Clinical trial NCT03504852
Conditions: Moderate to Severe Chronic Plaque-type Psoriasis
Keywords: psoriasis secukinumab immune-mediated systemic disease papules plaques itching weight
Sponsor: Novartis Pharmaceuticals
Start date: 2018-06-25; Completion date: 2020-07-15
Enrollment: 331 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess secukinumab high dose (every 2 weeks) vs standard dose (every 4 weeks) in heavy body weight subjects with moderate to severe plaque psoriasis.

Detailed description:
A 52-week multicenter, randomized, double-blind, parallel-group trial in 331 subjects with moderate to severe chronic plaque-type psoriasis of body weight 90 kg or higher at time of randomization.

This study consisted of 4 periods: screening (up to 4 weeks), treatment Period 1 (16 weeks), treatment Period 2 (36 weeks), and post-treatment follow-up (8 weeks).

Subjects were randomized using a 1:1 ratio to the following groups: Secukinumab 300 mg every 2 weeks; Secukinumab 300 mg every 4 weeks.

In addition, subjects from the 300 mg every 4 weeks group who did not achieve Psoriasis Area Severity Index (PASI) 90 response at Week 16 were reassigned using a 1:1 ratio to either remain on secukinumab 300 mg every 4 weeks or receive secukinumab 300 mg every 2 weeks starting at Week 16, until the end of treatment.

Arms: arm 1: 2 injections of secukinumab 150 mg once weekly up to week 4 and thereafter every 2 weeks. Subjects remained on secukinumab 300 mg every 2 weeks until the end of treatment. arm 2: 2 injections of secukinumab 150 mg once weekly up to week 4 and thereafter Q4W. Includes both subjects randomized to remain on Q4W the entire treatment period, and subjects that were Psoriasis Area and Severity Index (PASI) 90 responders at Week 16 from the secukinumab 300 mg Q4W possible up-titrate group. arm 3: 2 injections of secukinumab 150 mg once weekly up to week 4, then Q4W up to Week 16 and thereafter Q2W. Includes Psoriasis Area and Severity Index (PASI) 90 non-responders (NR) at Week 16 from the secukinumab 300 mg Q4W possible up-titrate group (subjects randomized to switch to Q2W if PASI 90 non-responder at Week 16).
Interventions: intervention 1: secukinumab 150 mg
Intervention descriptions: intervention 1: sub-cutaneous secukinumab prefilled syringe 150 mg

Protocol documents:
Prot_000.pdf: 
Global Clinical Development - General Medicine 
Secukinumab (AIN457)
Clinical Trial Protocol CAIN457A2324 / NCT03504852 
A randomized, double-blind, multicenter study assessing short 
(16 weeks) and long-term efficacy (up to 1 year), safety, and 
tolerability of sub-cutaneous secukinumab in subjects of body 
weight 90 kg or higher with moderate to severe chronic plaque-type 
psoriasis 
Document type:
Clinical Trial Protocol
EUDRACT number:
2015-004620-60
Version number:
00 (Original Protocol)
Clinical trial phase:
IIIB
Release date:
18-Dec-2017
Property of Novartis
Confidential
May not be used, divulged, published, or otherwise disclosed
without the consent of Novartis
Clinical Trial Protocol Template Version 3.2 (July 2016)


