consent form 
• to correct the table of evaluations in the Informed consent form:  
o deletion of the questionnaire on the impact of psoriasis on education prospects 
and work limitations at V0 (same confusion as cited above); 
o addition of PASI evaluation at V0 (to be consistent with amended inclusion 
criterion 1). 


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Amendment 5 
 
Amendment description and rationale : 
 
The purposes of this amendment and reasons for changes are: 
• to add an extension treatment period until 3 January 2017 or until commercialization 
of Cosentyx in France, whichever occurs first. The aim of this extension is to prevent 
any interruption of  Cosentyx treatment for patients who are deemed to be benefiting 
from the study drug and to collect further safety data. 
Because current LPLV is planned on 3 January 2017, this extension treatment period 
will not increase the overall treatment period of this study. 
• to delete the optional assessment related to the education prospects and work 
limitations questionnaire (DANIELE) 
 
 
• to specify the optional nature of band neutrophils (an intermediary step prior to the 
complete maturation of segmented neutrophils) in hematology evaluations, to do this 
assessment in optional. This is related to the feedback from the first patients’ data 
showing that this tests was unfrequently performed; 
• to correct inconsistencies about the record of AEs occurring after signature of 
informed consent form and before starting investigational treatment on Case Report 
Form, due to the feedback of such initiated study sites; 
• to update the method of analysis of primary objectives and secondary variables 
because the more appropriate statistical analysis for an one armed trial is a paired t-
test;  
• to specify the sample size calculation based on an analysis of paired differences; 
• and other minor inconsistencies for clarify (1) the amendment 4 rational, (2) the use of 
regimen of topical corticosteroids and the record of procedures, (3) significant non-
drug therapies recorded on CRFs due to the feedback of such initiated study sites. 
 
These changes to the protocol are related to the following sections: 
• About the extension treatment period 
- Section 2.2 Secondary objectives 
- Section 3.1 Study design 
- Section 3.2 Rationale of study design 
- Section 4.1 Inclusion criteria 


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- Section 5.5.5 Extension period 
- Section 6 Visit schedule and assessments 
- Section 9 Data analysis 
• About the Daniele questionnaire: 
- Section 2.3 Exploratory objectives 
- Section 6.5.1 Psoriasis questionnaires and scores 
- Section 6.7.2 Education prospects and work limitations 
- Section 8.3 Database management and quality control 
- Section 9.7 Exploratory analyses 
- Appendix 8 Education prospects and work limitation 
- Section 12 References 
• About the optional nature of band neutrophils: 
- Table 6-1 Assessment schedule 
- Section 6.6.4 Laboratory evaluations 
• About the record of AEs on CRFs: 
- Section 7.1 Adverse events 
• About the methods of statistical analysis: 
- Section 9.1 Analysis sets 
- Section 9.4 Treatments 
- Section 9.5 Analysis of the primary and key secondary variable(s) 
- Section 9.6 Efficacy variables 
• About the Sample size calculation: 
- Section 9.9 Sample size calculation 
• About the other minor inconsistencies: 
- Section 5.5.7 Prior and concomitant treatment 
- Section 5.5.8 Prohibited Treatment (Table 5-1 Prohibited Treatment) 
- Section 12 References 


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Protocol synopsis 
  
Protocol number 
CAIN457AFR01 
Title 
A 52-week (plus extension until commercialization) single-arm 
study to evaluate psoriasis severity and its psychosocial impact 
using the Simplified Psoriasis Index at 16 weeks, as well as long-
term safety, tolerability and efficacy of secukinumab administered 
subcutaneously in patients suffering from moderate to severe 
psoriasis 
Brief title 
 
Study of the severity and psychosocial impact on patients suffering 
from moderate to severe psoriasis treated by secukinumab 
Sponsor and Clinical 
Phase 
Novartis, Phase IIIb  
Investigation type 
Drug 
Study type 
Interventional  
Purpose and rationale 
Chronic plaque psoriasis is a common inflammatory dermatosis that 
can have a profound impact on a patient’s life as it can cause major 
distress since it impacts on physical and psychological functioning.  
A new tool has been developed (Simplified Psoriasis Index: SPI), to 
provide a concise but holistic summary of psoriasis assessment. It 
has several advantages over current tools: 1) it evaluates specifically 
several critical localizations (scalp, face, hands, feet, anogenital 
skin); 2) it is assessed by both the physician (proSPI component) 
and the patient (saSPI); and 3) it assesses psychological impact and 
includes historical features. 
This single-arm study is designed to evaluate the psoriasis severity 
and its psychosocial impact using the SPI at 16 weeks in patients 
suffering from moderate to severe psoriasis and treated by 
secukinumab. This index comprises 3 components: severity (s), 
psychosocial (p) and intervention, (i) evaluated by both the 
physician (proSPI) and the patient (self-assessed: saSPI).  
This study will assess the changes from Baseline of the severity (s) 
component of SPI evaluated by both the physician (proSPI (s)) and 
the patient (saSPI (s)). 
In order to collect efficacy and safety data related to the long-term 
administration of secukinumab, patients will be followed up to 
56 weeks. 
Primary Objective(s) 
and Key Secondary 
Objective 
Primary objective: 
To evaluate the benefit of secukinumab on the severity of psoriasis 


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based on the SPI (Simplified Psoriasis Index). This index comprises 
3 components: severity (s), psychosocial (p) and intervention (i) 
evaluated by both the physician (proSPI) and the patient 
(self-assessed: saSPI).  
Only the severity (s) component will be evaluated for the primary 
objective (both proSPI (s) and saSPI (s)). Changes at Week 16 
compared to Baseline in patients suffering from moderate to severe 
plaque psoriasis will be analyzed. 
Key secondary objectives: 
• To assess PASI (weekly from week 0 to 4 then every 4 to 8 
weeks until Week 56). 
• To evaluate correlation between PASI and proSPI (s).  
Secondary Objectives 
 
• To assess each component of proSPI (s, p and i) over time 
(weekly from Week 0 to 4 then every 4 to 8 weeks until Week 
56). 
• To assess each component of saSPI (s, p and i) over time 
(weekly from Week 0 to 4 then every 4 to 8 weeks until Week 
56). 
• To assess DLQI over time (weekly from Week 0 to 4 then every 
4 to 8 weeks until Week 56). 
• To assess self-administered PASI (SA-PASI) (weekly from 
Week 0 to 4 then every 4 to 8 weeks until Week 56).  
• To assess pain, itching and scaling using the Psoriasis Symptom 
Diary questionnaire over time (weekly from Week 0 to 4 then 
every 4 to 8 weeks until Week 56). 
• To evaluate correlation between proSPI (for each component: s, 
p and i) and DLQI. 
• To evaluate correlation between proSPI (for components p and 
i) and PASI. 
• To evaluate safety during the treatment period (until the W52) 
and during the extension period (after the W52) 
Exploratory Objectives 
 
• To evaluate correlation between saSPI (for each component: s, p 
and i) and DLQI.  
• To evaluate correlation between proSPI and saSPI for 
component s and p. 
• To evaluate correlation between saSPI (s) and PASI.  
• To evaluate the ability of SPI to discriminate between 
responders and non-responders based on PASI response. 
• To explore sexual dysfunction using the Brief Index of Sexual 
Functioning (BISF-m or BISF-w) questionnaire (in a subset of 
subjects willing to complete sexual function questionnaire).  


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Study design 
This is an open-label multicenter, single arm study in approximately 
120 patients with moderate to severe psoriasis in approximately 
20 centers in France. The study consists of three periods (Screening, 
Treatment and Follow-up) with a total of 15 visits and 16 injections 
with investigational drug. Eligible patients who have received their 
injection of study drug at W48 before Cosentyx® is marketed in 
France will enter the extension period to receive secukinumab until 
commercialization of Cosentyx® in France.  
Patients who have received their last injection (W48) after 
secukinumab is marketed in France will complete the study as 
initially planned (EOT visit at W52 and Follow-up visit at W56). 
An initial one-month (maximum) screening period after screening 
visit allows wash-out of prohibited medications prior to starting the 
study. Eligible patients are scheduled to receive weekly injections of 
investigational drug during the first month (induction period), 
followed by monthly injections thereafter to Week 16. The primary 
objective will be assessed at 16 weeks prior to injection of 
investigational drug at this visit. If the investigational drug is judged 
by the investigator and patient to be beneficial to the patient, the 
response to treatment will be considered to be favorable and 
monthly injections will continue to Week 48. In the absence of a 
favorable response at Week 16, the investigational drug will be 
discontinued and the patient should attend End of Treatment visit 
and will then enter the follow-up period (after EOT visit, the 
investigator will discuss with the patient the best treatment options). 
Treatment should last a maximum of 12 months, except for patients 
receiving their W48 injection of study drug before secukinumab is 
marketed in France. Patient receiving their W48 injection of study 
drug before secukinumab is marketed in France will enter an 
extension period until 3 January 2017 (LPLV) or until 
commercialization of secukinumab in France, whichever occurs 
first. Patients will be monitored over a further eight weeks after the 
last injection of investigational drug. LPLV will be no later than 3 
January 2017, therefore the last possible administration of 
secukinumab during the study can be 3 November 2016 at the latest, 
whether Cosentyx® is commercialized or not. 
Population 
The study population will consist of adult male and female 
out-patients (≥ 18 years old) with a history of moderate to severe 
plaque psoriasis for at least 6 months before the screening visit and 
who are candidates for systemic therapy. Patient may either have 
received previous biotherapy or be biological naïve. At screening 
visit, patients need to have the following scores: PASI ≥ 12; Body 
Surface Area: BSA ≥ 10 and Investigator Global Assessment: IGA 
mod 2011 ≥ 3. At baseline visit, patients need to have a PASI score 
≥ 12. 


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It is planned to include a total of approximately 100 patients in 
around 20 centers. Anticipating a drop-out of 20 patients, 
approximately 120 patients will need to be screened. 
Inclusion criteria 
• Patients aged ≥ 18 years old at the Screening visit. Patients 
with a history of chronic moderate to severe plaque psoriasis 
for at least 6 months before the Screening visit. Furthermore, 
patients need to have the following scores:  
• PASI ≥ 12, BSA ≥ 10 and IGA mod 2011 ≥ 3 at 
Screening visit and  
• PASI ≥ 12 at Baseline visit 
• Patients candidates for systemic therapy 
• Patients able to understand and communicate with the 
investigator and comply with the requirements of the study 
(including administration of s.c. injections at home), capable 
of and willing to complete several questionnaires at visits, 
and must provide written, signed and dated informed consent 
before any study related activity is performed. 
• For the extension treatment period (Patient who receiving 
their injection of study drug at W48 before Cosentyx® is 
marketed in France): favorable clinical benefit of study 
treatment as judged by the investigator and patient. Patient 
willing to continue receiving secukinumab. 
Exclusion criteria 
1. Patients with a history of hypersensitivity to the study drug 
or to drugs of a similar chemical class. 
2. Patients with recent (previous 6 weeks) or planned 
vaccination with live virus. 
3. Patient participation in another clinical study during the 4 
weeks prior to study drug initiation or 5 half-lives 
(whichever is the longest). 
4. Patients taking other drugs for psoriasis (e.g. corticosteroids, 
vitamin D analogs, pimecrolimus, retinoids, salicylvaseline, 
salicylic acid, lactic acid, tacrolimus, tar, urea, α-hydroxy or 
fruit acids). 
5. Patients suffering from a skin condition other than moderate 
to severe plaque psoriasis that may confound psoriasis 
evaluation, or other inflammatory disease. 
6. Patients suffering from drug-induced psoriasis (e.g. new 
onset or current exacerbation by beta-blockers, calcium 
channel inhibitors, or lithium), as judged by investigator. 
7. Patients with underlying condition(s) (including, but not 
limited to metabolic, hematologic, renal, hepatic, pulmonary, 
neurologic, endocrine, cardiovascular (eg: heart failure 
NYHA class III or IV, unstable angina….), infectious,  


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gastrointestinal or psychiatric) which in the opinion of the 
investigator significantly immunocompromises the patient 
and/or places the patient at unacceptable risk for receiving an 
immunomodulatory therapy). 
8. Patients with previous treatment with any agent targeting 
Interleukin (IL)-17 directly or IL-17 receptor (e.g. 
secukinumab, ixekizumab, or brodalumab).  
9. Patients refusing to limit sunlight or Ultraviolet (UV) light 
exposure. 
10. Patients unwilling to be subjected to repeated s.c. injections 
and venipuncture.  
11. History of an ongoing, chronic or recurrent infectious 
disease, or evidence of tuberculosis (TB) infection as defined 
by a positive or indeterminate QuantiFERON TB-Gold test 
(QFT) at screening visit. Patients with a positive QFT test 
may participate in the study if a full tuberculosis work up 
(according to local practice/guidelines) completed at least 
12 weeks prior to study drug initiation establishes 
conclusively that the patient has no evidence of active 
tuberculosis. If the presence of latent tuberculosis is 
established, then treatment must have been initiated and 
maintained according to guidelines for at least 4 weeks prior 
to study drug initiation. 
12. History of lymphoproliferative disease or any known 
malignancy or history of malignancy of any organ system 
within the past 5 years (except for skin Bowen’s disease, or 
basal cell carcinoma or actinic keratoses that have been 
treated with no evidence of recurrence in the past 12 weeks; 
carcinoma in situ of the cervix or non-invasive malignant 
colon polyps that have been removed). 
13. 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). 
14. Women of child-bearing potential, defined as all women 
physiologically capable of becoming pregnant, unless they 
are using highly effective methods of contraception during 
dosing of study treatment and for 20 weeks after stopping 
treatment. Highly effective contraception methods include: 
• Total abstinence: when this is in line with the preferred 
and usual lifestyle of the subject. Periodic abstinence 
(e.g. calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of 
contraception. 


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• Female 
sterilization: 
have 
had 
surgical 
bilateral 
oophorectomy (with or without hysterectomy) or tubal 
ligation at least 6 weeks before taking study treatment. In 
case of oophorectomy alone, only when the reproductive 
status of the woman has been confirmed by follow up 
hormone level assessment. 
• Male 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. 
• Combination of any two of the following methods (a+b 
or a+c or b+c): 
 
a. Use of oral, injected or implanted hormonal methods 
of contraception or other forms or hormonal 
contraception that have complete efficacy (failure <1%), 
e.g. hormone vaginal ring or transdermal hormone 
contraception. 
 
b. Placement of an intrauterine device (IUD) or 
intrauterine system (IUS). 
 
c. Barrier methods of contraception: condom or occlusive 
cap (diaphragm or cervical/vault caps) with spermicidal 
foam/gel/film/cream/vaginal suppository.  
 
In case of use of oral contraception, women should have 
been stable on the same pill for a minimum of 12 weeks 
before taking study treatment.  
 
NOTE: Women are considered post-menopausal and not 
of child-bearing potential if they have had:  
• 12 months of natural (spontaneous) amenorrhea with an 
appropriate clinical profile (e.g. age appropriate, history 
of vasomotor symptoms). 
• Surgical bilateral oophorectomy (with or without 
hysterectomy) or tubal ligation at least 6 weeks ago. In 
case of oophorectomy alone, only when the reproductive 
status of the woman has been confirmed by follow up 
hormone level assessment is she considered not of child-
bearing potential. 
15. Active systemic infections during the 2 weeks prior to study 
drug initiation (exception: common cold) or any infection 
that reoccurs on a regular basis; investigator discretion 
should be used regarding patients who have traveled or 
resided in areas of endemic mycoses, such as histoplasmosis, 
coccidioidomycosis or blastomycosis and for patients with 
underlying conditions that may predispose them to infection, 
such as advanced or inadequately controlled diabetes. 


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16. Past medical history record of, or current infection at study 
drug initation with, human immunodeficiency virus (HIV), 
hepatitis B or hepatitis C.  
17. Chest X-ray, computerized tomography (CT scan), or 
Magnetic Resonance Imaging (MRI) with evidence of 
ongoing infectious or malignant process, obtained within 
12 weeks prior to investigational drug administration, and 
evaluated by a qualified physician. 
18. Serum creatinine level exceeding 2.0 mg/dL (176.8 μmol/L) 
at screening visit. 
19. Total white blood cell (WBC) count <2 500/μL, platelets 
<100 000/μL, neutrophils <1 500/μL or hemoglobin <8.5 
g/dL at screening visit. 
20. Patients with a history of hypersensitivity to latex. 
21. Forms of psoriasis other than plaque psoriasis (e.g., pustular 
psoriasis, palmoplantar pustulosis, erythrodermic and guttate 
psoriasis). 
Caution should be exercised when prescribing Cosentyx® to 
patients with Crohn’s disease as exacerbations of Crohn’s disease, in 
some cases serious, were observed in clinical studies in both 
Cosentyx® and placebo groups. Patients who are treated with 
Cosentyx® and have Crohn’s disease should be followed closely. 
Investigational and 
reference therapy 
The investigational drug, secukinumab AIN 457, is to be injected 
subcutaneously and will be provided by Novartis in pre-filled 
syringes (PFS) of 150 mg. Two injections will therefore be 
necessary to obtain the required dosage of 300 mg.  
The patient will be trained by the investigator or qualified personnel 
and will be encouraged to self-administer the injections at the 
investigation site at each visit until Week 16. Thereafter, the patient 
will be asked to self-administer the injection at the investigation site 
when attending a site visit (Weeks 24, 32, 40 and 48) or at home 
between visits (Weeks 20, 28, 36 and 44). If patient is not 
comfortable with self-injections, injections at home can be 
performed by a caregiver. 
 
Efficacy assessments 
The following patient-reported outcomes will be used: 
• ProPSI and saSPI. 
• PASI. 
• SA-PASI. 
• DLQI. 
• PSD (pain, itching, scaling). 


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Safety assessments 
• Adverse Events. 
• Physical examination. 
• Vital signs. 
• Hematology/Biochemistry. 
Other assessments 
• BISF-w/m (optional) 
•  
Populations 
The following analysis sets will be used in this study: 
• Included Set (IS): The included set will comprise all patients 
included in the study.  
• Full Analysis Set (FAS): The FAS will comprise all patients 
from the IS administered at least one dose of investigational 
drug during the treatment period with at least one Baseline 
and one post-Baseline SPI evaluation.  
• Safety Analysis Set (SAF): The SAF will comprise all 
patients administered at least one dose of investigational 
drug during the treatment period.  
• Per Protocol Set (PPS): The PPS will comprise all patients 
administered at least one dose of investigational drug during 
the treatment period without any major protocol deviation. 
Data analysis 
Primary analysis 
The primary variables for this study are the changes from Baseline 
of proSPI (s) and saSPI (s) at Week 16. 
The primary analysis of this study will be performed on the FAS 
population at Week 16 compared to Baseline and will be:  
• To evaluate the change from baseline of proSPI (s). 
• To evaluate the change from baseline of saSPI (s). 
The key secondary variable for this study is the PASI score. The key 
secondary analysis will be to assess PASI and to evaluate the 
correlation between PASI and proSPI (s) in the FAS. 
Statistical model, hypothesis, and method of analysis 
Summary statistics (mean, standard deviation, median, extreme 
values) will be presented for changes from Baseline to Week 16 
(proSPI (s), saSPI (s) and PASI) for all patients in the FAS.  
To assess the primary objective, the proSPI (s) and saSPI (s) will be 
analyzed using a paired t-test (baseline vs Week 16). The null 
hypothesis tested in this model is that there is no difference between 
means at baseline and Week 16.  
As there are co-primary endpoints an adjustment for multiplicity 


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will be performed using the Hochberg procedure and the family-
wise type-I-error will be set to α=5% (2-sided). The Hochberg 
procedure was chosen as the most powerful adjustment due to the 
positive association between proSPI (s) and saSPI (s) (L 
Chularojanamontri et al., 2013).  
The Hochberg procedure will be applied as follows, if the maximum 
of the two p-values is rejected at the 5% level (2-sided) then both 
hypotheses are rejected and statistical significance is claimed for 
both endpoints. Otherwise if the maximum of the 2 p-values is not 
rejected, then the minimum p-value is tested at the 2.5% level (2-
sided), if rejected then statistical significance is claimed just for this 
endpoint. 
In the event the data is non-normal the Wilcoxon signed rank test 
will be performed. 
Evolution of PASI score and PASI response during the study will be 
described and associated 95% CIs will be presented. Change from 
baseline to Week 16 of the PASI score will be analyzed as for the 
primary analysis. 
Spearman’s correlation coefficient and the associated test will be 
used to evaluate the correlation between PASI and proSPI (s). 
The same analysis will be performed on the PPS population as 
supportive. 
Secondary analysis 
Absolute values and change from baseline (at all assessment 
periods) for each SPI component will be described and analyzed as 
for the primary efficacy analysis. 
ProSPI (s) and saSPI (s) will be analyzed using a paired t-test. 
For each of the seven scores of the DLQI 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. Summary statistics will be provided for number of 
subjects achieving DLQI 0 or 1. 
Absolute values and change from baseline of the sa-PASI (at all 
assessment periods) will be described. 
For PSD, descriptive summary statistics will be presented for 
absolute values and change from baseline by visit for intensity of 
pain, itching and scaling. 
Relationships between scores will be explored using Spearman’s 
correlation coefficient and the associated test. 
Appropriate statistical tests performed on these secondary efficacy 


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variables will be detailed in the SAP. 
Exploratory analysis 
Correlations between saSPI and DLQI, between saSPI (s) and PASI, 
and between proSPI and saSPI (component s and p) will be 
evaluated using the Spearman correlation coefficient and the 
associated p-value. 
To explore sexual dysfunction, descriptive summary statistics will 
be presented for absolute values and change from baseline of BISF-
m and BISF-w scores. 
An analysis of the SPI responsiveness to change will be led in order 
to investigate if reductions in psoriasis severity resulting from 
treatment would be accompanied by corresponding reductions in 
proSPI–s and saSPI–s scores. This analysis will be performed by the 
calculation of receiver operating characteristic (ROC) area under the 
curve (AUC). 
Three criteria of response will be examined to evaluate each score: 
≥75, ≥90, and 100% reduction in PASI score. 
Safety analysis 
All safety evaluations will be performed on the SAF. 
Treatment-emergent adverse events (TEAEs: events starting after 
the first dose of investigational drug or events present prior to the 
first injection of investigational drug but with increased severity) 
will be summarized by PT.  
AEs will be summarized by presenting the number and percentage 
of patients with: 
• 
An AE. 
• 
An AE by primary SOC. 
• 
An AE by PT. 
Summaries will also be presented for AEs by severity and for 
investigational drug related AEs. If a patient reports more than one 
AE with the same PT, only the greatest severity will be presented for 
this AE. If a patient reports more than one AE within the same 
primary SOC, the patient will be counted only once with the highest 
severity at the SOC level, where applicable. 
All other information collected will be tabulated and listed as 
appropriate. 
Separate summaries will be provided for any death, SAE, any other 
significant AE leading to investigational drug discontinuation. 
These summaries will be presented for the whole study period.  


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Sample size calculation 
The sample size calculation is based upon the SPI variable which is 
the primary endpoint. 
A similar study by Chularojanamontri et al. J Inv dermatol 2013 
showed that it is possible to detect responsiveness and a minimum 
clinically important difference (an absolute change of 5 and 7 for 
proSPI (s) and saSPI (s), respectively) derived from PASI changes 
with n=100 patients. The study showed a standard deviation at week 
10 in change from baseline of 7.35 in proSPI (s) and 10.35 in saSPI 
(S) as the standard deviation at week 16 is expected to be higher, 
conservative standard deviation estimates of 14 and 19 will be 
assumed for change at week 16 for proSPI (s) and saSPI (s) 
respectively. 
Based on an analysis of paired differences, in order to have at least  
90% power to detect a significant clinical difference for each index 
at the 2.5% level (2-sided), it can be estimated that a sample size of 
100 evaluable patients would be sufficient. 
Taking into account an anticipated drop-out of 20 patients, 
120 patients will need to be included in the study. 
Key words 
Chronic moderate or severe plaque psoriasis, secukinumab, biologic, 
IL-17, AIN457, SPI, PASI.  


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1 
Introduction 
Chronic plaque psoriasis is a common inflammatory dermatosis that can have a profound 
impact on a patient’s life as it can cause major distress since it impacts on physical and 
psychological functioning. The skin lesions associated with plaque psoriasis are associated 
with significant symptoms, such as itching, pain and scaling, which can ultimately impact a 
patient’s emotional, social, occupational, and physical functioning (Chularojanamontri et al., J 
Inv Dermatol 2013, Lebwohl et al. Int J Dermatol 2013). Most commonly tools used to assess 
the severity and impact of psoriasis are the PASI (Psoriasis Area and Severity Index) and the 
DLQI (Dermatology Life Quality Index). Limitations of the PASI are inter-rater variability 
(Lebwohl et al. Int J Dermatol 2013, Ramsey & Lawrence, BJD 1991), requirement for 
cumbersome arithmetic that discourages most clinicians from using it in routine and modest 
correlation with Patient Reported Outcomes (PRO) and patient satisfaction (Schäffer et al. 
Eur J Dermatol 2010).  In addition, it does not take into account the importance of specific 
localizations (hands, feet, buttocks, genitals).  
Secukinumab (AIN457) is a human monoclonal antibody that selectively inhibits 
interleukin-17A. 
 
Outstanding response rates have been demonstrated in 
pivotal phase II and III studies (Rich et al., BJD 2012); Langley et al., NEJM 2014; Blauvelt 
et al., BJD 2014). Phase III development has used PASI and DLQI. 
In November 2014, the CHMP (Committee for Medical Products in Human Use) has granted 
a positive opinion including the following indication : “Cosentyx® is indicated for the 
treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic 
therapy”. 
Secukinumab is administered subcutaneously at a dosage of 300 mg per week during the 
induction phase (first month) and thereafter at a dosage of 300 mg per month. Such a regimen 
and dosage have been demonstrated to be the most efficient in patients in the pivotal studies 
(data on file). 
A new tool has been developed (Simplified Psoriasis Index: SPI), to provide a concise but 
holistic summary of psoriasis assessment. It has several advantages over current tools:  1) it 
evaluates specifically several critical localizations (scalp, face, hands, feet, anogenital skin); 
2) it is assessed by both the physician (proSPI component) and the patient (saSPI); and 3) it 
assesses psychological impact and includes historical features. The responsiveness to clinical 
changes measured using this tool has already been studied recently in patients initiating a new 
treatment for plaque psoriasis (Chularojanamontri et al., J Inv Dermatol 2013). 
This study will assess the changes from Baseline of SPI and its correlation with standard tests 
DLQI and PASI. 


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2 
Study objectives 
2.1 
Primary and key secondary objectives 
2.1.1 
Primary objective 
To evaluate the benefit of secukinumab on the severity of psoriasis based on the SPI 
(Simplified Psoriasis Index). This index comprises 3 components: severity (s), psychosocial 
(p) and intervention, (i) evaluated by both the physician (proSPI) and the patient 
(self-assessed: saSPI).  
Only the severity (s) component will be evaluated for the primary objective (both proSPI (s) 
and saSPI (s)). Changes at Week 16 compared to Baseline in patients suffering from moderate 
to severe plaque psoriasis will be analyzed. 
2.1.2 
Key secondary objectives 
• To assess PASI (weekly from week 0 to 4 then every 4 to 8 weeks until Week 56). 
• To evaluate correlation between PASI and proSPI (s).  
2.2 
Secondary objectives 
• To assess each component of proSPI (s, p and i) over time (weekly from Week 0 to 
4 then every 4 to 8weeks until Week 56). 
• To assess each component of saSPI (s, p and i) over time (weekly from Week 0 to 
4 then every 4 to 8 weeks until Week 56). 
• To assess DLQI over time (weekly from Week 0 to 4 then every 4 to 8 weeks until 
Week 56). 
• To assess self-administered PASI (SA-PASI) (weekly from Week 0 to 4 then every 
4 to 8 weeks until Week 56).  
• To assess pain, itching and scaling using the Psoriasis Symptom Diary 
questionnaire over time (weekly from Week 0 to 4 then every 4 to 8 weeks until 
Week 56). 
• To evaluate correlation between proSPI (for each component: s, p and i) and DLQI 
• To evaluate correlation between proSPI (for components p and i) and PASI 
• To evaluate safety during the treatment period (until the W52)  and during the 
extension treatment period (after the W52) 
 
2.3 
Exploratory objectives 
• To evaluate correlation between saSPI (for each component: s, p and i) and DLQI.  
• To evaluate correlation between proSPI and saSPI for components s and p. 
• To evaluate correlation between saSPI (s) and PASI. 
• To evaluate the ability of SPI to discriminate between responders and non-
responders based on PASI response. 


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• To explore sexual dysfunction using the Brief Index of Sexual Functioning 
(BISF-m or BISF-w) questionnaire (in a subset of subjects willing to complete 
sexual function questionnaire).  
3 
Investigational plan 
3.1 
Study design 
This is an open-label multicenter, single arm study in approximately 120 patients with 
moderate to severe psoriasis in approximately 20 centers in France. The study consists of four 
periods (Screening, Treatment, Extension and Follow-up) with a total of 15 visits, plus a 
maximum of 4 visits during the extension period.  
An initial one-month (maximum) screening period after screening visit allows wash-out of 
prohibited medications prior to starting the study. Eligible patients are scheduled to receive 
weekly injections of investigational drug during the first month (induction period), followed 
by monthly injections thereafter to Week 16. The primary objective will be assessed at 
16 weeks prior to the administration of investigational drug at this visit. The patient will then 
continue with monthly injections until Week 48 in case of a favorable response to treatment at 
week 16 (cf §3.1.2). Treatment should last a maximum of 12 months. Patients will be 
monitored over a further eight weeks with an End of treatment visit at Week 52.  
Patients eligible for the extension period, i.e. having received their injection of study drug at 
W48 before Cosentyx® is marketed in France, will enter an extension period until 3 January 
2017 or until commercialization of Cosentyx® in France, whichever occurs first. LPLV will 
be no later than 3 January 2017, therefore the last possible administration of secukinumab 
during the study can be 3 November 2016 at the latest, whether Cosentyx® is commercialized 
or not. 
Patients who have received their last injection (W48) after secukinumab is marketed in France 
will complete the study as initially planned (EOT visit at W52 and Follow-up visit at W56). 
For patients who discontinue study treatment prematurely for any reason during the treatment 
or extension treatment periods, or for patients who finished the extension treatment period, 
End of Treatment (EoT) or End of Extension (EOE) visits should be performed 4 weeks after 
the last administration of study drug. In addition a Follow-up (FU) visit should be performed 
8 weeks after the last administration of study drug. An outline of the study design is presented 
in Table 6.1. 
 


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Figure 3-1 
Study design 
 
 
 
 
 
  


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3.1.1 
Screening period 
Between screening visit (assessment of patient eligibility) and first s.c. injection with 
secukinumab 300 mg, there is a screening period of 7 to 28 days for wash-out of prohibited 
medications (detailed in Section 5.5.9). 
 
Baseline assessments should be performed prior to the first study treatment administration, i.e. 
at Week 0 and Visit 1. 
3.1.2 
Treatment period 
During the treatment period, patients will initially attend five weekly visits (induction period), 
each with a s.c. injection of secukinumab 300 mg. Three subsequent monthly injections to 
Week 16 are planned. The primary and key secondary endpoints will be assessed at Week 16, 
prior to injection at this visit. If the investigational drug is judged by the investigator and 
patient to be beneficial to the patient, the response to treatment will be considered to be 
favorable and monthly injections will continue to Week 48. In the absence of a favorable 
response at Week 16, the investigational drug will be discontinued and the patient should 
attend End of Treatment visit and will then enter the follow-up period (after EOT visit, the 
investigator will discuss with the patient the best treatment options). The maximum duration 
of the treatment period is approximately 12 months (not including follow up) and the 
maximum number of sits visits is 12. 
Patients who discontinue the investigational drug prematurely for any reason (other than 
withdrawal of informed consent) should performed the End of Treatment visit 4 weeks after 
last injection of investigational drug and enter the post-treatment follow-up period. 
 
3.1.3 
Extension period 
 
Eligible patients who have received their injection of study drug at W48 before Cosentyx® is 
marketed in France will enter the extension period until 3 January 2017 or until 
commercialization of Cosentyx® in France, whichever occurs first.  
During this extension they will continue to receive monthly injections until End of Extension 
visit. They will continue to attend the study site every 2 months and self-inject study drug at 
home between site visits. In case the commercialization is announced as imminent, subjects 
will be asked to return at study site on the date of the next scheduled injection where they will 
receive their last injection of study drug. They will then return to the site for the EOE and 
follow-up visits. 
The maximum duration of the extension period is approximately 8 months (including follow 
up), assuming that the current date of First Patient Last Treatment (FPLT) is expected in May 
2016 and the latest possible date for Last Patient Last Visit is 3 January 2017. The potential 
maximum number of site visits is 4: three visits every 2 months (with study drug 
administration) and the End of Extension visit planned 4 weeks after last study drug 
administration. LPLV will be no later than 3 January 2017, therefore the last possible 
administration of secukinumab during the study can be 3 November 2016 at the latest, 
whether Cosentyx® is commercialized or not. 


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For patients who discontinue study treatment prematurely for any reason (other than 
withdrawal of informed consent) during the extension treatment period or patients who finish 
the extension treatment period, End of Extension (EoE) visit should be performed 4 weeks 
after the last administration of study drug.  
 
3.1.4 
Follow-up period 
All patients should attend an End of Extension visit, even if they do not complete the study for 
any reason (other than withdrawal of inform consent), in order to collect safety data. 
For all patients, a Follow-up visit should be performed 8 weeks after the last administration of 
study drug. 
 
3.2 
Rationale of study design 
The design of this study, including the extension treatment period, is based on previous Phase 
III trials and published data for the treatment of psoriasis with secukinumab. The primary 
endpoint will be assessed at Week 16 (Visit 8) and efficacy and safety will be monitored at 
each visit. However, patients should continue treatment with investigational drug for a further 
32 weeks (8 more injections between Weeks 16 and 48: Visits 9 to 12). Patients who are 
deemed to be benefiting from the study drug after 48 weeks of treatment could be 
continuously treated until 3 November 2016 or until commercialization of Cosentyx® in 
France, whichever occurs first. 
There will be an End of Treatment visit at Week 52, an End of Extension visit four weeks 
after last injection of study drug and a Follow-up visit in order to collect efficacy and safety 
data related to the long-term administration of secukinumab. 
 
3.3 
Rationale of dose/regimen, route of administration and duration 
of treatment 
The dose of secukinumab chosen in this study (2 x 150 mg injection; 300 mg) is the dose 
which combines maximum efficacy with maximum safety. There will be an initial induction 
phase (weekly injections) before switching to monthly injections, with a follow-up period in 
order to monitor the long-term efficacy and safety of secukinumab 300 mg administration. 
These schedules are in keeping with previous studies (for psoriasis and other indications such 
as rheumatoid arthritis) and are not expected to give rise to any safety concerns. The s.c. route 
was chosen for injection in this study (to facilitate patient self-administration). Details are 
provided in the Cosentyx Summary of Product Characteristics.   
3.4 
Rationale for choice of comparator 
Not applicable since this is a study with a single arm. 
3.5 
Purpose and timing of interim analyses/design adaptations 
No interim analysis is planned in this study. 


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3.6 
Risks and benefits  
 
 
 
 
 
 
 Full safety results including all reported AEs are currently available for 
several completed studies across different indications. In general, these show comparable 
numbers of AEs in patients treated with secukinumab compared to placebo without indication 
of any specific organ toxicity. The Cosentyx Summary of Product Characteristics provides a 
more detailed review of the pre-clinical and clinical information related to secukinumab. 
At the time of finalization of this protocol, safety data including AE data, laboratory 
parameters, available immunogenicity data from the completed studies and SAE data from the 
ongoing larger studies have not highlighted any individual safety risk or particular pattern of 
event clustering. Any future changes to benefit/risk ratio resulting from data that becomes 
available from the Phase III studies will be communicated as needed and appropriate (e.g. via 
the Cosentyx Summary of Product Characteristics). 
In common with other biologic immune modulators, secukinumab has the potential to 
interfere with the immune response to infections. Thus, continuing vigilance will be applied 
with respect to capturing all information concerning treatment-emergent infections or 
infestations. A number of different infections have been reported for patients receiving 
secukinumab and these are summarized in the Cosentyx Summary of Product Characteristics. 
 
 
 
 Taking into account all AE data from the completed 
studies and SAE data from ongoing studies, no specific pattern of infection, or a specific 
pathogen involved, has been identified as clearly prevalent.  
The effect of secukinumab on vaccination has been evaluated in a study in adult healthy 
volunteers exposed to a single 300 mg s.c. dose of secukinumab in addition to vaccination 
with the influenza and meningococcus vaccines 
 
 
 
 administration of a single 300 mg dose 
of secukinumab in adult healthy volunteers vaccinated with influenza and meningitis C 
vaccines does not impair the efficacy of the immune response to these vaccines. 
 
 
 
Live vaccines 
should not be administered in patients exposed to secukinumab. 
Patients with pre-existing malignancies within the past 5 years are generally excluded from 
studies with secukinumab, although there is no scientific evidence to suggest that 
secukinumab would increase the risk for malignancies. 


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Based upon the results of toxicology studies which demonstrated a lack of effect of 
secukinumab on fertility and embryo-fetal development, women of child-bearing potential can 
be included in studies with secukinumab, however, pregnancy must be prevented by proven 
effective measures. No contraceptive measures are required for males participating in studies 
with secukinumab. 
In summary, the expected risk profile of secukinumab from a mechanism of action 
perspective is anticipated to be similar to or improved compared to approved 
cytokine-targeting therapies. 
 
 
The risk to patients in this trial will be minimized by compliance with the eligibility criteria 
and close clinical monitoring. 
All quality, non-clinical pharmacology and toxicology data, as well as the available clinical 
efficacy and safety data for secukinumab are considered sufficient to expect a positive 
benefit/risk ratio for the treatment of moderate to severe plaque psoriasis with secukinumab. It 
is therefore considered appropriate to initiate this study. 
On 21 November 2014, Novartis received Cosentyx® positive CHMP (Committee for 
Medical Products in Human Use) opinion for the first-line treatment of moderate to severe 
psoriasis patients. This opinion states that PASI 90, PASI 100 and IGA 0/1 response rates 
were statistically significantly better with Cosentyx® compared to placebo. Moreover, 
Cosentyx® was statistically significantly superior to Etanercept in systemic treatment naive, 
biologic-naive, biologic/anti-tumour necrosis factor (TNF)-exposed and biologic/anti-TNF-
failure patients. Finally, most of the reactions were mild or moderate in severity. The 
proposed indication is: “Cosentyx® is indicated for the treatment of moderate to severe 
plaque psoriasis in adults who are candidates for systemic therapy”. 
 
4 
Population 
The study population will consist of adult male and female out-patients (≥ 18 years old) with a 
history of moderate to severe plaque psoriasis for at least 6 months before the screening visit 
and who are candidates for systemic therapy. Patient may either have received previous 
biotherapy or be biological naïve. At screening visit, patients need to have the following 
scores: PASI ≥ 12; Body Surface Area: BSA ≥ 10 and Investigator Global Assessment: IGA 
mod 2011 ≥ 3. At baseline visit, patients need to have a PASI score ≥ 12. 
It is planned to include a total of approximately 100 patients in around 20 centers. 
Anticipating a drop-out of 20 patients, approximately 120 patients will need to be screened.  
4.1 
Inclusion criteria 
Patients eligible for inclusion in this study have to fulfill all of the following criteria: 
1. 
Patients aged ≥ 18 years old at the Screening visit. 
2. 
Patients with a history of chronic moderate to severe plaque psoriasis for at least 6 
months before the Screening visit. 
Furthermore, patients need to have the following scores:  


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• PASI ≥ 12, BSA ≥ 10 and IGA mod 2011 ≥ 3 at Screening visit and  
• PASI ≥ 12 at Baseline visit 
3. 
Patients candidates for systemic therapy.  
4. 
Patients able to understand and communicate with the investigator and comply with the 
requirements of the study (including administration of s.c. injections at home), capable of 
and willing to complete several questionnaires at visits, and must provide written, signed 
and dated informed consent before any study related activity is performed. 
5. For the extension period (patients who received their injection of study drug at W48 
before Cosentyx® is marketed in France): favorable clinical benefit of study treatment as 
judged by the investigator and patient. Patient willing to continue receiving secukinumab. 
 
4.2 
Exclusion criteria 
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No 
additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible patients. 
1. Patients with a history of hypersensitivity to the study drug or to drugs of a similar 
chemical class. 
2. Patients with recent (previous 6 weeks) or planned vaccination with live virus. 
3. Patient participation in another clinical study during the 4 weeks prior to study drug 
initiation or 5 half-lives (whichever is the longest). 
4. Patients taking other drugs for psoriasis (e.g. corticosteroids, vitamin D analogs, 
pimecrolimus, retinoids, salicylvaseline, salicylic acid, lactic acid, tacrolimus, tar, 
urea, α-hydroxy or fruit acids). 
5. Patients suffering from a skin condition other than moderate to severe plaque psoriasis 
that may confound psoriasis evaluation, or other inflammatory disease. 
6. Patients suffering from drug-induced psoriasis (e.g. new onset or current exacerbation 
by beta-blockers, calcium channel inhibitors, or lithium), as judged by investigator. 
7. Patients with underlying condition(s) (including, but not limited to metabolic, 
hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiovascular (eg: 
heart failure NYHA class III or IV, unstable angina….), infectious,  gastrointestinal or 
psychiatric) 
which 
in 
the 
opinion 
of 
the 
investigator 
significantly 
immunocompromises the patient and/or places the patient at unacceptable risk for 
receiving an immunomodulatory therapy). 
8. Patients with previous treatment with any agent targeting Interleukin (IL)-17 directly 
or IL-17 receptor (e.g. secukinumab, ixekizumab, or brodalumab).  
9. Patients refusing to limit sunlight or Ultraviolet (UV) light exposure. 
10. Patients unwilling to be subjected to repeated s.c. injections and venipuncture.  
11. History of an ongoing, chronic or recurrent infectious disease, or evidence of 
tuberculosis (TB) infection as defined by a positive or indeterminate QuantiFERON 
TB-Gold test (QFT) at screening visit. Patients with a positive QFT test may 
participate in the study if a full tuberculosis work up (according to local 
practice/guidelines) completed at least 12 weeks prior to study drug initiation 


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establishes conclusively that the patient has no evidence of active tuberculosis. If the 
presence of latent tuberculosis is established, then treatment must have been initiated 
and maintained according to guidelines for at least 4 weeks prior to study drug 
initiation. 
12. History of lymphoproliferative disease or any known malignancy or history of 
malignancy of any organ system within the past 5 years (except for skin Bowen’s 
disease, or basal cell carcinoma or actinic keratoses that have been treated with no 
evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or 
non-invasive malignant colon polyps that have been removed). 
13. 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). 
14. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using highly effective methods of contraception 
during dosing of study treatment and for 20 weeks after stopping treatment. Highly 
effective contraception methods include: 
• Total abstinence: when this is in line with the preferred and usual lifestyle of the 
subject. 
Periodic 
abstinence 
(e.g. 
calendar, 
ovulation, 
symptothermal, 
post-ovulation methods) and withdrawal are not acceptable methods of 
contraception. 
• Female sterilization: have had surgical bilateral oophorectomy (with or without 
hysterectomy) or tubal ligation at least 6 weeks before taking study 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. 
• Combination of any two of the following methods (a+b or a+c or b+c): 
 
a. Use of oral, injected or implanted hormonal methods of contraception or other 
forms or hormonal contraception that have complete efficacy (failure <1%), e.g. 
hormone vaginal ring or transdermal hormone contraception. 
 
b. Placement of an intrauterine device (IUD) or intrauterine system (IUS). 
 
c. Barrier methods of contraception: condom or occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.  
 