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Table of contents
Table of contents .................................................................................................................2
List of tables ........................................................................................................................5
List of figures ......................................................................................................................5
List of abbreviations............................................................................................................6
Glossary of terms.................................................................................................................8
Protocol summary..............................................................................................................10
1
Introduction .......................................................................................................................13
1.1
Background............................................................................................................13
1.2
Purpose ..................................................................................................................14
2
Study objectives and endpoints .........................................................................................14
2.1
Objectives and related endpoints...........................................................................14
3
Investigational plan ...........................................................................................................17
3.1
Study design...........................................................................................................17
3.2
Rationale for study design .....................................................................................19
3.3
Rationale for dose/regimen, route of administration and duration of treatment....20
3.4
Rationale for choice of comparator .......................................................................21
3.5
Purpose and timing of primary endpoint analysis/design adaptations...................21
3.6
Risks and benefits..................................................................................................21
4
Population..........................................................................................................................23
4.1
Inclusion criteria ....................................................................................................23
4.2
Exclusion criteria...................................................................................................24
5
Treatment...........................................................................................................................26
5.1
Study treatment......................................................................................................26
5.1.1
Investigational and control drugs..........................................................26
5.1.2
Additional treatment..............................................................................26
5.2
Treatment arms......................................................................................................26
5.3
Treatment assignment and randomization.............................................................27
5.4
Treatment blinding.................................................................................................27
5.4.1
Unblinding for primary endpoint analysis ............................................28
5.5
Treating the patient................................................................................................28
5.5.1
Patient numbering .................................................................................28
5.5.2
Dispensing the study drug.....................................................................28
5.5.3
Handling of study and additional treatment..........................................29
5.5.4
Instructions for prescribing and taking study treatment........................30
5.5.5
Permitted dose adjustments and interruptions of study treatment ........31


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5.5.6
Rescue medication ................................................................................31
5.5.7
Concomitant medication .......................................................................31
5.5.8
Prohibited medication ...........................................................................31
5.5.9
Emergency breaking of assigned treatment code..................................33
5.6
Study completion and discontinuation...................................................................34
5.6.1
Study completion and post-study treatment..........................................34
5.6.2
Discontinuation of study treatment .......................................................34
5.6.3
Withdrawal of informed consent...........................................................35
5.6.4
Loss to follow-up ..................................................................................36
5.6.5
Early study termination by the sponsor.................................................36
6
Visit schedule and assessments .........................................................................................36
6.1
Information to be collected on screening failures..................................................41
6.2
Patient demographics/other baseline characteristics .............................................41
6.2.1
Demographics .......................................................................................41
6.2.2
Psoriasis medical history / previous psoriasis therapies .......................41
6.2.3
Smoking history ....................................................................................41
6.2.4
Co-morbidities – cardiovascular medical history .................................41
6.2.5
Relevant medical history/current medical conditions...........................41
6.2.6
Determination of the tuberculosis status...............................................42
6.2.7
Other baseline characteristics................................................................44
6.3
Treatment exposure and compliance .....................................................................45
6.4
Efficacy..................................................................................................................45
6.4.1
Investigator Global Assessment (IGA mod 2011)................................45
6.4.2
Assessment of total Body surface Area and Psoriasis Area Severity 
Index......................................................................................................46
48
6.4.4
Appropriateness of efficacy assessments..............................................48
6.5
Safety.....................................................................................................................48
6.5.1
Physical examination ............................................................................49
6.5.2
Vital signs..............................................................................................49
6.5.3
Height and weight .................................................................................49
6.5.4
Laboratory evaluations..........................................................................50
6.5.5
Electrocardiogram (ECG) .....................................................................51
6.5.6
Pregnancy and assessments of fertility .................................................51
52
52


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53
53
54
7
Safety monitoring..............................................................................................................54
7.1
Adverse events.......................................................................................................54
7.2
Serious adverse events...........................................................................................56
7.2.1
Definition of SAE .................................................................................56
7.2.2
SAE reporting........................................................................................57
7.3
Liver safety monitoring .........................................................................................58
7.4
Reporting of study treatment errors including misuse/abuse ................................59
7.5
Pregnancy reporting...............................................................................................59
8
Data review and database management.............................................................................60
8.1
Site monitoring ......................................................................................................60
8.2
Data collection.......................................................................................................60
8.3
Database management and quality control............................................................61
8.4
Data Monitoring Committee..................................................................................61
8.5
Adjudication Committee........................................................................................62
9
Data analysis......................................................................................................................62
9.1
Analysis sets ..........................................................................................................62
9.2
Patient demographics and other baseline characteristics.......................................62
9.3
Treatments .............................................................................................................62
9.4
Analysis of the primary variable(s) .......................................................................63
9.4.1
Primary Variable(s)...............................................................................63
9.4.2
Statistical model, hypothesis, and method of analysis..........................63
9.4.3
Handling of missing values/censoring/discontinuations.......................64
9.4.4
Sensitivity analyses ...............................................................................64
9.5
Analysis of secondary variables ............................................................................64
9.5.1
Efficacy variables..................................................................................64
9.5.2
Safety variables .....................................................................................65
66
66
67
67
67
67