In case of use of oral contraception, women should have been stable on the same 
pill for a minimum of 12 weeks before taking study treatment.  
 
NOTE: Women are considered post-menopausal and not of child-bearing potential 
if they have had:  
• 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile 
(e.g. age appropriate, history of vasomotor symptoms). 
• Surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at 
least 6 weeks ago. In case of oophorectomy alone, only when the reproductive 
status of the woman has been confirmed by follow up hormone level assessment is 
she considered not of child-bearing potential. 


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15. Active systemic infections during the 2 weeks prior to study drug initiation (exception: 
common cold) or any infection that reoccurs on a regular basis; investigator discretion 
should be used regarding patients who have traveled or resided in areas of endemic 
mycoses, such as histoplasmosis, coccidioidomycosis or blastomycosis and for 
patients with underlying conditions that may predispose them to infection, such as 
advanced or inadequately controlled diabetes. 
16. Past medical history record of, or current infection at study drug initation with, human 
immunodeficiency virus (HIV), hepatitis B or hepatitis C.  
17. Chest X-ray, computerized tomography (CT scan), or Magnetic Resonance Imaging 
(MRI) with evidence of ongoing infectious or malignant process, obtained within 
12 weeks prior to investigational drug administration, and evaluated by a qualified 
physician. 
18. Serum creatinine level exceeding 2.0 mg/dL (176.8 μmol/L) at screening visit. 
19. Total white blood cell (WBC) count <2 500/μL, platelets <100 000/μL, neutrophils 
<1 500/μL or hemoglobin <8.5 g/dL at screening visit. 
20. Patients with a history of hypersensitivity to latex. 
21. Forms of psoriasis other than plaque psoriasis (e.g., pustular psoriasis, palmoplantar 
pustulosis, erythrodermic and guttate psoriasis). 
 
Caution should be exercised when prescribing Cosentyx® to patients with Crohn’s disease as 
exacerbations of Crohn’s disease, in some cases serious, were observed in clinical studies in 
both Cosentyx® and placebo groups. Patients who are treated with Cosentyx® and have 
Crohn’s disease should be followed closely. 
 
5 
Treatment 
5.1 
Protocol requested treatment 
5.1.1 
Investigational drug 
The investigational drug, secukinumab AIN 457, is to be injected subcutaneously and will be 
provided by Novartis in pre-filled syringes (PFS) of 150 mg. Two injections will therefore be 
necessary to obtain the required dosage of 300 mg.  
5.1.2 
Additional study treatment 
No additional treatment. 
5.2 
Treatment arms 
The study is a single arm study.  
5.3 
Treatment assignment, randomization  
Since this is an open label single-arm study, there will be no randomization for this study. 


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5.4 
Treatment blinding  
Since this is an open label single-arm study, treatment blinding will not be necessary. 
5.5 
Treating the patient 
5.5.1 
Patient numbering  
Each patient is uniquely identified by a patient number which is composed by the site number 
assigned by Novartis and a sequential number assigned by the investigator. Once assigned to a 
patient, the patient number will not be reused.  
Upon signing the Informed Consent Form (ICF), the patient is assigned the next sequential 
number as given by the investigator using the next blank CRF book available from the EDC 
system.  
5.5.2 
Dispensing the investigational treatment 
Novartis will supply each study site with investigational drug: Secukinumab 300 mg, 
provided in two PFS of 1 mL each, labeled with the study number. 
5.5.3 
Handling of study drug 
5.5.3.1 
Handling of investigational drug 
Investigational drug must be received by a designated person at the study site, handled and 
stored safely and properly, and kept in a secured location to which only the investigator and 
designees have access. Upon receipt, investigational drug should be stored according to the 
instructions specified on the label. Clinical supplies are to be dispensed only in accordance 
with the protocol. 
The PFS (150 mg secukinumab) sealed in their outer box must be stored in a locked 
refrigerator between 2°C and 8°C (36°F and 46°F, DO NOT FREEZE) and must be carefully 
controlled in accordance with regulations governing investigational medicinal products and 
local regulations. 
Medication labels will be in French in compliance with legal requirements. They will include 
storage conditions for the investigational drug but no information about the patients. 
The investigator must maintain an accurate record of the shipment and dispensing of 
investigational drug in a drug accountability log. Monitoring of drug accountability will be 
performed by the field monitor during site visits and at the completion of the trial. Patients 
will be asked to return all unused investigational drug and packaging at the end of the study or 
at the time of discontinuation of investigational drug.  
At the conclusion of the study, and as appropriate during the course of the study, the 
investigator will return all unused investigational drug, packaging, drug labels, and a copy of 
the completed drug accountability log to the Novartis monitor or to the Novartis address 
provided in the investigator folder at each site. 


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5.5.3.2 
Handling of other study treatment 
Not applicable. 
5.5.4 
Instructions for prescribing and taking investigational drug 
5.5.4.1 
Treatment administration 
Two PFS of 150 mg secukinumab will be necessary for each injection (total dose: 300 mg). 
Investigational drug administration will be either weekly or monthly as described in 
Section 5.5.4.2. 
Secukinumab must be injected subcutaneously in non-affected areas of the skin preferably 
to one of the following body regions: front of thighs, lower abdomen (but not the area 
2 inches around the navel (belly button)) or outer upper arms. A different site should be used 
for each injection. Secukinumab should not be injected into areas where the skin is tender, 
bruised, red, scaly or hard, and areas with scars or stretch marks should be avoided. As far as 
possible, the injection site should be changed from administration to administration, 
throughout the study.  
The patient will be trained by the investigator or qualified personnel and will be encouraged 
to self-administer the injections at the investigation site at each visit until Week 16. 
Thereafter, the patient will be asked to self-administer the injection at the investigation site 
when attending a site visit (Weeks 24, 32, 40 and 48) or at home between visits (Weeks 20, 
28, 36 and 44 during the treatment period and Weeks 60 and 68 during the extension period). 
If patient is not comfortable with self-injections, injections at home can be performed by a 
caregiver. 
All injections must be documented in self-administration log. 
All dosages prescribed and dispensed to the patient and any dose or schedule modification 
during the study must be recorded on the Dosage Administration Record CRF. 
 
5.5.4.2 
Treatment periods 
There are 3 treatment periods:  
• A 4-week induction phase with weekly injections at the investigational site. 
• A 12-week treatment period with monthly injections at the investigational site. 
• A 32-week treatment period with monthly injections at the investigation site when 
attending a visit (Weeks 24, 32, 40 and 48) or at home between visits (Weeks 20, 28, 
36 and 44). 
The primary criterion will be evaluated at the end of the 12-week treatment period (i.e. at 
Week 16). If the investigational drug is judged by the investigator and patient to be beneficial 
to the patient, the response to treatment will be considered to be favorable and monthly 
injections will continue to Week 48. In the absence of a favorable response at Week 16, the 
investigational drug will be discontinued and the patient should attend End of Treatment visit 


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and will then enter the follow-up period (after EOT visit, the investigator will discuss with the 
patient the best treatment options).  
5.5.5 
Extension period 
An extension period (only for patient who have received their injection of study drug at W48 
before Cosentyx® is marketed in France): period with monthly injections, every 2 months at 
the investigation site when attending a visit (Weeks 56, 64 to (maximum) 72, visits E1, E2 to 
(maximum) E3 or at home between visits (Weeks 60 and (maximum) 68). 
If the investigational drug is judged by the investigator and patient to be beneficial to the 
patient, the response to treatment will be considered to be favorable and monthly injections 
will continue during the extension period. LPLV will be no later than 3 January 2017, 
therefore the last possible administration of secukinumab during the study can be 3 November 
2016 at the latest, whether Cosentyx® is commercialized or not. 
In case the commercialization is announced as imminent, subjects will be asked to return at 
study site on the date of the next scheduled injection where they will receive their last 
injection of study drug. They will then return to the site for the EOE and follow-up visits. 
In the absence of a favorable response at any time during the extension period, the 
investigational drug will be discontinued and the patient should attend End of Extension visit 
and will then enter the follow-up period (after EOE visit, the investigator will discuss with the 
patient the best treatment options). 
5.5.6 
Permitted dose adjustments and interruptions of investigational drug 
Investigational drug dose adjustments are not permitted during this study. 
Temporary interruption of investigational drug is permitted in order to keep the patient on the 
investigational drug if, in the opinion of the investigator, a patient is deemed to be placed at a 
safety risk unless dosing is temporarily interrupted. In such cases the investigational drug 
should be interrupted for only the period when this risk is present and on-going. The 
investigational drug can be resumed at the next scheduled visit when the investigator 
considers that there is no further safety risk. 
The effect of secukinumab on live vaccines is unknown, therefore, live vaccines should not be 
administered during the study. Any patient receiving a live virus vaccination during the study 
must discontinue investigational drug and enter the post-treatment follow-up period.  
Any interruption, temporary or permanent must be recorded on the Dosage Administration 
Record CRF. 
5.5.7 
Rescue medication 
Rescue medication is not permitted in this study. 
5.5.8 
Prior and concomitant treatment 
All treatments administered during the 6 months prior to start of study treatment (including 
any treatments started during the screening period) will be entered in the eCRF.  


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All systemic treatments and phototherapies for psoriasis administered prior to screening visit 
will be entered in the eCRF.  
The investigator should instruct the patient to notify the study site about any new medications 
he/she takes after the patient was enrolled into the study. All medications,  administered after 
the patient was enrolled in the study must be recorded. 
5.5.8.1 
Concomitant medication permitted for psoriasis treatment 
Concomitant medication for psoriasis treatment is restricted to bland emollients (not supplied 
by Novartis) and other non-medicated interventions if not listed in Table 5-1. If the patient 
experiences intolerable scaling and/or itching after study drug initiation, the use of bland 
emollients is permitted but must be avoided during the 12 hours preceding a scheduled study 
visit/injection. Dose adjustment of any concomitant medication should be avoided during the 
study and any necessary dose adjustment must be recorded in the eCRF. 
A mild to moderate potency topical corticosteroid (TCS) will be allowed for treatment on the 
face, scalp and the anogenital area during the Screening period but must be stopped the day 
before the first treatment with the investigational drug.  
Anti-histamines and inhaled, ocular or auricular corticosteroids are permitted. 
5.5.8.2 
Concomitant medication permitted for other conditions 
Concomitant medications are allowed if not listed in Table 5-1. Dose adjustment should be 
avoided during the study and, if necessary, must be recorded in the eCRF. 
Any treatment known to worsen psoriasis (e.g. beta-blockers, calcium channel blockers, 
lithium) must be stable for at least 4 weeks prior to study drug initation and throughout the 
study. 
5.5.8.3 
Concomitant medication permitted for psoriatic arthritis 
Concomitant medications for psoriatic arthritis are allowed if not listed in Table 5-1. Dose 
adjustments of these medications should be avoided during the study and, if necessary, must 
be recorded in the eCRF. 
5.5.9 
Prohibited Treatment 
The use of any of the treatments displayed in Table 5-1, or non-respect of the respective 
wash-out period before starting investigational drug, that could confound efficacy are 
prohibited during the study for any indication. If any of these treatments are planned the 
patient cannot participate in the study. 
Patients having had previous treatment with any agent targeting IL-17 directly or its receptor 
(including secukinumab) cannot participate in the study. During the study, only secukinumab 
will be allowed. 
There must be a 7 to 28-day (±2 days) wash-out period after screening visit prior to start of 
investigational drug. If this period is not respected, the patient cannot be injected with the 
investigational drug. Use of any of the listed prohibited medications is NOT allowed after the 
first injection with the investigational drug. The patient should be instructed to notify the 
study site about any new treatments he/she takes after the start of the investigational drug. All 


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prohibited medications and significant non-drug therapies administered after the patient starts 
investigational drug must be recorded in the eCRF. Any patient receiving a prohibited 
medication during the study must discontinue the investigational drug and enter the 
post-treatment follow-up period. 
Patients should be advised to limit exposure to UV light (including sunbathing and/or use of 
UV tanning devices) during the study to avoid any possible effect on psoriasis. 
Administration of a live vaccine during the study will lead to permanent discontinuation of 
investigational drug and the patient should enter the post-treatment follow-up period. Other 
types of vaccination should be avoided during the study. 
Table 5-1 
Prohibited treatment 
 
Treatment1, 2 
Wash-out period prior to 
injection of investigational drug 
Biologic agents targeting IL-17 directly or IL-17 
receptor (including secukinumab)  
No prior use allowed 
Other biologic immunomodulating agents:  
           Alefacept, briakinumab, efalizumab,      
           ustekinumab 
           Adalimumab, etanercept, infliximab 
 
6 months 
 
12 weeks 
Other systemic immunomodulating treatments (e.g. 
methotrexate, cyclosporine A, corticosteroids3 (oral, 
i.v., i.m., s.c., intra-articular, transdermal), 
cyclophosphamide) 
 
4 weeks 
Other systemic psoriasis treatments  (e.g. retinoids, 
fumarates) 
4 weeks 
Photochemotherapy (e.g. PUVA) 
4 weeks 
Phototherapy (e.g. UVA, UVB) 
2 weeks 
Topical treatments likely to impact on signs and 
symptoms of moderate to severe psoriasis 
(e.g. corticosteroids4, vitamin D analogs, 
pimecrolimus, retinoids, salicylvaseline, salicylic 
acid, lactic acid, tacrolimus, tar, urea, α-hydroxy or 
fruit acids) 
 
2 weeks 
Live virus vaccination 
6 weeks 
Any investigational treatment or participation in any 
interventional trial 
4 weeks or 5 half-lives 
(whichever is the longer) 
Any treatment known to worsen psoriasis  
Stable at least 4 weeks before 


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Treatment1, 2 
Wash-out period prior to 
injection of investigational drug 
(e.g. ß-blockers, calcium channel blockers, lithium) 
Study drug initiation 
Prohibited regimen of topical corticosteroids 
(TCS) 
 
TCS with higher than moderate potency 
2 weeks 
TCS with mild to moderate potency on any body 
location other than the face, scalp and/or anogenital 
area 
 
2 weeks 
 
TCS with mild to moderate potency on face, scalp 
and/or anogenital area 
1 day 
1  If the prohibited treatment was used during the study, the patient must discontinue use of prohibited 
treatment if he/she wishes to continue in the study 
2  In case of undue safety risk for the patient, the patient should discontinue study treatment at the discretion of 
the investigator. If the patient received a live virus vaccination during the study, the patient must discontinue 
study treatment 
3  Inhaled CS with only a topical effect (e.g. to treat asthma) are not considered as ‘systemic 
immunomodulating treatments’ and are therefore acceptable as concomitant medication 
4   Mild to moderate topical CSs are allowed only during the Screening period if used only on the face, scalp 
and/or anogenital area. These topical CSs must be stopped 12 hours prior to first injection.  
After Week 16 and if clinically needed, TCSs are allowed during the study for short-term use (<14 days), for 
non-psoriasis indications and on areas not affected by psoriasis (see Section 5.5.8) 
The use of certain medications will be allowed at the investigator’s discretion or for a 
restricted duration or specific dose (refer to Section 5.5.8). 
5.5.10 
Discontinuation of investigational drug and premature patient 
withdrawal 
Patients may voluntarily withdraw from the study for any reason at any time. Patients will be 
considered as withdrawn if they state an intention to withdraw, fail to return for visits, or 
become lost to follow-up for any other reason. If premature withdrawal occurs for any reason 
(including during the post-treatment follow-up period), the investigator must make every 
effort to determine the primary reason for a patient’s premature withdrawal from the study 
and record this information in the eCRF. The investigational drug must be discontinued.  
The investigator should discontinue the investigational drug for a given patient if he/she 
believes that continuation would be detrimental to the patient’s well-being.  
The investigational drug must be discontinued and the patient withdrawn from the study under 
the following circumstances:  
• Emergence of any Adverse Event (AE) judged by the investigator to prevent the patient 
from continuing treatment. 
• Any of laboratory abnormality judged by the investigator to prevent the patient from 
continuing treatment. 


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• Pregnancy. 
• Any deviation from the prescribed dose regimen of the investigational drug.  
• Use of prohibited treatment listed in Table 5-1 and that presents undue safety risk. 
• Any other protocol deviation that results in a significant risk to patient safety. 
• Any situation in which investigator considers that continuation is not beneficial to the 
patient. 
In all cases, the patient should enter the post-treatment follow-up period with at least an End 
of treatment visit 4 weeks after last administration of investigational drug. 
For patients who are lost to follow-up (i.e. those patients whose status is unclear because they 
fail to appear for study visits without stating an intention to withdraw), the investigator should 
show ‘due diligence’ by documenting in the source documents steps taken to contact the 
patient, e.g. dates of telephone calls, registered letters, etc. 
Patients who are prematurely withdrawn from the study will not be replaced by an equal 
number of newly enrolled patients. 
5.5.11 
Emergency breaking of treatment assignment 
Not applicable since this is a single-arm study with no randomization to a treatment group. 
5.5.12 
Study completion and post-study treatment 
Study completion is defined as all patients included at Baseline who completed the study as 
described in the protocol. 
The investigator must provide follow-up medical care for all patients who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care.  
5.5.13 
Early study termination 
The study can be terminated at any time for any reason by Novartis. Should this be necessary, 
the patient should be seen as soon as possible and treated as a prematurely withdrawn patient. 
The investigator may be informed of additional procedures to be followed in order to ensure 
that adequate consideration is given to the protection of the patient’s interests.  
6 
Visit schedule and assessments 
All assessments to be performed are listed in Table 6-1indicated with an ‘x’ at the visits when 
they should be performed. 
Fifteen (15) visits are planned during the study: an initial Screening visit around one month 
prior to treatment administration to check eligibility, to obtain signed informed consent and to 
ensure a wash-out period for prohibited medications, 12 visits during the treatment period and 
two visits during the follow-up period: an End of treatment visit and a Follow-up visit. 
Patients should be seen for all visits as per assessment schedule. Injections at the 
investigational site, preferably by the patient, are planned at Visit 1 to Visit 8 and the 


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injections should be performed by the patient at home (Weeks 20, 28, 36 and 44) or on site 
(Weeks 24, 32, 40 and 48), after W16 as per assessment schedule. The authorized ‘visit 
windows’ are as follows: 
• Screening (Visit 0) to Visit 1 (1st injection): 1 to 4 weeks ±2 days. 
• From Visit 1 (Week 0) until Visit 5 (Week 4): 1 week ±2 days. 
• From Visit 6 (Week 8) until Visit 8 (Week 16): 4 weeks ±2 days. 
• From Week 20 to Visit 12 (last injection at Week 48): 4 weeks ±5 days. Same visit 
window will apply to the Extension period. 
• After Week 48 (or Week (maximum) 72 for patient entering the extension period), 
there will be two more visits during the follow-up period: End of treatment visit at 
Week 52 and Follow-up visit at Week 56 (or End of Extension and Follow-up visits, 
respectively, 4 and 8 weeks after the last administration of study drug, for patient 
entering the extension period), each with a ‘visit window’ of 4 weeks ±5 days. 
In addition, during treatment, patients may be seen at an unscheduled visit, e.g. if they 
experience deterioration of psoriasis or suspected AEs. During these unscheduled visits, 
investigational drug will NOT be administered. 
Patients who discontinue the investigational drug should enter the post-treatment follow-up 
period with at least an End of treatment visit four weeks after last injection. If they refuse to 
return for an assessment or are unable to do so, every effort should be made to contact them or 
a knowledgeable informant by telephone. Documentation of attempts to contact the patient 
should be recorded in the patient source documentation.  
The reason for discontinuation/withdrawal should be obtained and safety data since the last 
study visit or since the last administration of investigational drug should be collected if they 
do not attend any post-treatment follow-up visit.  
6.1 
Information to be collected on screening failures 
If for any reason a patient is a screen failure, the patient may be rescreened. There is no 
restriction on the number of times a potential patient may be rescreened or on how much time 
must pass from the date of screen failure and the date of rescreening. 
All patients providing signed informed consent but not entering the treatment period will have 
Screening visit data collected: demographics, inclusion/exclusion criteria and Serious Adverse 
Events (SAE) data. AEs that are not SAEs will be followed-up by the investigator and 
reported only in the source data. 
All patients providing signed informed consent and entering the treatment period (with at least 
one Cosentyx® administration) of the study will have all AEs occurring after signature of 
informed consent recorded on the Adverse Event CRF. 
Investigators will have the discretion to record abnormal test findings on the Medical History 
CRF whenever in their judgment, the test abnormality occurred prior to the informed consent 
signature. 
 