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9.7
Interim Analyses....................................................................................................68
9.8
Sample size calculation..........................................................................................69
10 Ethical considerations........................................................................................................69
10.1
Regulatory and ethical compliance........................................................................69
10.2
Informed consent procedures.................................................................................69
10.3
Responsibilities of the investigator and IRB/IEC..................................................70
10.4
Publication of study protocol and results...............................................................70
10.5
Quality Control and Quality Assurance.................................................................70
11 Protocol adherence ............................................................................................................71
11.1
Protocol amendments.............................................................................................71
12 References .........................................................................................................................71
13 Appendices ........................................................................................................................73
13.1
Appendix 1: Clinically notable laboratory values and vital signs .........................73
13.2
Appendix 2: Liver event and Laboratory trigger Definitions and Follow-up 
Requirements.........................................................................................................74
76
List of tables
Table 2-1
Objectives and related endpoints ..........................................................15
Table 3-1
Exposure to 300 mg s.c. every 2 weeks in completed trials .................22
Table 5-1
Prohibited medication ...........................................................................32
Table 6-1
Assessment schedule.............................................................................38
Table 6-2
The IGA mod 2011 rating scale............................................................45
Table 6-3
The PASI scoring system......................................................................46
Table 7-1 
Guidance for capturing the study treatment errors including 
misuse/abuse .........................................................................................59
Table 13-1
Liver Event and Laboratory Trigger Definitions ..................................74
Table 13-2
Follow-up Requirements for Liver Events and Laboratory Triggers....74
76
76
List of figures
Figure 3-1
Study design..........................................................................................17
Figure 3-2
Predicted systemic exposure with secukinumab 300 mg given 
every 2 weeks or every 4 weeks during maintenance ..........................20
Figure 6-1
Tuberculosis screening flowchart .........................................................44


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List of abbreviations
AE
Adverse Event
Alb
Albumin
ALT
Alanine Aminotransferase
ALP
Alkaline Phosphatase
AST
Aspartate Aminotransferase
ATC
Anatomical Therapeutic Chemical (ATC)
BDR
Bioanalytical Data Report
β-hCG
β-subunit of hCG gonadotropin
BSA
Body Surface Area
CD
Cluster of differentiation
CFR
US Code of Federal Regulations 
CHMP
Committee for medicinal products for human use
CRF
Case Report/Record Form (paper or electronic)
CRO
Contract Research Organization
CS
Corticosteroid
CT
Computerized tomography
ECG
Electrocardiogram
eCRF
Electronic Case Report Forms
EDC
Electronic Data Capture
e.g.
Exemplī grātiā (for example)
EOT
End of treatment
EU
European Union
FAS
Full analysis set
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GGT
Gamma-Glutamyl Transferase
hCG
Human chorionic gonadotropin
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Council for Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use
i.e.
of id est (in other words)
IEC
Independent Ethics Committee
IGA
Investigator’s Global Assessment
IGA mod
Investigator’s Global Assessment modified
IL
Interleukin


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i.v.
Intravenous
IRB
Institutional Review Board
IRT
Interactive Response Technology
LFT
Liver function test 
LLN
Lower Limit of Normal
MedDRA
Medical dictionary for regulatory activities 
MI
multiple imputation
MRI
Magnetic resonance imaging
PASI
Psoriasis Area and Severity Index
PEA
Primary endpoint analysis (PEA)
PFS
pre-filled syringes
Q2 / Q2W
Every 2 weeks
Q4 / Q4W
Every 4 weeks
QFT
QuantiFERON TB-Gold test
SAE
Serious Adverse Event
s.c.
subcutaneously
SGOT
Serum glutamic oxaloacetic transaminase
SGPT
Serum glutamic-pyruvic transaminase
TB
Tuberculosis
TBL
Total bilirubin
TNFα
Tumor necrosis factor alpha
USA
United States of America
UK
United Kingdom
ULN
Upper Limit of Normal
UV
Ultraviolet
WBC
White blood cells
WoCBP
Women of child bearing potential


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Glossary of terms
Cohort 
A specific group of patients/subjects fulfilling certain criteria
Control drug
Drugs(s) used as a comparator to reduce assessment bias, preserve blinding 
of investigational drug, assess internal study validity, and/or evaluate 
comparative effects of the investigational drug
Dosage
Dose of the study treatment given to the patient in a time unit (e.g. 100 mg
once a day, 75 mg twice a day)
Electronic Data 
Capture (EDC)
Electronic data capture (EDC) is the electronic acquisition of clinical study 
data using data collection systems, such as Web-based applications, 
interactive voice response systems and clinical laboratory interfaces.
EDC includes the use of Electronic Case Report Forms (eCRFs) which are 
used to capture data transcribed from paper source forms used at the point of 
care.
Enrollment
Point/time of subject entry into the study at which informed consent must be 
obtained (e.g. 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.”
Medication pack 
number
A unique identifier on the label of each investigational drug package
Part 
A single component of a study which contains different objectives or 
populations within that single study. Common parts within a study are: a 
single dose part and a multiple dose part, or a part in subjects with 
established disease and in those with newly-diagnosed disease.
PASI 90 response
Subjects achieving ≥ 90% improvement (reduction) in PASI score compared 
to baseline
Patient/subject ID 
A unique number assigned to each subject upon signing the informed 
consent 
Period
The subdivisions of the trial design (e.g. Screening, Treatment, Follow-up) 
which are described in the Protocol. Periods define the study phases and will 
be used in clinical trial database setup and eventually in analysis
Randomization 
number
A unique identifier assigned to each randomized subject, corresponding to a 
specific treatment arm assignment
Source 
Data/Document
Source data refers to the initial record, document, or primary location from 
where data comes. The data source can be a database, a dataset, a 