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Table 6-1 
Assessment schedule 
Period 
Screening 
Treatment1 
End of 
treatment 
Extension 
Treatment 
15 
End of 
Extension 
16 
Follow-
up 17 
 
 
Unscheduled 
visit3 
 
 
Period 1 
Period 22 
Visit 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 12 
13 
E1, E2 
and E3 
 
 
Week 
≥- 4 to ≤-1 
0 
1 
2 
3 
4 
8 
12 16 24 
32 
40 48 
52 
56, 64 and 
72 
 
80 
maximum 
Visit window (days) 
±2 
 
±2 
±2 
±2 
±2 
±2 ±2 ±2 ±5 
±5 
±5 ±5 
±5 
±5 
±5 
±5 
Inclusion/Exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Please 
see 
details in 
Table 6-2 
 
 
 
Demographics4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relevant medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Psoriasis medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous treatment for 
psoriasis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Smoking history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Education level 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Previous medication 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medication 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
QuantiFERON® TB-Gold In-
Tube test6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X3 
Chest X-ray, MRI or CT-
scan7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BSA8 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IGA8 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy 
test9: 
Blood 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X3 
Biochemistry10 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
Hematology11 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
 


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Period 
Screening 
Treatment1 
End of 
treatment 
Extension 
Treatment 
15 
End of 
Extension 
16 
Follow-
up 17 
 
 
Unscheduled 
visit3 
 
 
Period 1 
Period 22 
Visit 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 12 
13 
E1, E2 
and E3 
 
 
Week 
≥- 4 to ≤-1 
0 
1 
2 
3 
4 
8 
12 16 24 
32 
40 48 
52 
56, 64 and 
72 
 
80 
maximum 
Visit window (days) 
±2 
 
±2 
±2 
±2 
±2 
±2 ±2 ±2 ±5 
±5 
±5 ±5 
±5 
±5 
±5 
±5 
ProSPI questionnaire  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
SaSPI questionnaire 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
DLQI questionnaire 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
PASI score 
X 12 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Please 
see 
details in 
Table 6-2 
X 
X 
 
SA-PASI score 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Pain, itching and scaling 
assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Optional BISF questionnaire 
 
X 
 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
Administration of 
investigational drug13 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X14 
 
 
 
 
Verification of patient drug 
administration log 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X3 
Primary endpoint 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Adverse events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
1 Patients discontinuing treatment prematurely during the treatment period should attend a visit for data collection (End of treatment visit) and should then enter the 
post-treatment follow-up period 
2 If the investigational drug is judged by the investigator and patient to be beneficial to the patient, the response to treatment will be considered to be favorable and monthly 
injections will continue to Week 48. In the absence of a favorable response at Week 16, the investigational drug will be discontinued and the patient should attend End of 
Treatment visit and will then enter the follow-up period. 
3 If judged necessary by the investigator 
4 Date of birth, gender, race, child-bearing potential 
5 Weight and vital signs at all visits and height only at Screening visit 
6 A repeat QuantiFERON® TB-Gold In-Tube test is recommended if the result of the first QuantiFERON® TB-Gold In-Tube test is ‘indeterminate’. The patient must be 


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Period 
Screening 
Treatment1 
End of 
treatment 
Extension 
Treatment 
15 
End of 
Extension 
16 
Follow-
up 17 
 
 
Unscheduled 
visit3 
 
 
Period 1 
Period 22 
Visit 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 12 
13 
E1, E2 
and E3 
 
 
Week 
≥- 4 to ≤-1 
0 
1 
2 
3 
4 
8 
12 16 24 
32 
40 48 
52 
56, 64 and 
72 
 
80 
maximum 
Visit window (days) 
±2 
 
±2 
±2 
±2 
±2 
±2 ±2 ±2 ±5 
±5 
±5 ±5 
±5 
±5 
±5 
±5 
referred for a follow-up tuberculosis workup (as per local guidelines) if either the first or the repeat test is ‘positive’ or if the results of both tests are ‘indeterminate’. If the first 
test is ‘indeterminate’, the investigator may decide not to repeat the test and to proceed directly to the workup, though this is not recommended. The patient will not be 
eligible for randomization if ‘active tuberculosis is present’ or if ‘latent tuberculosis is present’ and is untreated as per local guidelines 
7 Exclusion criterion: number 17 
8 Inclusion criterion: number 2 
9 For all women of child-bearing potential 
10 Fast plasma glucose, urea, creatinine, total bilirubin, alanine transaminase (ALT)/ glutamic pyruvate transaminase (SGPT), aspartate transaminase (AST)/glutamic 
oxaloacetic transaminase (SGOT), gamma glutamyl transpeptidase (GGT), alkaline phosphatase, sodium, chloride, potassium, bicarbonate, calcium, phosphorous, total 
protein, albumin and uric acid 
11 Complete blood count : hemoglobin, hematocrit, red blood cell count, white blood cell count with differential (neutrophils, bands neutrophils (optional), lymphocytes, 
monocytes, eosinophils, basophils) and platelet count12 Additionally patients will self-administer study treatment at home at weeks 20, 28, 36 and 44; these self-
administrations will be protocolled by the patient on the self-administration log, which will be brought to the site along with the PFS and outer box for compliance check  
12 PASI score at screening visit – V0 needs to be documented in medical source data. PASI scores at following visits (V1 to Follow-up visits) need to be entered into eCRF. 
13 The patient will be asked to self administer the injection at the investigation site when attending a site visit (Weeks 24, 32, 40 and 48) or at home between visits (Weeks 
20, 28, 36 and 44). If patient is not comfortable with self-injections, injections at home can be performed by a caregiver. 
14 Administration of investigational drug need to be done at the Visit 13 only if patient is entering  the extension treatment period. 
15 The assessments related to the extension treatment period are detailed in table 2 below. 
16 The End of Extension (EoE) visit should be performed 4 weeks after the last administration of study drug. 
17 The Follow-up (FU) visit should be performed 8 weeks after the last administration of study drug. 


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Table 6-2 
Assessment schedule during extension treatment period only 
 
 
 
 
 
Period 
Extension Treatment1 
Visit 
E1 
E2 
E3 
Week 
56 
64 
72 
Visit window (days) 
±5 
±5 
±5 
Physical examination2 
X 
X 
X 
Concomitant medication3 
X 
X 
X 
Urine Pregnancy test4 
X 
X 
X 
Administration of 
investigational drug5 
X 
X 
X 
Verification of patient drug 
administration log 
X 
X 
X 
Adverse events 
X 
X 
X 
1 Only for eligible patients who have received their injection of study drug at 
W48 before 3 January 2017 or before the commercialization of Cosentyx® in 
France, whichever occurs first. 
2  Weight and vital signs at all visits 
3 need to be entered into eCRF only if related to an AE 
4 For all women of child-bearing potential 
5 The patient will be asked to self administer the injection at home between 
visits (Weeks 52, 60 and 68). If patient is not comfortable with self-injections, 
injections at home can be performed by a caregiver. 


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6.2 
Patient demographics/other Screening characteristics 
 
At screening visit, patients must provide signed informed consent. Patient demographic and 
Baseline characteristics data will be collected (date of birth, gender, race), psoriasis medical 
history (date of first diagnosis for each form of psoriasis), previous psoriasis treatments 
(reason for discontinuation), relevant medical history, previous and concomitant medication, 
smoking history (current/previous, number of packets smoked per week), education level 
(none, primary education, secondary education, university).  
Rationale for collection of race. There are differences in the psoriasis expression in terms of 
severity and incidence, typically lower in Asian populations, in East Africa (Farber EM, Nall 
L. Epidemiology of Psoriasis. Roenig and psoriasis Maibach eds. 1998) and also in terms of 
clinical expression: in Asian populations, psoriasis may be associated with atopy. 
Furthermore, drugs metabolism and tolerance may vary depending on ethnicity and genetic 
characteristics (hepatic metabolism, HLA). Finally the registration agencies and particularly 
the FDA and the EMEA pay attention to the analysis of clinical response based on the race to 
be sure that the benefit-risk ratio is suitable for all ethnic groups. 
A physical examination will be performed (height, weight, vital signs), blood samples will be 
taken for hematology and biochemistry assessments and a pregnancy test will also be 
performed for all women of child-bearing potential. 
Inclusion and exclusion criteria must be checked at screening visit. PASI score must be ≥12, 
BSA ≥10 and IGA mod 2011 ≥3 at screening visit. 
 
6.2.1.1 
Standard 12-lead ECG 
 
A standard 12-lead ECG must be performed during the 12 weeks preceding study drug 
initiation. Interpretation of the tracing must be made by a qualified physician and clinically 
significant findings must be discussed with the Novartis Medical Monitor prior to enrolling 
the patient in the study. 
 
6.2.1.2 
QuantiFERON®-TB Gold In-Tube assay 
 
A QuantiFERON®-TB Gold In-Tube assay (QFT) will be performed locally at the Screening 
visit to screen all patients for latent tuberculosis infection in order to determine their eligibility 
for inclusion in the study. Any patient with a positive QTF result must not be included in the 
study. 
 
 
 


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6.2.1.3 
X-Ray 
 
An X-ray (or MRI, CT-scan) will be performed if results are not available during the 12 
weeks prior to the Screening visit. 
6.2.1.4 
Investigator’s Global Assessment (IGA mod 2011) 
 
The IGA mod 2011 will be conducted for overall psoriatic disease.  
 
Subjects require an IGA mod 2011 score at screening visit of 3 or 4 in order to participate in 
the study. The IGA mod 2011 rating scale for overall psoriatic disease is shown in Table 6-2. 
 
The IGA mod 2011 score will be recorded in the eCRF. 
 
Table 6-2 
The IGA mod 2011 rating scale 
            
Score 
Short  
 
Detailed description 
description 
 
0 
Clear 
 
No signs of psoriasis. Post-inflammatory hyperpigmentation   
may be present 
1 
Almost clear 
Normal to pink coloration of lesions; no thickening; no to 
minimal focal scaling 
2 
Mild 
  
  Pink to light red coloration; just detectable to mild thickening; 
 
 
predominantly fine scaling 
3 
Moderate 
Dull bright red, clearly distinguishable erythema; clearly 
distinguishable to moderate thickening; moderate scaling 
4 
Severe  
Bright to deep dark red coloration; severe thickening with 
hard edges; severe / coarse scaling covering almost all or all 
lesions 
Note: Involvement of nails is not part of the assessment 
 
6.2.1.5 
Assessment of total body surface area (BSA) 
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. 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 four percentages will be added up to estimate the total BSA affected by plaque-type 
psoriasis. 
 
 


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6.3 
Baseline characteristics, questionnaires and scores 
All Baseline assessments should be performed prior to the first study treatment administration 
at Visits 0 and 1. BSA and IGAmod2011 will be assessed at Visit 0 only, PASI at Visits 0 and 
1 and all questionnaires at Visit 1 only. Theses assessments were described in Table 6-1 in 
section 6. 
 
6.4 
Treatment exposure and compliance 
All injections of secukinumab 300 mg will be recorded by the investigator on the appropriate 
eCRF page. When injections are performed by the patient or caregiver at home (after 
Visit 8/Week 16), date and time of administration will be recorded in the patient drug 
administration log. Patients are required to return the used investigational medication kit 
(PFSs and packaging) and the patient administration log at each visit to the investigational site 
in order for the investigator to monitor compliance. 
The investigator should emphasize the importance of compliance for patient safety and study 
validity.  The patient should be instructed to attend the study visits as scheduled and to take 
the investigational drug exactly as prescribed. The patient should be informed to contact the 
investigator if he/she is unable, for any reason, to attend a study visit as scheduled or to 
administer the investigational drug at home as prescribed. 
 
6.5 
Efficacy 
The efficacy assessments listed in Table 6-1 will be performed the specified visits during the 
treatment period (before each administration of the investigational drug), at each 
post-treatment follow-up visit. Psoriasis symptoms will be assessed using the following 
questionnaires: DLQI, SPI, PASI and PSD (pain, itching and scaling assessment). 
Completed questionnaires will be reviewed and examined by the investigator before the 
clinical examination for responses which 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 patient. 
If the occurrence of AEs or SAEs is confirmed, the physician must record the events as per 
instructions given in Section 7 of the protocol. Investigators should not encourage patients to 
change the responses reported in the various Patient-Reported Outcome (PRO) questionnaires. 
6.5.1 
Psoriasis questionnaires and scores 
 
Psoriasis questionnaires and scores should be completed in the following order:  
• About scores: 1/pro-SPI,  2/IGA and 3/ PASI 
• About questionnaires: 4/saSPI , 5/DLQI, 6/PSD, 7/SA-PASI and 8/optional BISF 
questionnaires (described in section 6.7). 
 


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6.5.1.1 
SPI questionnaire 
The SPI questionnaire is a new tool developed to provide a concise but holistic summary of 
psoriasis assessment. The questionnaire consists of 2 complementary versions: one to be 
completed by the investigator (proSPI) and one by the patient (saSPI). Each version comprises 
3 components: current extent and severity of psoriasis plaques (s), psychosocial impact (p), 
and historical course of disease and intervention (i).  
Psoriasis extent and severity (s): part 1 
This score is weighted to reflect functional or psychosocial impact of psoriasis, with extra 
weight given to the scalp, face, hands, feet and anogenital skin. It consists of 2 components:  
• Extent of plaques (part 1A): psoriasis plaques visible at 10 unequal critical 
localizations, each on a 3-point scale:  0=absent or minimal, 0.5=‘noticeable’ or 
1=extensive (finger nails are scored with hands and toenails with feet). 
• Plaque severity (part 1B): each of the 10 critical locations are scored on a scale of 0 
(essentially clear) to 5 (intensely inflamed skin).  
The scores for the 2 components, psoriasis plaque extent and severity, are multiplied together 
to give a maximum score of 50. 
Psychosocial impact (p): part 2  
Assessed on a VAS of 0 (psoriasis having no effect on patient) to 10 (psoriasis affecting 
patient very much). 
Historical course and intervention (i): part 3 
Assessed by means of 10 questions: 4 questions related to disease course and 6 questions 
about previous interventions (for each question, ticked=1 point) (Chularojanamontri et al., J 
Inv Dermatol 2013).  
The SPI questionnaire is included in Appendix 1. 
6.5.1.2 
PASI score 
The PASI score will be used to assess the severity of psoriasis lesions. Various regions of the 
body: head (including neck: H), upper limbs (U), trunk (including axillae and groin: T) and 
lower limbs (including buttocks: L) are assessed and lesion surface area is measured. In this 
questionnaire, the symptoms erythema (E), thickening (plaque elevation, induration: I) and 
scaling (desquamation: D), are assessed for each body region individually on a scale of 0 
(none) to 4 (very severe).  
Taking into account that the head, upper limbs, trunk and lower limbs can be estimated as 
corresponding to approximately 10%, 20%, 30% and 40% of body surface area, respectively, 
the total PASI score can be 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, 
Where A = area score based on true area (%) ranging from 0 (no involvement) to 6 (90%-
100%). The total score therefore ranges from 0 (no psoriasis sign) to a theoretical maximum 
of 72.0. 


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The PASI scoring system is decribed in Table 6-3 and PASI score is included in Appendix 2 
(Fredriksson T and Pettersson U Dermatologica 1978, Weisman S, Pollack CR and Gottschalk 
RWJ Dermatolog Treat 2003, Gottlieb AB, Griffiths CEM et al. Br J Dermatol 2005). 
 
Table 6-3 
The PASI scoring system 
 
 
 
Definitions of efficacy variables based on PASI 
The following definitions will be used in this study based on the CHMP guidelines for 
psoriasis (CHMP/EWP/2454/02 2004): 
• PASI 50 responders (partial response): patients achieving ≥ 50% improvement 
(reduction) in PASI score compared to Baseline. 


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• PASI 75 responders: patients achieving ≥ 75% improvement (reduction) in PASI 
score, compared to Baseline. 
• PASI 90 responders: patients achieving ≥ 90% improvement (reduction) in PASI 
score, compared to Baseline. 
• PASI 100 responders: no psoriasis / remission (PASI=0). 
6.5.1.3 
SA-PASI score 
The SA-PASI score is a PASI-like structured patient self-administered instrument to assess 
psoriasis severity of the same regions assessed using the PASI score (Section 6.5.1.2). Disease 
severity is assessed by the patient using 3 modified 120 mm VASs evaluating erythema (on a 
scale of no redness to dark red), induration (no thickness to very thick) and scaliness (no scale 
to very flaky). 
To estimate the surface area involved, a line-drawing silhouhette of the front and back of a 
body is presented to patients who shade in the areas currently affected by psoriasis. A single 
investigator who had not evaluated the patient assigns a numeric value of 0 to 6 based on the 
silhouette shading and corresponding to 0 to 100% involvement for ech of the following four 
areas: head, upper extremities, trunk, and lower extremities (Fleischer et al. J Inv Dermatol 
1994, Feldman SR et al. J Inv Dermatol 1996). 
The total SAPASI score can be calculated using the following formula: 
SAPASI = [(0.1xAH) + (0.2xAU) + (0.3xAT) + (0.4xAL)] / [0.0333 x (VASE + VASI + VASS)] 
The SA-PASI score is presented in Appendix 3.  
6.5.1.4 
Pain, itching and scaling assessment (PSD questionnaire) 
A PSD questionnaire completed by the patient will be used to evaluate 3 psoriasis symptoms, 
pain, itching and scaling, each on a scale of 0 (none) to 10 (worst possible).  
The PSD questionnaire is included in Appendix 5. 
 
6.5.2 
DLQI questionnaire 
The DLQI questionnaire consists of a series of questions related to symptoms and feelings, 
daily activities, leisure, work and school, personal relationships and treatment scored on a 
scale of 0 (not answered, not relevant, not at all) to 3 (very much or prevented work or 
studying in the case of question 7). The total DLQI ranges from 0 (minimum) to 30 points 
(maximum). If the score is 0 or 1, psoriasis is considered as having no effect at all on the 
patient’s life, a score of 2 to 5 indicates a small effect, 6 to 10 indicates a moderate effect, 11 
to 20 a very large effect and 21 to 30 indicates an extremely large effect on patient’s life. 
(Finley and Khan Clin Experi Dermato 1994).  
Each subscale of the DLQI may also be analyzed separately.  
The DLQI questionnaire is included in Appendix 4. 


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6.5.3 
Appropriateness of efficacy assessments 
DLQI is a validated questionnaire for evaluating the impact of dermatological diseases on 
patient QoL. The PASI questionnaire is specific for assessing the area and severity of the 
signs 
of 
psoriasis. 
PASI 
is 
considered 
acceptable 
by 
the 
health 
authorities 
(CHMP/EWP/2454/02 2004) to assess treatment efficacy in combination with the DLQI. The 
use of questionnaires for the evaluation of the intensity of pain, itching and scaling is a 
standard method used in clinical studies.   
The SPI is a newly developed tool providing a concise but holistic summary of psoriasis 
assessment. It has several advantages over current tools:  1) it evaluates specifically several 
critical localizations (scalp, face, hands, feet, anogenital skin); 2) it can be assessed by both 
the physician (proSPI component) and the patient (saSPI); and 3) it assesses psychological 
impact and includes historical features. 
The efficacy and safety of secukinumab AIN457 have been studied in pivotal Phase III 
clinical trials employing the PASI and DLQI questionnaires. 
6.6 
Safety 
At each visit, a physical examination should be performed and vital signs must be measured, 
preferably by the same person at each visit. In addition, any AE must be reported; blood 
samples will be taken for hematology and biochemistry assessments at inclusion and End of 
treatment visits (plus unscheduled visits if deemed appropriate). A pregnancy test will be 
performed for all women of child-bearing potential (Table 6-1). 
6.6.1 
Physical examination 
A physical examination should include the examination of general appearance, skin, neck 
(including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, 
extremities, vascular and neurological. The investigator can perform other examinations if 
deemed necessary based on patient’s previous medical history.  
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings that are present prior to signing informed consent must be 
included in the Medical History part of the eCRF. Significant findings made after signing the 
informed consent which meet the definition of an AE must be recorded on the Adverse Event 
section of the eCRF. 
6.6.2 
Vital signs 
Vital signs (including blood pressure and pulse measurements) will be determined after the 
patient has been sitting for five minutes, with back supported and both feet placed on the 
floor. Systolic and diastolic blood pressure will be measured using a validated device with an 
appropriately sized cuff. Two sitting measurements will be made at 1-2 minute intervals and 
the mean of the two measurements will be used. If a sufficiently large cuff is unavailable, a 
sphygmomanometer with an appropriately sized cuff may be used. Normal values for vital 
signs are presented in Appendix 5. 


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6.6.3 
Height and weight 
Height in centimeters (cm) will be measured only at the Screening visit. Body weight (to the 
nearest 0.1 kilogram (kg) in indoor clothing, but without shoes) will be measured at each visit, 
preferably using the same weighing scales throughout the study. 
6.6.4 
Laboratory evaluations 
Collected samples will be analyzed locally. 
Clinically notable laboratory findings are defined in Appendix 9. 
6.6.4.1 
Hematology 
Hemoglobin, hematocrit, red blood cell (RBC) count, white blood cell (WBC) count with 
differential (neutrophils,  bands neutrophils (optional), lymphocytes, monocytes, eosinophils, 
basophils) and platelet counts will be measured at screening visit, first visit  (Week 0) and at 
End of treatment visit  (Week 52). 
6.6.4.2 
Biochemistry 
Fast plasma glucose, urea, creatinine, total bilirubin, alanine transaminase (ALT)/ glutamic 
pyruvate transaminase (SGPT), aspartate transaminase (AST)/glutamic oxaloacetic 
transaminase (SGOT), gamma glutamyl transpeptidase (GGT), alkaline phosphatase, sodium, 
chloride, potassium, bicarbonate, calcium, phosphorous, total protein, albumin and uric acid 
will be measured at screening visit, first visit (Week 0) and at End of treatment visit  (Week 
52). 
6.6.5 
Pregnancy and assessments of fertility 
A serum β-hCG test will be performed for all women of child-bearing potential at the 
Screening visit. A woman with a confirmed positive pregnancy test at Screening is not 
eligible for participation in the study. A urine pregnancy test will be performed at all other 
visits (Table 6-1). A positive urine pregnancy test during the treatment period of the study 
requires immediate interruption of study treatment until serum β-hCG is performed and found 
to be negative. If the serum β-hCG test is positive, study treatment must be definitively 
discontinued, as described in Section 5.5.10. An effective contraception method must be used 
by all women of child-bearing potential during the study. At each study visit, the 
investigator/qualified site staff will review with the female patients of child-bearing potential 
requirements for appropriate contraception while participating in the study. 
6.6.6 
Appropriateness of safety measurements 
The safety assessments to be performed during the study are reliable and are standard for the 
use of a biologic immunomodulating agent in the treatment of psoriasis.  


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6.7 
Other assessments 
6.7.1 
Sexual function 
Data related to sexual dysfunction will be collected only for patients willing to complete 
sexual function questionnaire.  The BISF-w/m will be used to assess sexual dysfunction. 
The BISF-m is a brief patient self-reported questionnaire (22 items) related to sexual 
functioning.  It was developed for the specific purpose of assessing key domains of sexual 
functioning in men (e.g. sexual interest, activity, satisfaction and preference). 
The BISF-w is an adaptation of the men’s questionnaire specifically for women (22 items). 
The key domains are sexual thoughts/desire, arousal, activity, pleasure/orgasm, satisfaction, 
problems affecting sexual function. 
BISF-m and BISF-w questionnaires are presented in Appendix 6 and 7, respectively. 
7 
Safety monitoring 
7.1 
Adverse events 
An AE is any untoward medical occurrence (i.e. any undesirable sign, abnormal laboratory 
findings, symptom or medical condition) in a patient after providing signed informed consent 
for participation in the study. Therefore, an AE may or may not be temporally or causally 
related to the use of the investigational drug. 
The occurrence of AEs should be sought by non-directive questioning of the patient at each 
visit during the study. AEs may also be detected when they are volunteered by the patient 
during or between visits or through physical examination, laboratory test, or other 
assessments. 
Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
following criteria: 
• They induce clinical signs or symptoms.  
• They are considered clinically significant.  
• They require therapy.  
Clinically significant abnormal laboratory values or test results should be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
Baseline or the previous visit, or values which are considered to be non-typical in a patient 
with underlying disease. Investigators have the responsibility for managing the safety of 
individual patient and identifying AEs. Alert ranges for labs and other test abnormalities are 
included in Appendix 6. 
Information concerning all AEs will be collected and recorded on an Adverse Event Case 
Report Form and will be followed-up as appropriate.  
Medical conditions/diseases present before starting investigational drug will only be 
considered as AEs if they worsen after starting the investigational drug.  


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Where possible, each AE should be described by: 
• Severity grade:  
o 
Mild: usually transient in nature and generally not interfering with normal 
activities. 
o 
Moderate: sufficiently discomforting to interfere with normal activities. 
o 
Severe: prevents normal activities. 
• Relationship to the investigational drug.  
• Duration (start and end dates), or whether the event is ongoing at the final visit. 
• Whether it constitutes a SAE. 
• Action taken regarding investigational treatment.  
• Whether 
other 
medication 
or 
therapies 
have 
been 
taken 
(concomitant 
medication/non-drug therapy). 
• Outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown). 
 
Once an AE is detected, it should be followed until its resolution or until it is judged to be 
permanent, and assessment should be made at each visit (or more frequently, if necessary) of 
any changes in severity, the suspected relationship to the study drug, the interventions 
required to treat it, and the outcome. 
Information about common side effects already known about the investigational drug can be 
found in the Cosentyx Summary of Product Characteristics. This information will be included 
in the patient informed consent and should be discussed with the patient during the study as 
needed. 
The investigator should also instruct each patient to report any new AE (beyond the protocol 
observation period) that the patient, or the patient’s personal physician, believes might 
reasonably be related to study treatment. This information should be recorded in the 
investigator’s source documents; however, if the AE meets the criteria of a SAE, it must be 
reported to Novartis. 
7.2 
Serious Adverse Events  
 A SAE is any AE (appearance of (or worsening of any pre-existing) undesirable sign, 
symptom or medical condition 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:  
o Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition.  


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o Elective or pre-planned treatment for a pre-existing condition unrelated to the 
indication under study that has not worsened since the start of the investigational 
drug. 
o Social reasons and respite care in the absence of any deterioration in the patient’s 
general condition.  
• Is medically significant, i.e. defined as an event that jeopardizes the patient or may 
require medical or surgical intervention to prevent one of the outcomes listed above 
(e.g. may require 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).  
• Transmission of an infectious agent via the investigational drug.  
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 patient 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 more severe. 
As far as possible, each SAE will also be described by (but not limited to):  
• Duration (onset date = date of first signs or symptoms, and end date).  
• Severity (mild, moderate, severe).  
• Relationship to current investigational drug (suspected / not suspected as judged by the 
investigator). 
• Action(s) taken and investigation results, if applicable.  
• Concomitant medication details.  
• Outcome. 
Unlike routine safety assessments, SAEs are monitored continuously and have special 
reporting requirements; see Section 7.3. 
7.3 
Serious Adverse Event reporting 
7.3.1 
Notification of an SAE to Novartis Pharmaceuticals Drug Safety & 
Epidemiology (DS&E) Department  
Information related to all SAEs must be collected and recorded on the Serious Adverse Event 
Report Form and be reported by the investigator to Novartis DS&E Department within 
24 hours of knowledge, even if it is not thought to be treatment-related. Follow-up 
information about a previously reported SAE will also be reported to Novartis DS&E 
Department within 24 hours of receipt. Recurrent episodes, complications, or progression of 
the initial SAE must be reported as follow-up to the original episode, regardless of when the 
event occurs. This report must be submitted within 24 hours of the investigator receiving the 
follow-up information. An SAE that is considered completely unrelated to a previously 
reported one should be reported separately as a new event. 
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent and until 60 days following the last administration of 


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investigational drug (i.e. last follow-up visit, 8 weeks after last investigational drug 
administration) must be reported to Novartis within 24 hours of knowledge. Any SAEs 
experienced after the 60 days period should only be reported to Novartis if the investigator 
suspects a causal relationship to study treatment.  
If the SAE is not previously documented in the Cosentyx Summary of Product Characteristics 
and is thought to be related to the investigational treatment a DS&E Department associate 
may urgently require further information from the investigator for Health Authority reporting. 
Novartis may need to issue an IN to inform all investigators involved in any study with the 
same investigational treatment that this SAE has been reported. Suspected Unexpected 
Serious Adverse Reactions will be collected and reported to the competent authorities and 
relevant ethics committees in accordance with EU Guidance 2011/C 172/01 or as per national 
regulatory requirements in participating countries. 
7.3.2 
Reporting procedure for an SAE  
The investigator must complete the SAE Report Form in English, assess the relationship to 
study treatment and send the completed and signed form by fax within 24 hours to 
Novartis DS&E Department 
. The 
original and the duplicate copies of the SAE Form sheet will be kept at the study site. Should 
the investigator realize that the number of pages received by Novartis DS&E Department 
doesn’t match the number of pages faxed by the investigator, the SAE form should be 
re-faxed entirely to Novartis DS&E Department.  
Follow-up information will be sent to the same person to whom the original SAE Form was 
sent, re-stating the date of the original report. A new SAE Form will be used (stating that this 
is a ‘follow-up’). The follow-up report should describe whether the event has resolved or is 
continuing, if and how the event was treated, and whether the patient continued or 
discontinued study participation. The form and fax confirmation sheet will be retained by the 
study site.  
7.4 
Pregnancy reporting 
To ensure patient safety, each pregnancy in a patient will be reported to Novartis within 
24 hours of knowledge. Pregnancy will be recorded on a Clinical Trial Pregnancy Form and 
reported by the investigator to the local Novartis DS&E Department.   
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 follow-up will be 
recorded on the same form and will include an assessment of the possible relationship to the 
Novartis investigational drug of any pregnancy outcome.  
Any SAE experienced during pregnancy will be reported on the SAE Report Form.  
Pregnancy outcomes must be collected for the female partners of any males who took 
investigational drug in this study. Consent to report information regarding these pregnancy 
outcomes should be obtained from the female partner. 
 


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8 
Data review and database management 
8.1 
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and eCRFs with the investigators and their staff. 
During the study, the field monitor will visit the site regularly to check the completeness of 
patient records, the accuracy of entries in the eCRFs, the adherence to the protocol and to 
Good Clinical Practice, the progress of enrollment, and to ensure that investigational drug is 
being stored, dispensed, and accounted for according to specifications. Key study personnel 
must be available to assist the field monitor during these visits. 
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information in eCRFs must be traceable to these source documents in the 
patient's file. The investigator must also keep the original informed consent form signed by 
the patient (a signed copy must be given to the patient). 
The investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the eCRF entries. Novartis monitoring standards require full 
verification for the presence of signed informed consent, adherence to the inclusion/exclusion 
criteria, documentation of SAEs, and of data that will be used for the primary variable. 
Additional checks of the consistency of the source data with the eCRFs will be performed 
according to the study-specific monitoring plan. No information in source documents related 
to the identity of the patients will be disclosed. 
8.2 
Data collection 
Designated investigator staff will enter the data required by the protocol into the eCRFs using 
fully validated software conforming to 21 CFR Part 11 requirements. Designated investigator 
site staff will not be given access to the EDC system until they have been trained. Automatic 
validation programs will check for data discrepancies and, by generating appropriate error 
messages, allow the data to be confirmed or corrected before transfer of the data to the CRO 
working on behalf of Novartis. The Investigator must certify that the data entered into the 
eCRFs are complete and accurate. After database lock, the investigator will receive copies of 
the patient data for archiving at the investigational site.  
8.3 
Database management and quality control 
The CRO working on behalf of Novartis will review the data entered into the CRFs by 
investigational staff for completeness and accuracy and instruct the site personnel to make any 
required corrections or additions. Queries will be sent to the investigational site using an 
electronic data query. Designated investigator site staff will be required to respond to the 
query and confirm or correct the data. If an electronic query system is not used, a paper Data 
Query Form will be faxed to the site. Site personnel will complete and sign the faxed copy 
and fax it back to Novartis staff that will make the correction to the database. The signed copy 
of the Data Query Form is kept at the investigator site. 


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Concomitant medications entered into the database will be coded using the World Health 
Organization (WHO) Drug Reference List, which employs the Anatomical Therapeutic 
Chemical (ATC) classification system. Concomitant procedures, non-drug therapies and AEs 
will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) terminology. 
All laboratory samples will be processed locally and the results will be entered on study eCRF 
by sites staff.  
Patients will be provided with the PRO questionnaires on paper to be completed at each visit 
before injection of the investigational drug.  
All completed questionnaires will be collected and checked for completion by the investigator or 
delegated staff and then a copy will be sent to the CRO working on behalf of Novartis.  
Answers provided by the patients to the saSPI, SA-PASI, DLQI, PSD, and BISF questionnaires 
(if available) will be transferred exactly as completed (without any modification or interpretation) 
by the CRO working on behalf of Novartis on the appropriate screens of the eCRF. Original 
questionnaires will be filed as source documents on site. 
At the study conclusion, 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. Any changes to the database after that time can only be made 
after written agreement by Novartis Development management. 
8.4 
Data Monitoring Committee 
Not required. 
8.5 
Adjudication Committee 
Not required. 
9 
Data analysis 
The Statistical Analysis Plan (SAP) will be written by the CRO in charge of the study and will 
be validated by Novartis prior to performing the analysis. 
All analyses will be performed by the CRO in charge of the study and will be validated by 
Novartis. 
Quantitative variables will be presented in terms of mean, standard deviation, median and 
extreme values, and in terms of absolute frequency and percentage by modality for qualitative 
variables. If appropriate, 95% Confidence Intervals (CIs) will be presented. 
For statistical analysis, Baseline will be defined as the last available non-missing value 
collected just prior to the start of treatment. Patients with Screening assessments but not 
included in the study will only be listed. 
Unless otherwise specified, all statistical tests will be two-sided and will use the 0.05 level of 
significance. 
All extension period data will be presented separately from the treatment period and will be 
outlined in more detail in the SAP.  


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Analyses will be performed using SAS® software version 9.2 or higher. 
Further technical details and discussions of the following statistical considerations will be 
provided in the SAP. 
9.1 
Analysis sets 
The following analysis sets will be used in this study: 
Included Set (IS): The included set will comprise all patients included in the study.  
Full Analysis Set (FAS): The FAS will comprise all patients from the IS administered at least 
one dose of investigational drug during the treatment period with at least one Baseline and 
one post-Baseline SPI evaluation.  
Safety Analysis Set (SAF): The SAF will comprise all patients administered at least one dose 
of investigational drug during the treatment period.  
Per Protocol Set (PPS): The PPS will comprise all patients administered at least one dose of 
investigational drug during the treatment period without any major protocol deviation. 
All analyses will be based on the FAS population, unless otherwise specified.  
9.2 
Patient demographics and other Baseline characteristics 
Descriptive statistics will be provided for patient demographics and baseline characteristics 
(including the Baseline values of the main efficacy endpoints) on the IS population.  
9.3 
Medical history 
Any condition entered as medical history or current medical condition at the Screening visit 
will be coded using the MedDRA dictionary and will be summarized by System Organ Class 
(SOC) and Preferred Term (PT). Summaries for psoriasis-specific medical history will also be 
presented. 
9.4 
Treatments 
9.4.1 
Investigational drug 
The analysis of data related to investigational drug administration will be performed on the 
SAF. The duration of exposure to investigational drug will be summarized.  
9.4.2 
Prior and concomitant treatment 
Previous and concomitant medications will be summarized in separate tables.  
A previous medication is defined as a treatment taken but stopped prior to first administration 
of investigational drug. Any medication administered at least once between the day of first 
injection of investigational drug and the last day of study visit will be considered as a 
concomitant medication, including a medication initiated pre-screening and ongoing at the 
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Medications will be presented in alphabetical order, by Anatomical Therapeutic Classification 
(ATC) codes and grouped by anatomical main group. Tables will also show the overall 
number and percentage of patients receiving at least one treatment of a particular ATC code 
and at least one treatment in a particular anatomical main group.  
In addition, medical procedures and significant non-drug therapies will be summarized as 
coded in MedDRA. 
9.5 
Analysis of the primary and key secondary variable(s) 
9.5.1 
Variable(s) 
The primary variables for this study are the changes from Baseline of proSPI (s) and saSPI (s) 
at Week 16. 
The primary analysis of this study will be performed on the FAS population at Week 16 
compared to Baseline and will be:  
• To evaluate the change from baseline of proSPI (s). 
• To evaluate the change from baseline of saSPI (s). 
The key secondary variable for this study is the PASI score. The key secondary analysis will 
be to assess PASI and to evaluate the correlation between PASI and proSPI (s) in the FAS. 
9.5.2 
Statistical model, hypothesis, and method of analysis 
Summary statistics will be presented for changes from Baseline to Week 16 (proSPI (s), saSPI 
(s)) for all patients in the FAS. Associated 95% CIs will be presented. 
To assess the primary objective, the proSPI (s) and saSPI (s) will be analyzed using a paired t-
test (baseline vs Week 16). The null hypothesis tested in this model is that there is no 
difference between means at baseline and Week 16.  
As there are co-primary endpoints an adjustment for multiplicity will be performed using the 
Hochberg procedure and the family-wise type-I-error will be set to α=5% (2-sided). The 
Hochberg procedure was chosen as the most powerful adjustment due to the positive 
association between proSPI (s) and saSPI (s) (L Chularojanamontri et al., 2013).  
The Hochberg procedure will be applied as follows, if the maximum of the two p-values is 
rejected at the 5% level (2-sided) then both hypotheses are rejected and statistical significance 
is claimed for both endpoints. Otherwise if the maximum of the 2 p-values is not rejected, 
then the minimum p-value is tested at the 2.5% level (2-sided), if rejected then statistical 
significance is claimed just for this endpoint. 
In the event the data is non-normal the Wilcoxon signed rank test will be performed. 
Evolution of PASI score and PASI response during the study will be described and associated 
95% CIs will be presented. Change from baseline to Week 16 of the PASI score will be 
analyzed as for the primary analysis. 
Spearman’s correlation coefficient and the associated test will be used to evaluate the 
correlation between PASI and proSPI (s) at all weeks. 


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9.5.3 
Handling of missing values/censoring/discontinuations 
For the analysis of the primary endpoint in the FAS population and in case of unavailable 
assessment at Week 16, a LOCF (Last Observation Carried Forward) approach will be used. 
This approach will consist of replacing the missing Week 16 assessment by the value of the 
last available primary endpoint assessment. A sensitivity analysis will be conducted by 
performing two analyses, one using the LOCF completion approach and the other based only 
on the available data (no missing data replacement). Missing values for all secondary 
endpoints or other outcomes (e.g. safety or laboratory measurements) will not be replaced. 
9.5.4 
Supportive analyses 
The same analysis will be performed on the PPS population. 
Subgroups of interest defined by the scientific committee will be investigated also if required 
(e.g. psoriasis duration at baseline, baseline bodyweight …) and will be detailed in the SAP 
before the database lock. 
9.6 
Analysis of secondary variables 
9.6.1 
Efficacy variables 
Simplified Psoriasis Index 
Absolute values and change from baseline (at all assessment periods) for each SPI component 
will be described and analyzed as for the primary efficacy analysis.  
ProSPI (s) and saSPI (s) will be analyzed using a paired t-test at week 16. Descriptive 
statistics will be presented for each component at each time point. 
Dermatology Life Quality Index 
The DLQI contains six functional scales (i.e. symptoms and feeling, daily activities, leisure, 
work and school, personal relationships, treatment). 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. 
Self-administered PASI 
Absolute values and change from baseline of the sa-PASI (at all assessment periods) will be 
described. 
Psoriasis Symptom Diary 
For PSD, descriptive summary statistics will be presented for absolute values and change 
from baseline by visit for intensity of pain, itching and scaling. 


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Correlations between scores 
Relationships between scores will be explored using Spearman’s correlation coefficient and 
the associated test. 
Appropriate statistical tests performed on these secondary efficacy variables will be detailed 
in the SAP. 
9.6.2 
Safety variables 
All safety evaluations will be performed on the SAF. 
9.6.2.1 
Adverse Events 
Treatment-emergent adverse events (TEAEs: events starting after the first dose of 
investigational drug or events present prior to the first dose of investigational drug but with 
increased severity) will be summarized by PT.  
AEs will be summarized by presenting the number and percentage of patients with: 
• 
An AE. 
• 
An AE by primary SOC. 
• 
An AE by PT. 
Summaries will also be presented for AEs by severity and for investigational drug related 
AEs. If a patient reports more than one AE with the same PT, only the greatest severity will 
be presented for this AE. If a patient reports more than one AE within the same primary SOC, 
the patient will be counted only once with the highest severity at the SOC level, where 
applicable. 
All other information collected will be tabulated and listed as appropriate. 
Separate summaries will be provided for any death, SAE, any other significant AE leading to 
investigational drug discontinuation.  
These summaries will be presented for the whole study period.  
9.6.2.2 
Laboratory data 
The summary of the data for laboratory evaluations will be presented for both types of 
laboratory tests (hematology and biochemistry). Descriptive summary statistics for the 
absolute values and changes from Baseline at each study visit will be presented. 
Descriptive summaries will be presented by type and by laboratory test. Changes from 
Baseline will only be summarized for patients with both Baseline and post-Baseline 
assessments. 
For each parameter, the maximum change from Baseline within each study period will be 
analyzed. In addition, shift tables will be produced for all parameters in order to compare 
patient Baseline laboratory evaluation with the observed value at each visit. For these shift 
tables, the normal laboratory ranges will be used to evaluate whether a particular laboratory 
test value is normal, low, or high at each visit relative to whether or not the Baseline value 


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was normal, low, or high. These summaries will be presented by laboratory test. Shifts will be 
presented by visit as well as post-Baseline for the most extreme values. 
9.6.2.3 
Vital signs 
Analysis of the vital sign measurements using summary statistics for the absolute values and 
changes from Baseline at each post-Baseline visit will be performed. These descriptive 
summaries will be presented by vital sign. Change from Baseline will be summarized only for 
patients with both Baseline and post-Baseline values. All information collected will be listed 
by patient, by visit, and abnormal values will be flagged. 
9.6.3 
Resource utilization 
Data relating to resource utilization will not be analyzed in this study. 
9.6.4 
Health-related Quality of Life 
QoL is a secondary endpoint (DLQI) and as such is described in Section 9.6.1. 
9.6.5 
Pharmacokinetics 
Not applicable. 
9.6.6 
Pharmacogenetics/pharmacogenomics 
Not applicable. 
9.6.7 
Biomarkers 
Not applicable. 
9.6.8 
PK/PD 
Not applicable. 
9.7 
Exploratory analyses 
Correlations between scores 
Correlations between saSPI and DLQI, between saSPI (s) and PASI, and between proSPI and 
saSPI (component s and p) will be evaluated using the Spearman correlation coefficient. The 
associated p-value will be presented. 
Sexual dysfunction 
To explore sexual dysfunction (only in patients willing to complete sexual function 
questionnaire), descriptive summary statistics will be presented for absolute values and 
change from baseline of BISF-m and BISF-w scores. 
Sexual dysfunction analysis will be performed if a sufficient number of patients agreed to 
participate. 
Responsiveness to change 


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An analysis of the SPI responsiveness to change will be led in order to investigate if 
reductions in psoriasis severity resulting from treatment would be accompanied by 
corresponding reductions in proSPI–s and saSPI–s scores. This analysis will be performed by 
the calculation of receiver operating characteristic (ROC) area under the curve (AUC). Three 
criteria of response will be examined to evaluate each score: ≥75, ≥90, and 100% reduction in 
PASI score. 
9.8 
Interim analyses 
No interim analysis is planned in this study. 
9.9 
Sample size calculation 
All sample size calculations were performed using EAST 6.0. 
The primary objective of this study is to evaluate the benefit of secukinumab on the severity 
and psychosocial burden of psoriasis based on SPI change at Week 16 compared to Baseline 
in patients suffering from moderate to severe plaque psoriasis. 
The sample size calculation is based upon the SPI variable which is the primary endpoint. 
A similar study by Chularojanamontri et al. J Inv dermatol 2013 showed that it is possible to 
detect responsiveness and a minimum clinically important difference (an absolute change of 5 
and 7 for proSPI (s) and saSPI (s), respectively) derived from PASI changes with n=100 
patients. The study showed a standard deviation at week 10 in change from baseline of 7.35 in 
proSPI (s) and 10.35 in saSPI (S) as the standard deviation at week 16 is expected to be 
higher, conservative standard deviation estimates of 14 and 19 will be assumed for change at 
week 16 for proSPI (s) and saSPI (s) respectively. 
Based on an analysis of paired differences, in order to have at least  90% power to detect a 
significant clinical difference for each index at the 2.5% level (2-sided), it can be estimated 
that a sample size of 100 evaluable patients would be sufficient. 
Taking into account an anticipated drop-out of 20 patients, 120 patients will need to be 
included in the study. 
10 
Ethical considerations 
10.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented and reported in accordance with 
the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local 
regulations (European Directive 2001/20/EC), and with the ethical principles laid down in the 
Declaration of Helsinki. 
10.2 
Informed consent procedures 
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent, or, if incapable of doing 
so, after such consent has been provided by a legally acceptable representative of the patient. 


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In cases where the patient’s representative gives consent, the patient should be informed about 
the study to the extent possible given his/her understanding. If the patient is capable of doing 
so, he/she should indicate assent by personally signing and dating the written informed 
consent document or a separate assent form. Informed consent must be obtained before 
conducting any study-specific procedure (i.e. all of the procedures described in the protocol). 
The process of obtaining informed consent should be documented in the patient source 
documents.  
Novartis will provide to investigators in a separate document a proposed ICF that complies 
with the ICH GCP guideline and regulatory requirements and is considered appropriate for 
this study. Any changes to the proposed consent form suggested by the investigator must be 
agreed to by Novartis before submission to the IRB/IEC, and a copy of the approved version 
must be provided to the Novartis monitor after IRB/IEC approval. 
Women of child-bearing potential should be informed that taking the investigational drug may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that 
in order to participate in the study they must adhere to the contraception requirement for the 
duration of the study. If there is any question that the patient will not reliably comply, they 
should not be entered in the study. 
10.3 
Responsibilities of the investigator and IRB/IEC 
The protocol and the proposed ICF must be reviewed and approved by a properly constituted 
IRB/IEC before the start of the study. A signed and dated statement that the protocol and 
informed consent have been approved by the IRB/IEC must be given to Novartis before study 
initiation. Prior to the start of the study, the investigator is required to sign a protocol 
signature page confirming his/her agreement to conduct the study in accordance with these 
documents and all of the instructions and procedures found in this protocol and to give access 
to all relevant data and records to Novartis monitors, auditors, Novartis Clinical Quality 
Assurance representatives, designated agents of Novartis, IRBs/IECs, and regulatory 
authorities as required. If an inspection of the clinical site is requested by a regulatory 
authority, the investigator must inform Novartis immediately that this request has been made. 
10.4 
Publication of study protocol and results 
Novartis assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov. In addition, upon study completion and 
finalization of the study report the results of this trial will be either submitted for publication 
and/or posted in a publicly accessible database of clinical trial results. 
11 
Protocol adherence 
Investigators ascertain they will apply due diligence to avoid protocol deviations. Under no 
circumstances should the investigator contact Novartis or its agents, if any, monitoring the 
trial to request approval of a protocol deviation, as requests to approve deviations will not be 
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This protocol defines the study objectives, the study procedures and the data to be collected 
on study participants.  Under no circumstance should an investigator collect additional data or 
conduct any additional procedure for any research related purpose involving any 
investigational drugs.  
If the investigator feels a protocol deviation would improve the conduct of the study this must 
be considered as a protocol amendment, and unless such an amendment is agreed upon by 
Novartis and approved by the IRB/IEC it cannot be implemented. All significant protocol 
deviations will be recorded and reported in the CSR. 
11.1 
Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, Health Authorities where required, and the IRB/IEC. Only 
amendments that are required for patient safety may be implemented prior to IRB/IEC 
approval. Notwithstanding the need for approval of formal protocol amendments, the 
investigator is expected to take any immediate action required for the safety of any patient 
included in this study, even if this action represents a deviation from the protocol. In such 
cases, Novartis should be notified of this action and the IRB/IEC at the study site should be 
informed within 10 working days or less, if required by local regulations.  
12 
References 
References are available upon request. 
Blauvelt A, Prinz JC, Gottlieb AB, Kingo K, Sofen S et al. Secukinumab Administration by 
Pre-filled Syringe: Efficacy, Safety, and Usability Results from a Randomized Controlled 
Trial in Psoriasis (FEATURE). Br J Dermatol. 2014 Aug. 16 [Epub ahead of print] 
Chobanian AV, Bakris GL and Black HR. Seventh report of the joint national committee on 
prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 2003; 
42:1206–1252. 
Chularojanamontri L, Griffiths, CEM and Chalmers JG. The Simplified Psoriasis Index (SPI): 
A Practical Tool for Assessing Psoriasis. J Inv Dermatol 2013; 133:1956-1962. 
Chularojanamontri L, Griffiths, CEM and Chalmers JG. Responsiveness to Change and 
Interpretability of the Simplified Psoriasis Index. J Inv Dermatol 2013; 133. 
Doherty, S. D., A. Van Voorhees, M. G. Lebwohl, N. J. Korman, M. S. Young, S. Hsu and F. 
National Psoriasis (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): 209-217. 
Feldman SR, Fleischer AB jnr, Reboussin DM, Rapp SR, Exam ML, Clarke AR et al. The 
self-administered psoriasis area and severity index is valid and reliable. J Inv Dermatol 
1996;106:183-186. 
Finlay AY and Khan GK. Dermatology Life Quality Index (DLQI): a simple practical  
measure for routine clinical use. Clin Exp Dermatol 1994; 19: 210-216. 


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Fleischer AB jnr, Rapp SR, Reboussin DM, Vanarthos JC and Feldman SR. Patient 
measurement of psoriasis disease severity with a structured instrument. J Inv Dermatol 1994; 
102: 967-969. 
Fredriksson T and Pettersson U. Severe psoriasis-oral therapy with a new retinoid. 
Dermatologica 1978;157:238-44. 
Gottlieb AB, Griffiths CEM, Ho VC, Lahfa M, Mrowietz U, Murrell DF et al. Oral 
pimecrolimus in the treatment of moderate to severe chronic plaque-type psoriasis: a 
double-blind, multicentre, randomized, dose-finding trial. Br J Dermatol. 2005;152:1219-
1227. 
Langley R, Elewski B, Lebwohl M, Reich K, Griffiths C et al. Secukinumab in Plaque 
Psoriasis:- Resiults of two Phase Three Trials. N Engl J Med, 2014; epub DOI: 
10.1056/NEJMoa1314258 
Lebwohl M, Swensen A, Nyiradi J, Kim E, Gwaltney J et al. The Psoriasis Symptom Diary: 
development and content validity of a novel patient-reported outcome instrument. Int J of 
Dermatol. 2014; 53 (6) :714-22  
Manuel, O. and D. Kumar (2008). "QuantiFERON-TB Gold assay for the diagnosis of latent 
tuberculosis infection." Expert Rev Mol Diagn 8(3): 247-256. 
Ramsay B1, Lawrence CM. Measurement of involved surface area in patients with psoriasis. 
Br J Dermatol. 1991;124:565-750. 
Rich P, Sugurgeirsson B, Thaci D, Ortonne JP, Paul C et al. Secukinumab Induction and 
Maintenance Therapy in Moderate-to-Severe Plaque Psoriasis: a Randomized, Double-blind, 
Placebo-controlled, Phase II Regimen –finding Study. Br J Dermatol. 2012; 168: 402-411. 
Schäfer I, Hacker J, Rustenbach SJ,  Radtke M, Franzke N, and Augustin M. Concordance 
of the Psoriasis Area and Severity Index (PASI) and patient-reported outcomes in psoriasis 
treatment. Eur J Dermatol 2010; 10:62-67. 
Weisman S, Pollack CR and Gottschalk RW. Psoriasis disease severity measures: comparing 
efficacy of treatments for severe psoriasis. J Dermatolog Treat 2003; 14:158-165. 
 
 


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13 
Appendices 
13.1 
Appendix 1: SPI questionnaire 
 


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13.2 
Appendix 2 : PASI score 
 


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13.3 
Appendix 3: SA-PASI score 
 
 
 


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13.4 
Appendix 4 : DLQI questionnaire 
 


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13.5 
Appendix 5 : Pain, itching and scaling assessment  
 


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13.6 
Appendix 6 : BISF-M 


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13.7 
 Appendix 7 : BISF-W 
 
 


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13.8 
Appendix 8: Normal ranges of values for vital signs 
Normal blood pressure will be defined as a systolic pressure of 90 to <120 mmHg, and a 
diastolic blood pressure of 60 to <80 mmHg under the measurement conditions outlined 
above. Notable blood pressure will be hypertension (systolic ≥140 mmHg and/or diastolic 
≥ 90 mmHg) or hypotension (systolic <90 mmHg and/or diastolic <60 mmHg). A blood 
pressure indicative of prehypertension (systolic 120 to < 140 mmHg and/or diastolic 80 to 
< 90 mmHg) will not be regarded as notable (Chobanian et al. Hypertension 2003). A normal 
pulse rate will be defined as a rate of 60 to 100 beats per minute under the measurement 
conditions outlined above. Notable pulse rates are a rate below 60 bpm (bradycardia) or above 
100 bpm (tachycardia). 
13.9 
Appendix 9: Clinically notable laboratory findings 
The following criteria will be used to define expanded limits and notable abnormalities of key 
laboratory tests. Notable values for blood pressure and pulse are presented in Section 6.6.2. 
Whether action needs to be taken to address notable laboratory or vital signs values will be 
decided by the investigator, taking into account the overall status of the patient. No 
specification is foreseen as part of the study protocol. 
 
Variable 
Limit 
Liver Function and Related Variables 
Alanine transaminase (ALT) (SGPT) 
> 3 x ULN 
Aspartate transaminase (AST) (SGOT) 
> 3 x ULN 
Total bilirubin 
> 2 x ULN 
Alkaline phosphatase 
> 2.5 x ULN 
Renal Function and Electrolyte Variables 
Creatinine (serum) 
> 1.5 x ULN 


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Potassium 
> 6 mmol/L or < 3 mmol/L 
Sodium 
> 160 mmol/L or < 115 mmol/L 
Hematology Variables 
Hemoglobin 
≥ 20 g/dL decrease from Baseline 
Platelet count 
< 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 
++* 
ULN: Upper Limit of Normal 
LLN: Lower Limit of Normal 
* ++ corresponds to ≥ 100 mg/dL 
 
 

SAP_001.pdf: 
 
 
 
 
 
 
 
Clinical Development 
 
 
 
 
Secukinumab, AIN457 
 
 
 
 
CAIN457AFR01 / NCT02595970 
 
 
 
A 52-week (plus extension until commercialization), single- 
arm study to evaluate psoriasis severity and its 
psychosocial impact using the Simplified Psoriasis Index at 
16 weeks, as well as long-term safety, tolerability and 
efficacy of secukinumab administered subcutaneously in 
patients suffering from moderate to severe psoriasis 
 
 
 
 
 
 
Statistical Analysis Plan (SAP) 
 
Author:                      
 
 
Document type:        SAP Documentation 
 
Document status:      Final version 1.0 
 
Release date:           10-Apr-2017 
 
Number of pages:     28 
 
 
 
 
 
 
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 
 
 
Version 
Date 
Change 
Final v1 
10-APR-2017 


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Table of contents 
Table of contents ................................................................................................................. 3 
List of abbreviations ............................................................................................................ 5 
1     Introduction ......................................................................................................................... 7 
1.1      Study design............................................................................................................. 7 
1.2      Study objectives and endpoints ............................................................................... 8 
1.2.1        Primary objective .................................................................................... 8 
1.2.2        Secondary objectives............................................................................... 8 
1.2.3        Exploratory objectives ............................................................................ 9 
2     Statistical methods ............................................................................................................... 9 
2.1      Data analysis general information ........................................................................... 9 
2.1.1        General definitions .................................................................................. 9 
2.2      Analysis sets .......................................................................................................... 11 
2.2.1        Subgroup of interest .............................................................................. 12 
2.3      Patient disposition, demographics and other Baseline characteristics................... 12 
2.3.1        Patient disposition ................................................................................. 12 
2.3.2        Protocol deviations ................................................................................ 12 
2.3.3        Demographics and other Baseline characteristics ................................. 13 
2.3.4        Medical history and current medical conditions ................................... 13 
2.4 
Treatments (study treatment, rescue medication, concomitant therapies, 
compliance)............................................................................................................ 14 
2.4.1        Study treatment ..................................................................................... 14 
2.4.2        Prior, concomitant and post therapies ................................................... 14 
2.5      Analysis of the primary objective .......................................................................... 15 
2.5.1        Primary endpoint ................................................................................... 15 
2.5.2        Statistical hypothesis, model, and method of analysis .......................... 15 
2.5.3        Handling of missing values/censoring/discontinuations ....................... 15 
2.5.4        Supportive/sensitivity analyses ............................................................. 16 
2.6      Analysis of the key secondary objective ............................................................... 16 
2.6.1        Key secondary endpoint ........................................................................ 16 
2.6.2        Statistical hypothesis, model, and method of analysis .......................... 16 
2.6.3        Handling of missing values/censoring/discontinuations ....................... 16 
2.6.4        Supportive/sensitivity analyses ............................................................. 16 
2.7      Analysis of secondary efficacy objectives ............................................................. 16 
2.7.1        Secondary endpoints ............................................................................. 17 
2.7.2        Statistical hypothesis, model, and method of analysis .......................... 17


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2.7.3        Handling of missing values/censoring/discontinuations ....................... 18 
2.8      Safety analyses....................................................................................................... 18 
2.8.1        Adverse events (AEs)............................................................................ 18 
2.8.2        Deaths.................................................................................................... 19 
2.8.3        Laboratory data ..................................................................................... 19 
2.8.4        Other safety data ................................................................................... 19 
2.9      Pharmacokinetic endpoints .................................................................................... 20 
2.10    PD and PK/PD analyses......................................................................................... 20 
2.11    Biomarkers............................................................................................................. 20 
2.12    Other exploratory analyses .................................................................................... 20 
2.13    Interim analysis...................................................................................................... 21 
3     Sample size calculation ..................................................................................................... 21 
4     Change to protocol specified analyses .............................................................................. 21 
5     Appendix ........................................................................................................................... 21 
5.1      Imputation rules ..................................................................................................... 21 
5.1.1        AE date imputation ............................................................................... 21 
5.1.2        Concomitant medication date imputation ............................................. 23 
5.2      Calculation of Dermatology Life Quality Index (DLQI) ...................................... 24 
5.3      Calculation of  Brief Index of Sexual Functioning for men and woman (BISF- 
M and BISF-W) ..................................................................................................... 26 
5.4      SAS code ............................................................................................................... 27 
6     Reference ........................................................................................................................... 28


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List of abbreviations 
AE                         Adverse event 
ATC                      Anatomical Therapeutic Classification 
AUC                      Area under the curve 
BISF-m                 Brief Index of Sexual Functioning for men 
BISF-w                  Brief Index of Sexual Functioning for woman 
BMI                       Body mass index 
BSA                      Body surface area 
CI                          Confidence Interval 
CSR                      Clinical Study Report 
CT                         Computerized tomography 
DBL                       Database lock 
DLQI                     Dermatology Life Quality Index 
ECG                      Electrocardiogram 
EOE                      End of Extension 
EOT                      End of Treatment 
FAS                       Full Analysis Set 
i                             Intervention 
IGA                       Investigator's Global Assessment 
IS                          Included Set 
LOCF                    Last Observation Carried Forward 
LPLV                     Last Patient Last Visit 
MedDRA               Medical Dictionary for Regulatory Activities 
MRI                       Magnetic resonance imaging 
NovDTD                Novartis Drug and Therapy Dictionary 
p                            Psychosocial 
PASI                     Psoriasis Area and Severity Index 
PFS                       Pre-filles syringe 
PLS                       Product Lifecycle Service 
PPS                      Per Protocol Set 
proSPI                  Professionally-administratored Simplified Psoriasis Index 
PT                         Preferred term 
QFT                      QuantiFERON®-TB 
ROC                      Receiver Operating Characteristic 
s                            Severity 
SAE                      Serious adverse event 
SAF                       Safety Analysis Set 
SAP                      Statistical Analysis Plan 
saPASI                 Self-administratored Psoriasis Area and Severity Index 
saSPI                    Self-administratored Simplified Psoriasis Index 
SD                         Standard deviation 
SE                         Standard error 
SOC                      System organ class


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SPI                        Simplified Psoriasis Index 
TEAE                    Treatment-emergent adverse events


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1          Introduction 
 
The purpose of this Statistical Analysis Plan (SAP) is to describe the statistical methods planned  
in  Section  9  of  the   study  protocol  version  5  of  phase  IIIb  clinical  trial 
CAIN457AFR01 along with any additional analyses, specifications or deviations from  this 
protocol planned before database lock (DBL). Determination of sample size is specified in 
Section 3. 
 
This document is written in the future tense. It will be reviewed and updated (including 
conversion to past tense) for entry into the clinical study report afte r the analysis has taken 
place. 
 
1.1        Study design 
 
This is an open-label multicenter, single arm study in 120 patients with moderate to severe 
psoriasis. There will be no randomization nor interim analysis for this study. 
 
The study consists of five epochs: 
        Screening to occur between day -28 and day -7 
        Treatment 
o Treatment period 1 
o Treatment period 2 
        Extension treatment period 
        Follow-up 
 
There will be an initial induction phase (5 weekly inje ctions) before switching to monthly 
injections until Week 16. The patient will continue with monthly injections until Week 48 in 
case  of  a  favorable  response  to  treatment  at  W eek  16.  Patients  who  are  deemed  to  be 
benefiting from the study drug after 48 weeks of treatment could be continuously treated until 
3 November 2016 or until commercialization of Cosentyx® in France, whichever occurs first. 
 
An illustration of the study design is depicted in Figure 1.1.


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Figure 1-1          Study design 
 
 
 
1.2        Study objectives and endpoints 
 
1.2.1       Primary objective 
 
The primary objective is to evaluate the benefit of secukinumab on the severity of psoriasis 
based on the Simplified Psoriasis Index (SPI). This index comprises 3 components: severity 
(s), psychosocial (p), and intervention (i). All components of SPI will be evaluated by both the 
physician (proSPI) and the patient (self-assessed: saSPI). Only the severity component will be 
evaluated for the primary objective , i.e. both proSPI (s) and saSPI (s). 
 
1.2.2       Secondary objectives 
 
Key secondary objectives are: 
 to assess Psoriasis Area and Severity Index (PASI) weekly from week 0 to 4 then 
every 4 to 8 weeks until Week 56 
        to evaluate correlation between PASI and proSPI (s) 
Other secondary objectives include: 
 to assess proSPI (s, p and i) over time (weekly from Week 0 to Week 4 then every 4 
to 8 weeks until Week 56). 
        to assess saSPI (s, p and i) over time (weekly from Week 0 to Week 4 then every 4 to 
8 weeks until Week 56). 
        to assess Dermatology Life Quality Index (DLQI) over time (weekly from Week 0 to 
Week 4 then every 4 to 8 weeks until Week 56). 
 to assess self-administered PASI (saPASI) (weekly from Week 0 to Week 4 then 
every 4 to 8 weeks until Week 56). 
 to assess pain, itching, and scaling using the Psoriasis Symptom Diary questionnaire 
over time (weekly from Week 0 to Week 4 then every 4 to 8 weeks until Week 56).


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        to evaluate correlation between proSPI (for each component separately: s, p, i) and 
DLQI 
        to evaluate correlation between proSPI (p, i separately) and PASI 
 to evaluate safety during the treatment period (until the Week 52) and during the 
extension treatment period (after the Week 52) 
 
1.2.3       Exploratory objectives 
        to evaluate correlation between saSPI (s, p, i separately) and DLQI. 
        to evaluate correlation between proSPI (s, p separately) and saSPI (s, p separately). 
        to evaluate correlation between saSPI (s) and PASI. 
 to evaluate the ability of SPI to discriminate between responders and non-responders 
based on PASI response. 
 to explore sexual dysfunction using the Brief Index of Sexual Functioning for 
men/woman (BISF-m or BISF-w) questionnaire in a subset of subjects willing to 
complete sexual function questionnaire. 
 
2          Statistical methods 
 
2.1        Data analysis general information 
 
The analysis will be performed by Novartis. The statistical software used for the analyses will 
be SAS version 9.4 or later. 
 
Descriptive statistics for continuous variables in the study will include the number of 
observations,  mean,  standard  deviation  (SD),  median,  minimum,  and  maximum.  The 
following number of decimal places will be used: mean,  and median, values to 1 more 
decimal place than the raw data; minimum and maximum to the same number of decimal places 
as the raw data and SD to 2 more decimal places than the raw data. 
 
For categorical variables frequency and percentage will be presented for non-missing data. 
If appropriate, 95% Confidence Intervals (CIs) will be presented along with p-values. 
Unless otherwise specified, all statistical tests will be two -sided and will use the 5% level of 
significance. 
 
All data will be listed by patient unless stated otherwise. 
 
2.1.1       General definitions 
 
2.1.1.1    Study treatment 
 
The investigational drug, secukinumab, is to be injected subcutaneously and will be provided 
by Novartis in pre-filled syringes (PFS) of 150 mg. Two injections will therefore be necessary 
to obtain the required dosage of 300 mg.


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2.1.1.2    Study day 
 
The day of first administration of the treatment will be considered as study day 1. All other 
study day will be labeled relative to study day 1. 
 
The day for a particular event on or after the study day 1 will be calculated as: 
 
date of event – date of first dose + 1 
 
The day before study day 1 will be calculated as: 
 
date of event – date of first dose 
 
2.1.1.3    Baseline and post-Baseline 
 
Baseline data will be defined as the last available non -missing data collected prior to the first 
study treatment  administration. Data collected after first dose of study treatm ent will be 
considered as post-Baseline data. 
 
Change from Baseline will only be summarized for patients with both Baseline and post- 
Baseline unless stated otherwise, and it will be calculated as: 
 
post-Baseline value – Baseline value 
 
Correspondingly, percentage change will be calculated as: 
 
100 * (post-Baseline value – Baseline value) / Baseline value 
 
2.1.1.4    Visit windows 
 
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 in this study 
are shown in Table 2-1. In this table, the days are counted since the first dose of study treatment.  
These  visit  windows  apply to  measurements  taken  at  every  visit.  When  visit windows 
are used, all visits (except follow up visits) will be re-aligned, i.e., they will be mapped into 
one of the visit windows. E.g., if the Week 4 visit of a subject is delayed and occurs on Day 46 
instead of on Day 29, say, it will be re -aligned to visit window Week 8. If two visits fall into 
one window then the visit closest to target scheduled day will be analysed for that visit. Follow 
up visits will not be re-aligned. 
 
Table 2-1            Assessment windows for scheduled visits 
 
Visit 
Week 
Scheduled day 
Visit Window 
Baseline 
0 
1 
-28 days to day 1 
Visit 2 
1 
8 
Day 2-11 
Visit 3 
2 
15 
Day 12-18 
Visit 4 
3 
22 
Day 19-25 
Visit 5 
4 
29 
Day 26-43 
Visit 6 
8 
57 
Day 44-71 
Visit 7 
12 
85 
Day 72-99 


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Visit 
Week 
Scheduled day 
Visit Window 
Visit 8 
16 
113 
Day 100-141 
Visit 9 
24 
169 
Day 142-197 
Visit 10 
32 
225 
Day 198-253 
Visit 11 
40 
281 
Day 254-309 
Visit 12 
48 
337 
Day 310-351 
Visit 13 
52 
365 
Day 352-379 
Extension 1 
56 
393 
Day 380-421 
Extension 2 
64 
449 
Day 422-477 
Extension 3 
72 
505 
Day 478-533 
Follow-up 
80 
561 
≥ Day 534 
 
2.1.1.5    Follow up visit 
 
Efficacy data collected at follow up visits will not be summarized. 
Efficacy data collected at follow up visits will be listed. 
 
2.1.1.6    Unscheduled visit 
 
All  safety  and  exposure  to  study treatment  data  collected  at  unscheduled  visits  will  be 
summarized. 
 
Efficacy data collected at unscheduled visits will be visit windowed as per section 2.1.1.4 and 
will be presented in the same manner as scheduled visits. 
 
All data collected at unscheduled visits will be listed. 
 
2.2        Analysis sets 
 
The following analysis sets will be used in this study: 
 
Included Set (IS): The included set will comprise all patients included in the study. A patient 
is considered to be included in the study if he/she successfully completes the screening period. 
Completion of screening period is defined as patient who has “Will the subject continue into the 
Treatment phase?” equal to “Yes” from the Screening Phase Disposition eCRF page. 
 
Full Analysis Set (FAS): The FAS will comprise all patients in the IS who are administered 
with at least one dose of investigational drug with at least one Baseline and one post-Baseline 
SPI evaluation. 
 
The primary analysis will be performed on the FAS. 
 
Safety  Analysis  Set  (SAF):  The  SAF  will  comprise  all  patients  in  the  IS  who  are 
administered with at least one dose of investigational drug during the treatment period. 
 
Per Protocol Set (PPS): The PPS will comprise all patients in the FAS without any major 
protocol deviation. 
 
Analysis sets for specific outputs are given in Table 2-2.


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Table 2-2            Analysis data sets for specific outputs 
 
Table                                                                IS                 FAS          SAF          PPS 
Concomitant medication                                                                         x 
Demographics and Baseline characteristics    x 
Exposure                                                                                                x 
Medical history                                                 x 
Other efficacy analyses                                                        x 
Patient disposition                                            x 
Patient reported outcomes                                                   x 
Primary and key secondary efficacy 
variables                                                                               x                                  x 
Protocol deviations                                           x 
Safety analyses                                                                                      x 
 
The number and percentage of patients in each analysis set will be summarized based on the 
IS. 
 
If protocol deviations (PDs) occur, then the data from specific patients, visits, or evaluations 
may be excluded from analysis. The criteria and determination of clinically significant PDs 
leading to exclusion from PPS will will be finalized prior to DBL and analysis. 
 
2.2.1       Subgroup of interest 
 
N/A 
 
2.3 
Patient disposition, demographics and other Baseline 
characteristics 
 
2.3.1       Patient disposition 
 
Patient disposition will be presented in listings. 
 
The total number and percentage of subjects passing and failing screening be presented. 
 
The number and percentage of patients who completed study periods (treatment period 1, 
treatment period 2, and extension treatment period) or discontinued the study prematurely 
including the reason for discontinuation will be presented by study periods for all subjects in 
the IS. 
 
A schematic diagram of subject disposition will be provided. 
 
2.3.2       Protocol deviations 
 
The number and percentage of subjects with PDs will be tabulated by deviation category. A 
table with only major PDs and criteria leading to exclusion from analysis sets will also be 
presented. In both tables, subjects with multiple PDs will only be counted once at each level 
of summarization. 
 
In addition, a listing of PDs will be produced including the accompanying deviation code.


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Classification of which PDs will lead to exclusion from analysis sets will be agreed and 
documented in a data review meeting prior to database lock. 
 
2.3.3       Demographics and other Baseline characteristics 
 
Descriptive statistics for the following data and will be provided (including Baseline values of 
the main efficacy endpoints) for the IS population. 
 
Demographics and background characteristics: 
        age (in years, and year categories ≤ 65, > 65) 
        gender (male/female) 
 child bearing status (able to bear children/post menopausal/sterile - of child bearing 
age) 
        race (Caucasian/Black/Asian/native American/Pacific islander/other) 
        smoking status (never/current/fomer) 
        average pack year (former/current/overall) 
        height (cm) 
        weight (kg) 
        body mass index (BMI) = weight ( kg) / (height ( meters))2 
        sitting pulse (bpm) 
        systolic and diastolic blood pressure (mmHg) 
        pregnancy test (negative/positive/not done/unknown) 
        education level (none/primary education/secondary education/university) 
Disease history and Baseline disease characteristics: 
        total body surface area (BSA) affected 
        Baseline PASI 
        time since diagnosis of plaque type psoriasis (years) 
        Baseline Investigator Global Assessment (IGA) 
        Baseline saPASI 
        previous exposure to psoriasis therapy 
 
The following data will also be summarized: 
        standard 12-lead Electrocardiogram (ECG) at Baseline. 
        QuantiFERON®-TB Gold In-Tube assay (QFT) at screening (positive / negative / 
indeterminate) 
        X-ray (or Magnetic resonance imaging (MRI), computerized tomography (CT) scan) 
at screening 
 
2.3.4       Medical history and current medical conditions 
 
Analysis of medical history and current medical conditions will be based on the IS. General 
medical history, and current medical conditions collected in the CRF will be coded using the


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Medical   Dictionary   for   Regulatory   Activities   (MedDRA)   dictionary.   They   will   be 
summarized by system organ class (SOC) and preferred term (PT) of the MedDRA dictionary. 
 
Psoriasis specific medical history will be summarized by predefined types of psoriasis collected 
on the CRF where the number a nd percentage of patients with each type will be presented. 
In addition, time since diagnosis will be summarizied for the following catogeries: 
≤ 1 year, > 1 and ≤ 5 years,  < 5 and ≤ 10 years, < 10 and ≤ 20 years, and > 20 years. 
 
2.4 
Treatments (study treatment, rescue medication, concomitant 
therapies, compliance) 
 
2.4.1       Study treatment 
 
The analysis of study treatment data will be based on the SAF. 
 
Duration of exposure is defined as the time from first dose of study treatment to the time of 
end of study day. For subjects who discontinue this will be the last visit in the corresponding 
treatment period. The duration of exposure to study treatments (days) will be calculated as: 
 
end of study date – start date of study treatment + 1 
 
The duration in days will be summarized using frequencies and percentables for categories: ≤ 
4 weeks, > 4 ≤ 16 weeks, > 16 ≤ 52 weeks, > 52 ≤ 72 weeks, and > 72 weeks. 
 
The number of percentage of subjects with dose amount < 300mg, 300mg, and > 300mg will 
be provided. 
 
2.4.2       Prior, concomitant and post therapies 
 
Prior or concomitant medication will be identified based on recorded or imputed start and end 
dates of medication taken. Prior (or previous) medication is defined as a treatment taken but 
stopped prior to first administration of investigational drug. Concomitant medication is any 
medication administered at least once between the day of first injection of investigational drug 
and the last day of study visit, including a medication initiated pre -screening and ongoing at 
the start of the treatment period. 
 
Medications will be identified using the Novartis Drug and Therapy Dictionary (NovDTD) 
including Anatomical Therapeutic Chemical (ATC) code. Prior and concomitant treatments will 
be summarized for the SAF. 
 
Prior  and  concomitant  medications will be summarized in separate tables.  They will be 
presented for the whole study period. 
 
Medications will be presented in alphabetical order, by PT and grouped by anatomical main 
group. Tables will also show the overall number an d percentage of patients receiving at least 
one treatment of a particular PT and at least one treatment in a particular anatomical main group. 
 
By-patient listings for prior and concomitant medications will be provided. 
Prior psoriasis therapy will be summarized overall, by type and PT.


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2.5        Analysis of the primary objective 
 
The primary objective is to evaluate the ben efit of secukinumab on the severity of psoriasis 
based on the severity component of the SPI at Week 16. 
 
2.5.1       Primary endpoint 
 
The co-primary variables are: 
        change from Baseline in proSPI (s) Week 16 
        change from Baseline in saSPI (s) at Week 16 
 
The primary analysis will be based on the FAS. 
 
2.5.2       Statistical hypothesis, model, and method of analysis 
 
The following hypothesis will be tested for each co-primary endpoint at the 5% significance 
level (2-sided): 
 
H0: µd = 0 
 
HA: µd ≠ 0 
 
where µd denotes the mean difference of paired observations. 
 
To assess the primary objective, the absolute change from Baseline in proSPI (s) and absolute 
change from Baseline in saSPI (s) will be analyzed using a paired t-test (Week 16 vs Baseline). 
 
The key assumptions underlying the use of a paired t -test will be checked. In the event the 
data is non-normal, Wilcoxon signed rank test will be performed. 
 
An adjustment for multiplicity will be performed using the Hochberg procedure and the family-
wise type-I-error will be set to α=5% (2 -sided). The adjustment will be applied as follows; 
if the maximum of the two p -values is rejected at the 5% level (2 -sided) then both hypotheses 
are rejected and statistical significance is claimed for both endpoints. Otherwise if the maximum 
of the two p-values is not rejected, then the minimum p -value is tested at the 
2.5% level (2-sided), if rejected then statistical significance is claimed only for this endpoint. 
 
Descriptive  statistics  of  proSPI  (s)  and  saSPI  (s)  ( Baseline,  actual  value,  absolute  and 
percentage change from Baseline) will be presented by visit for severity score and its 
components 1A and 1B. The number and percentage of reponses for 1A will be presented by 
body part. The change from Baseline of proSPI (s) and saSPI (s) will be presented graphically, 
showing the mean and SE of the change per visit. 
 
The number and percentage of proSPI (s) and saSPI (s)  will be presented by visit and by the 
following score bands: from 0 to 10, > 10 and ≤ 20, > 20 and ≤ 30, > 30 and ≤ 40, > 40 and ≤ 
50. Graph of reponse distribution  of proSPI   (s) and  saSPI (s) will be presented by the 
aforementioned score bands at Week 16. 
 
2.5.3       Handling of missing values/censoring/discontinuations 
 
Missing data will be imputed using Last Observation Carried Forward (LOCF) method. This 
approach will consist of replacing the missing W eek 16 assessment by the last non-missing 
assessment value.


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2.5.4       Supportive/sensitivity analyses 
 
To assess for robustness of the results, the same analysis as specified in Section 2.5.2 will be 
repeated for the FAS (on observed data). 
 
The primary analysis for the two co-primary endpoints will be also be performed on the PPS. 
 
2.6        Analysis of the key secondary objective 
 
The key secondary objectives of this study are: 
        to assess PASI weekly from week 0 to 4 then every 4 to 8 weeks until end of study 
        to evaluate correlation between PASI and proSPI (s) 
 
2.6.1       Key secondary endpoint 
 
The key secondary variables are: 
        absolute PASI score values at each post-Baseline visit until end of study 
        the correlation coefficient between PASI and proSPI (s) at each post-Baseline visit 
The key secondary endpoints analyses will be based on the FAS (observed data only). 
 
2.6.2       Statistical hypothesis, model, and method of analysis 
 
Descriptive statistics of PASI score (Baseline, actual value, absolute change and percentage 
change from Baseline) will be presented by visit. The percentage change from Baseline of these 
scores will be presented graphically, showing the mean and SE of the percentage change per 
visit. The number and percentage of PASI score will also be presented by body region, 
symptom, and visit. 
 
The number and percentage for each PASI response category (PASI 50 responders, PASI 75 
responders, PASI 90 responders, and PASI 100 responders) will be presented by visit. For 
example, PASI 50 responders are the patients achieving ≥ 50% improvement (reduction) in 
PASI score compared to Baseline. 
 
Change from Baseline to Week 16 of PASI score will be analyzed as for the primary analysis 
described in Section 2.5.2. 
 
For the evaluation of the correlation between PASI and proSPI (s) at each post-Baseline visit 
using Spearman’s correlation coefficient. Scatterplots of PASI and proSPI(s) at Week 16 will 
also be provided. 
 
2.6.3       Handling of missing values/censoring/discontinuations 
 
Analysis and presentations of key secondary objectives will only be based on observed data. 
 
2.6.4       Supportive/sensitivity analyses 
 
N/A 
 
2.7        Analysis of secondary efficacy objectives 
 
All secondary efficacy analysis will be based on the FAS (observed data only).


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2.7.1       Secondary endpoints 
 
The secondary efficacy variables are the following: 
        proSPI (s, p, i) score at all assessment periods 
        saSPI (s, p, i) score at all assessment periods 
        Dermatology life quality index (DLQI) score at all assessment periods 
        saPASI score at all assessment periods 
        Psoriasis Symptom diary at all assessment periods 
 correlation between each of proSPI (s, p, i) and DLQI, and proSPI (p, i) and PASI, at 
all assessment periods 
 
2.7.2       Statistical hypothesis, model, and method of analysis 
 
ProSPI and saSPI 
 
Descriptive statistics of absolute values and change from Baseline at all assessment periods 
for proSPI (s, p, i) and saSPI (s, p, i) will be presented separately. 
 
The number and percentage of proSPI (p, i) and saSPI (p, i)  will be presented by visit and by 
the following score bands: 0, 1, 2, …, 9, 10. Graph of reponse distribution of proSPI  (p, i) 
and saSPI (p, i) will be presented by the aforementioned score band at Week 16. 
 
DLQI 
 
The DLQI contains six functional scales (symptoms and feeling, daily activities, leisure, work 
and school, personal relationships, treatment). 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. Details on 
the calculation of DLQI are given in Appendix 5.2. 
 
For each of the seven scores the percentage change from Baseline at each visit will be derived. 
Summary statistics will be provided for absolute values as well as for the percentage change 
by visit. 
 
Number and percentage of patients achieving DLQI status 0 or 1 will be provided by visit. 
 
SaPASI 
 
Absolute value, absolute change and percentage change from Baseline of saPASI score will 
be summarized by sivit. The number and percentage of saPASI score will be presented by body 
region, symptom, and visit. 
 
 
 
Psoriasis Symptom Diary 
 
Descriptive summary statistics will be presented for absolute values and change from Baseline 
by visit for intensity of pain, itching and scaling separately. 
 
Correlations between scores 
 
Computation of Spearman’s correlation coefficient at each post-Baseline visit and graphing of 
scatterplot at Week 16 will be performed on the following scores: 
        between proSPI (s, p, i) and DLQI (total score)


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        between proSPI (p, i) and PASI 
 
2.7.3       Handling of missing values/censoring/discontinuations 
 
Missing values for the secondary variable will not be replaced. Subjects with no post-Baseline 
value will be excluded from this analysis. 
 
2.8        Safety analyses 
 
Analysis of safety data will be on the SAF. 
 
2.8.1       Adverse events (AEs) 
 
AEs will be presented for the whole study period. 
 
Only AEs that are treatment emergent are summarized. Treatment emergents are defined as 
events started after the first dose of study medication or events present prior to the first dose 
of study medication but increased in severity, frequency or clinical feature based on PT and 
started prior to end of study. 
 
Treatment-emergent adverse events (TEAEs) will be included in all summaries and listings. 
AEs occurring after signing of informed consent but before first dose of study treatmen t and 
those occurring after study completion will be listed only. If any event has an incomplete 
onset date, this will be handled as described in Appendix  5.1. 
AEs will be coded by primary SOC and PT according to the MedDRA version 19.1 or later. 
AEs will be summarized by presenting the number and percentage of patients having any AE, 
having an AE by SOC, and having an AE by PT. Summaries will also be presented for AEs 
by severity, study treatment related AEs, serious adverse events (SAEs), AE’s leading to 
study drug discontinuation, and AE’s leading to death. 
 
Patients who experienced multiple AEs for a PT will be counted once, similarly for patients 
with multiple AEs per SOC. If a particular AE ‘severity’ is missing, this variable will be listed 
as missing and treated as missing in summaries. If a patient reports more than one AE with the 
same PT, only the greatest severity will be presented for this AE. If a patient reports more 
than one AE within the same primary SOC , the patient will be counted only once with the 
highest severity at the SOC level, where applicable. 
 
For the legal requirements of clinicaltrials.gov and EudraCT, two required tables on TEAEs 
with an incidence greater than 5% and on treatment emergent SAEs and SAE suspected to be 
related to study treatment will be provided by SOC and PT on the SAF. 
 
If for a same patient, several consecutive AEs (irrespective of study treatment causality, 
seriousness, and severity) occurred with the same SOC and PT: 
 
 a single occurrence will be counted if there is  ≤ 1 day gap between the end date of the 
preceding AE and the start date of the consecutive AE 
 
 more than one occurrence will be counted if there is > 1 day gap between the end date 
of the preceding AE and the start date of the consecutive AE


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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. 
 
A listing of all AEs will be presented. A column indicating if the AE is treatment emergent or 
not will be shown. Non-treatment emergent AEs will not be summarized; they will only be 
listed in final analysis. 
 
2.8.1.1    Adverse events of special interest / grouping of AEs 
 
N/A 
 
2.8.2       Deaths 
 
AEs that lead to death are outlined in Section 2.8.1. 
 
2.8.3       Laboratory data 
 
The summary of the data for laboratory evaluations will be presented for both types of 
laboratory tests (hematology and biochemistry). 
 
Descriptive summary statistics for the absolute values and changes from Baseline at each 
study visit will be presented. Descriptive summaries will be presented by type and by laboratory 
test. 
 
For each parameter, shift tables will be produced in order to compare patient Baseline laboratory 
evaluation with the observed value at each visit. For these shift tables, the normal laboratory 
ranges will be used to evaluate whether a particular laboratory test value is normal, low, or high 
at each visit relative to whether or not the Baseline value was normal, low, or high. These 
summaries will be presented by laboratory test. 
 
The expanded laboratory ranges and the clinically notable abnormalities of key l aboratory 
tests are given in Appendix 9, Section 13.9 of the study protocol version 5. 
 
2.8.4       Other safety data 
 
2.8.4.1    ECG and cardiac imaging data 
 
N/A in this section (see Section 2.3.3). 
 
ECG collected at screening will be summarized as part of Baseline characteristics (see Section 
2.3.3) 
 
2.8.4.2    Vital signs 
 
Vital signs will be presented for the whole study period. Analysis of the vital sign 
measurements using summary statistics for the ab solute values and changes from Baseline at 
each non-missing post-Baseline visit will be performed. These descriptive summaries will be 
presented by vital sign parameter.


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The number and the percentage of subjects with notable vital signs will be presented. The 
criteria for notable vital sign abnormalities are provided in Appendix 8, Section 13.8 of the 
study protocol version 5. 
 
All information collected will be listed by patient and visit. Notable abnormal values will be 
flagged. 
 
2.9        Pharmacokinetic endpoints 
 
N/A 
 
2.10      PD and PK/PD analyses 
 
N/A 
 
2.11      Biomarkers 
 
N/A 
 
2.12      Other exploratory analyses 
 
Exploratory analyses in this subsection will be on the FAS (observed data only). 
 
Correlations between scores 
 
Correlations between saSPI (s, p, i)  and DLQI, proSPI (s, p) and saSPI (s, p), saSPI (s) and 
PASI, proSPI (s) and saPASI, saSPI (s) and saPASI will be evaluated using the Spearman 
correlation coefficient. Scatterplots will be presented at Week 16. 
 
Responsiveness to change 
 
An  analysis  of  the  SPI  responsiveness  to  change  will  be  led  in  order  to  investigate  if 
reductions   in   psoriasis   severity   based   on   PASI   scores   would   be   accompanied   by 
corresponding reductions in proSPI (s) and saSPI (s) scores at Week 16. This analysis will be 
performed by the calculation of receiver operating characteristic (ROC) and area under the 
curve (AUC). Three criteria of response will be examined to evaluate each score:  ≥50%, 
≥75%, ≥90%, and 100% reduction in PASI score. 
 
For each binary PASI response (e.g. for PASI75, 1 if ≥75% and 0 otherwise), a logistic 
regression will be performed where proSPI (s) and saSPI (s) are the independent variables in 
separate models. The nonparameteric methods described in DeLong et al. (1988) will be used 
to compute the AUC value and 95% CIs for each curve. From the regression models, odds ratios 
along with their 95% CIs, and AUC values along with their 95% CIs will be presented. 
 
Sexual dysfunction 
 
To explore sexual dysfunction in the subset of patients willing to complete sexual function 
questionnaire, descriptive summary statistics will be presented for absolute values and change 
from Baseline for BISF-m and BISF-w scores at all assessment periods. 
 
Each of the BISF-m and BISF-w index contain seven dimensions (thoughs/desire, arousal, 
frequency of sexual activity, receptivity/initiation, pleasure/orgasim, relationship satisfaction, 
problems affecting sexual function). Eight scores will be derived from the answers to the


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questionnaires: the score of each of the s even dimensions as well as the composite score 
computed from all dimensions. Details of the calculation are given in Appendix 5.3. 
 
2.13      Interim analysis 
 
No interim analysis is planned in this study. 
 
3          Sample size calculation 
 
The samples size calculation is based on the primary objective of the study which is to 
evaluate the benefit of secukinumab on the severity and psychosocial burden of psoriasis 
based on SPI change at W eek 16 compared to Baseline in patients suffering from moderate to 
severe plaque psoriasis. 
 
A similar study by Chularojanamontri  et al. (2013) showed that it is possible to detect 
responsiveness and a minimum clinically important difference (an absolute change of 5 and 7 
for proSPI (s) and saSPI (s), respectively) d erived from PASI changes with 100 patients. The 
study showed a SD of 7.35 and 10.35 in change from Baseline at Week 10 in proSPI (s) and 
saSPI (s) respectively. As the SD at Week 16 is expected to be higher, c onservative SD 
estimates of 14 and 19 will be assumed for change at W eek 16 for proSPI (s) and saSPI (s) 
respectively. 
 
Based on an analysis of paired differences, in order to have at least 90% power to detect a 
significant clinical difference for each index at the 2.5% level (2-sided), it can be estimated 
that a sample size of 100 evaluable patients would be sufficient. 
 
Taking into account an anticipated drop-out of 20 patients, 120 patients will need to be included 
in the study. 
 
 
4          Change to protocol specified analyses 
 
Any objectives to be assessed until Week 56 will be changed to until end of study. 
 
 
5          Appendix 
 
5.1        Imputation rules 
 
5.1.1       AE date imputation 
 
The following table explains the notation used in the logic matrix. Please note that completely 
 missing start dates will not be imputed.  
 
 
Day 
Month 
Year 
Partial Adverse Event Start Date 
Treatment Start Date 
Not used 
Not used 
MON 
TRTM 
YYYY 
TRTY 
The following matrix explains the logic behind the imputation. 
 
 
MON MISSING            MON < TRTM          MON = TRTM          MON > TRTM


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MON MISSING 
MON < TRTM 
MON = TRTM 
MON > TRTM 
YYYY MISSING 
( 1 ) 
( 1 ) 
( 1 ) 
( 1 ) 
No convention 
No convention 
No convention 
No convention 
YYYY < TRTY 
( 2.a ) 
( 2.b ) 
( 2.b ) 
( 2.b ) 
Before Treatment 
Start 
Before Treatment 
Start 
Before Treatment 
Start 
Before Treatment 
Start 
YYYY = TRTY 
( 4.a ) 
( 4.b ) 
( 4.c ) 
( 4.c ) 
Uncertain 
Before Treatment 
Uncertain 
After Treatment 
Start 
Start 
YYYY > TRTY 
( 3.a ) 
( 3.b ) 
( 3.b ) 
( 3.b ) 
After Treatment 
After Treatment 
After Treatment 
After Treatment 
Start 
Start 
Start 
Start 
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 < 
investigational study treatment start date then AE start reference date = min(informed 
consent date, earliest visit date). 
2.   Else AE start reference date = investigational study treatment start date 
 
Impute AE start date - 
1.  If the AE start date year value is missing, the date uncertainty is too high to impute a rational 
date. Therefore, if the AE year value is missing, the imputed AE start date is set to NULL. 
2.  If the AE start date year value is less than the treatment start date year value, the AE 
started before treatment. Therefore: 
a.   If AE month is missing, the imputed AE start date is set to the mid -year point 
(01JULYYYY). 
b.  Else if AE month is not missing, the imputed AE start date is set to the mid -month 
point (15MONYYYY). 
c.   If the AE start date year value is greater than the investigational study 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 im puted AE start date is set to the later of 
(month start point (01MONYYYY), AE start reference date + 1 day). 
 
c.   4. If the AE start date year value is equal to the investigational study treatment start date 
year value: 
a.   And the AE month is missing the imputed A E start date is set to the  treatment 
reference start date + 1 day. 
b.  Else if the AE month is less than the investigational study treatment start month, the 
imputed AE start date is set to the mid-month point (15MONYYYY).


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Day 
Month 
Year 
Partial CM Start Date 
Treatment Start Date 
Not used 
Not used 
MON 
TRTM 
YYYY 
TRTY 
The following matrix explains the logic behind the imputation.  
 
 
 
c.   Else if the AE month is equal to the investigational study 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), treatment 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. 
 
5.1.2        Concomitant medication date imputation 
 
5.1.2.1    CM start date imputation 
 
The following table explains the notation used in the logic matrix. Please note that completely 
 missing start dates will not be imputed.              
 
 
 
 
 
 
 
 
MON MISSING 
MON < TRTM 
MON = TRTM 
MON > TRTM 
YYYY MISSING 
( 1 ) 
( 1 ) 
( 1 ) 
( 1 ) 
Uncertain 
Uncertain 
Uncertain 
Uncertain 
YYYY < TRTY 
( 2.a ) 
( 2.b ) 
( 2.b ) 
( 2.b ) 
Before Treatment 
Start 
Before Treatment 
Start 
Before Treatment 
Start 
Before Treatment 
Start 
YYYY = TRTY 
( 4.a ) 
( 4.b ) 
( 4.a ) 
( 4.c ) 
Uncertain 
Before Treatment 
Start 
Uncertain 
After Treatment 
Start 
YYYY > TRTY 
( 3.a ) 
( 3.b ) 
( 3.b ) 
( 3.b ) 
After Treatment 
Start 
After Treatment 
Start 
After Treatment 
Start 
After Treatment 
Start 
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 investigational study 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 investigational study 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 im puted CM start date is set to the month 
start point (01MONYYYY).


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Table 
Score 
Very much 
3 
A lot 
2 
A little 
1 
Not at all 
0 
Not relevant 
0 
Question unanswered 
0 
Yes (Question 7: “prevented work or studying”) 
3 
 
 
4. If the CM start date year value is equal to the investigational study 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 to 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 th an 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 sho uld be set to the (imputed) CM 
end date. 
 
5.1.2.2    CM end date imputation 
1.  If the CM end date year value is missing, the date uncertainty is too high to impute a rational 
date. Therefore, if the CM end year value is missing or ongoing, the imputed CM end date 
is set to NULL. 
2.  Else, if the CM end date month is missing, the imputed end date should be set to the 
earliest of the (treatment follow up period date, 31DECYYYY, date of death). 
3.  If the CM end date day is missing, the imputed end date should be set to the earliest of the 
(treatment follow up period date, last day of the month, date of death). 
4.  If the imputed CM end date is less than the existing CM start date, use the CM start date 
as the imputed CM end date. 
 
5.2        Calculation of Dermatology Life Quality Index (DLQI) 
 
DLQI contains six functional scales (symptoms and feeling, daily activities, leisure, work and 
school, personal relationships, treatment).  Each question will be answered with the following 
response: “not at all”, “a little”, “a lot”, “very much”, or “not relevant”. Seven scores will be 
derived from the DLQI: the 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. 
 
Scoring 
The scoring of each question is as follows:


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The DLQI is 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. The DLQI can 
also be expressed as a percentage of the maximum possible score of 30. 
 
Meaning of DLQI Scores 
 
0-1 = no effect at all on patient’s life 
 
2-5 = small effect on patient’s life 
 
6-10 = moderate effect on patient’s life 
 
11-20 = very large effect on patient’s life 
 
21-30 = extremely large effect on patient’s life 
 
Detailed analysis of the DLQI 
 
The DLQI can be analysed under six headings as follows: 
Section 
Question 
Score 
Symptoms and feelings 
1, 2 
maximum 6 
Daily activities 
3, 4 
maximum 6 
Leisure 
5, 6 
maximum 6 
Work and School 
7 
maximum 3 
Personal relationships 
8, 9 
maximum 6 
Treatment 
10 
maximum 3 
 
The scores for each of these sections can also be expressed as a percentage of either 6 or 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 and the scores are summed and 
expressed as usual out of a maximum of 30. 
2.  If two or more questions are left unanswered the questionnaire is not scored. 
3.  If question 7 is answered ‘yes’ this is scored 3. If question 7 is answered ‘no’ but then 
either ‘a lot’ or ‘a little’ is ticked this is then scored 2 or 1. If “Not relevant” is ticked, 
the score for Question 7 is 0. If it is answered ‘no’, but the second half is left 
incomplete, the score will remain 0. 
4.  If two or more response options are ticked, the response option with the highest score 
should be recorded. 
5.  If there is a response between two tick boxes, the lower of the two score options 
should be recorded. 
6.  The DLQI can be analysed by calculating the score for each of its six sub-scales (see 
above). When using sub-scales, if the answer to one question in a sub-scale is missing, 
that sub-scale should not be scored.


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5.3 
Calculation of  Brief Index of Sexual Functioning for men and 
woman (BISF-M and BISF-W) 
 
The calculation of BISF-W will be based on Mazer et al. (2000). A similar method will be 
adopted for calculation of BISF-M. As per French author recommendations, Dr François Petit 
(email to the CPO on 09/01/2017), BISF -M and W scoring rules for the French questionnaire 
need to be adapted in order to keep the same reference ranges. 
 
Each of the BISF-M and BISF-W index consists of seven dimension scores describing seven 
aspects of sexuality. The dimensions are as follows: 
Dimension (name) 
Question 
Score range 
D1 (thoughts/desire) 
Q3 + Q4 
0 to 12 
D2 (arousal) 
Q5 + Q6 
0 to 12 
D3 (frequency of sexual activity) 
Q7 
0 to 12 
D4 (receptivity/initiation) 
Q8 + Q9 + Q12 
0 to 15 
D5 (pleasure/orgasm) 
Q10 + Q11 
0 to 12 
D6 (relationship satisfaction) 
Q18 + Q19 + Q20 
0 to 12 
D7 (problems affecting sexual function) 
Q14 + Q15 + Q16 + Q17 
0 to 16 
 
Detailed analysis of the answers to questionnaires 
 
Calculation for each of the twenty two questions is as follows. 
Q1. yes/no responses are not scored. 
Q2.   yes/no responses are not scored. 
Q3.   responses are scored as (0) = 0, (1) = 1, (2) = 2, (3) = 3, (4) = 4, (5) = 5, (6) = 6. The 
possible score range is 0 to 6. 
Q4.   responses for each of the seven items are scored as (0) = 0, (1) or (2) = 1, (3) = 3, (4) = 
4, (5) = 5, (6) = 6. The final score is the sum of the item scores divided by 7. The possible 
score range is 0 to 6. 
Q5.   responses for each of the eight items are scored as (0) = 0/not applicable, (1) = 0, (2) = 
1, (3) = 2, (4)= 3, (5) = 4. The final score is the sum of the item scores divided by 4. The 
possible score range is 0 to 8. 
Q6.   responses are scored as (0) = 0/not applicable, (1) = 4, (2) = 3, (3) = 2, (4) = 1, (5) = 0. 
The possible score range is 0 to 4. 
Q7.   responses for each of the eight items for BISF-W (nine items for BISF-M) are scored 
as (0) = 0, (1) = 1, (2) = 2, (3) = 3, (4) = 4, (5) = 5, (6) = 6. The final score for BISF_W and 
BISF_M is the sum of the item scores divided by 4 and 4.5 respectively. The possible score 
range is 0 to 12. 
Q8.   responses are scored as (0) = 0/not applicable, (1) = 0, (2) = 6, (3) = 4, (4) = 2. The 
possible score range is 0 to 6. 
Q9.   responses are scored as (0) = 0/not applicable, (1)= 0/not applicable, (2) = 0, (3) = 1, 
(4) = 2, (5) = 3, (6) = 4, (7) = 5. The possible score range is 0 to 5. 
Q10. responses are scored as (0) = 0/not applicable, (1) = 0/not applicable, (2) = 0, (3) =1, 
(4) = 2, (5) = 3, (6) = 4. The possible score range is 0 to 4.


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Q11. responses for each of the eight items for BISF-W (nine items for BISF-M) are scored 
as (0) = 0/not applicable, (1) = 0/not applicable, (2)= 0, (3) = 1, (4) = 2, (5) = 3, (6) = 4. The 
final score for BISF_W and BISF_M is the sum of the item scores divided by 4 and 4.5 
respectively. The possible score range is 0 to 8. 
Q12. responses are scored as (0) = 0/not applicable, (1) = 4, (2) = 2, (3) = 0. The possible 
score range is 0 to 4. 
Q13. responses for each of the five items are scored as (0) = 0/not applicable, (1) = -2, (2) = 
-1, (3) = 0, (4) = 1, (5) = 2. The final score is the sum of the item scores. The possible score 
range is -10 to 10. This question measures change during the past month and does not 
contribute to any dimension. 
Q14. responses for each of the eight items for BISF-W (seven items for BISF-M) are scored 
as (0) = 0, (1) = 1, (2) = 2, (3) = 3, (4) = 4. The final score for BISF_W and BISF_M is the 
sum of the item scores divided by 8 and 7 respectively. The possible score range is 0 to 4. 
Q15. responses for each of the five items (including other, if specified) are scored as (0) = 
0/not applicable, (1)= 0, (2) = 1, (3) = 2, (4) = 3, (5) = 4. The final score is the sum of the 
item scores divided by 5. The possible score range is 0 to 4. 
Q16. responses are scored at (0) = 0, (1) = 1, (2) = 2, (3) = 3, (4) = 4. The possible score 
range is 0 to 4. 
Q17. responses are scored as (0) = 0/not applicable, (1)= 4, (2) = 3, (3) = 2, (4) = 1, (5) = 0. 
The possible score range is 0 to 4. 
Q18. responses are scored as (0) = 0/not applicable, (1) = 4, (2) = 3, (3) = 2, (4) = 1, (5) = 0. 
The possible score range is 0 to 4. 
Q19. responses are scored as (0) = 0/not applicable, (1) = 4, (2) = 3, (3) = 2, (4) = 1, (5) = 0. 
The possible score range is 0 to 4. 
Q20. responses are scored as (0) = 0, (1) = 1, (2) = 2, (3) = 3, (4) = 4. The possible score 
range is 0 to 4. 
Q21. responses are not scored. This question provides information on sexual orientation not 
pertinent to the scoring of any dimension. 
Q22. responses are not scored. This question provides information on sexual orientation not 
pertinent to the scoring of any dimension. 
 
Composite score 
 
The composite score will be calculated based on the seven dimension scores as: 
D1 + D2 + D3 + D4 + D5 + D6 – D7 
Here, D7 subtracted in the formular so that a higher composite scores represents greater 
sexual function. 
 
5.4        SAS code 
 
Paired t-test with multiplicity correction 
/* Perform paired t-test and output p-value on variable DIFF (paired 
difference of two variables of interest). Repeat for other differences */ 
proc ttest data=<dataset> sides=2 alpha=0.05 H0=0; 
var DIFF;


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ods output ttests=ttest_pvalue; 
run; 
 
/* Sort all p-values in ascending order */ 
proc sort data=ttest_pvalue out= allpvaluessorted; 
by probt; 
run; 
 
/* Do multiple adjustment on the sorted p-values using Hochberg procedure */ 
proc multtest pdata(probt)=allpvaluessorted hoc; 
run; 
 
 
Receiver Operating Characteristic curve and area under the curve 
/* The plots=<dataset>(id=prob) specification will display a ROC curve that 
will have certain points labeled with their predicted probabilities */ 
ods graphics on; 
proc logistic data=<dataset> plots=<dataset>(id=prob); 
model <response>(event='1') = <predictor>; 
roc '<predictor’s label>' <predictor>; 
run; 
ods graphics off; 
 
 
6          Reference 
 
Chularojanamontri L., Griffiths, C.E.M. and Chalmers J.G. (2013). ‘‘The Simplified Psoriasis 
Index (SPI): A Practical Tool for Assessing Psoriasis’’. Journal of Investigative Dermatology, 
133, 1956-1962 
 
DeLong, E. R., DeLong, D. M., and Clarke-Pearson, D. L. (1988). “Comparing the Areas 
under Two or More Correlated Receiver Operating Characteristic Curv es: A Nonparametric 
Approach”. Biometrics, 44, 837-845 
 
Mazer, N. A., Leiblum, S. R., & Rosen, R. C. (2000). ‘‘The brief index of sexual functioning 
for women (BISF-W): a new scoring algorithm and comparison of normative and surgically 
menopausal populations”. Menopause, 7(5), 350-363