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spreadsheet or even hard-coded data.
Study drug/ treatment
Any single drug or combination of drugs administered to the subject as part of 
the required study procedures; includes investigational drug (s), 
placebo/comparator active drug run-ins or background therapy
Study Treatment 
Discontinuation
When the subject permanently stops taking study treatment prior to the 
defined study treatment completion date 
Variable
A measured value or assessed response that is determined in specific 
assessments and used in data analysis to evaluate the drug being tested in 
the study
Withdrawal of study 
consent
Withdrawal of consent from the study is defined as when a subject does not 
want to participate in the study any longer, and does not want any further 
visits or assessments, and does not want any further study related contact, 
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Protocol summary
Protocol number
CAIN457A2324
Full Title
A randomized, double-blind, multicenter study assessing short (16 weeks) 
and long-term efficacy (up to 1 year), safety, and tolerability of 
sub-cutaneous secukinumab in subjects of body weight 90 kg or higher 
with moderate to severe chronic plaque-type psoriasis
Brief title
Study of efficacy and safety of 2 secukinumab dose regimens in subjects of 
body weight 90 kg or higher with moderate to severe chronic plaque-type 
psoriasis
Sponsor and Clinical 
Phase
Novartis, Phase 3B
Investigation type
Drug
Study type
Interventional
Purpose and rationale
The purpose of this study is to compare efficacy, safety and tolerability of 
secukinumab 300 mg every 2 weeks to secukinumab 300 mg every 
4 weeks in subjects with moderate to severe chronic plaque-type psoriasis 
and body weight of 90 kg or higher. 
This study addresses a post-marketing commitment to the FDA (USA).
Primary Objective(s) 
To demonstrate the efficacy of secukinumab 300 mg every 2 weeks in 
comparison to secukinumab 300 mg every 4 weeks with respect to PASI 90 
response at Week 16
Secondary Objectives
To demonstrate the efficacy of secukinumab 300 mg every 2 weeks in 
comparison to secukinumab 300 mg every 4 weeks with respect to
Investigator’s Global Assessment (IGA) mod 2011 0 or 1 response at 
Week 16.
To investigate the clinical safety and tolerability of secukinumab 300 mg
every 2 weeks in comparison to secukinumab 300 mg every 4 weeks
Study design
This is a 52-week multicenter, randomized, double-blind, parallel-group trial 
in approximately 330 subjects with moderate to severe chronic plaque-type 
psoriasis of body weight 90 kg or higher at time of randomization.
The study consists of 4 periods: screening (up to 4 weeks), treatment 
Period 1 (16 weeks), treatment Period 2 (36 weeks), and post-treatment 
follow-up (8 weeks). 
Subjects will be randomized using a 1:1 ratio to the following groups: 
Secukinumab 300 mg
every 2 weeks; Secukinumab 300 mg
every 
4 weeks. 
 
 
 
 
Population
The study population will consist of approximately 330 adult male and 
female subjects (≥ 18 years old) with moderate to severe chronic plaque-


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type psoriasis of body weight of ≥ 90 kg at randomization.
Key Inclusion criteria
1.
Written informed consent must be obtained before any assessment is 
performed. Where relevant, a legal representative will also sign the 
informed study consent according to local laws and regulations.
2.
Subjects must be able to understand and communicate with the 
investigator and comply with the requirements of the study.
3.
Men or women at least 18 years of age at time of screening.
4.
Body weight of ≥90 kg at the time of randomization.
5.
Chronic plaque-type psoriasis present for at least 6 months and 
diagnosed before randomization.
6.
Moderate to severe psoriasis as defined at randomization by:

Psoriasis Area and Severity Index (PASI) score of 12 or greater, 
and

IGA mod 2011 score of 3 or greater (based on a static scale of 0 –
4), and

Body Surface Area (BSA) affected by plaque-type psoriasis of 10% 
or greater.
7.
Candidate for systemic therapy. This is defined as a subject having 
moderate to severe chronic plaque-type psoriasis that is inadequately 
controlled by:

topical treatment and/or,

phototherapy and/or,

previous systemic therapy.
Key Exclusion criteria
1.
Forms of psoriasis other than chronic plaque-type (e.g., pustular, 
erythrodermic and guttate psoriasis) at screening or Randomization.
2.
Ongoing use of prohibited treatments. Washout periods detailed in the 
protocol have to be adhered to (Table 5-1). Subjects not willing to limit 
UV light exposure (e.g., sunbathing and / or the use of tanning devices) 
during the course of the study will be considered not eligible for this 
study since UV light exposure is prohibited. Note: administration of live 
vaccines 6 weeks prior to Randomization or during the study period is 
also prohibited. 
3.
Previous exposure to secukinumab (AIN457) or any other biologic drug 
directly targeting Interleukin-17 (IL-17) or the IL-17 receptor.
4.
Use of other investigational drugs at the time of enrollment, or within 5 
half-lives of enrollment, or within 4 weeks
until the expected 
pharmacodynamic effect has returned to baseline, whichever is longer; 
or longer if required by local regulations.
5.
Pregnant or nursing (lactating) women
6.
History of lymphoproliferative disease or any known malignancy or 
history of malignancy of any organ system treated or untreated within 
the past 5 years, regardless of whether there is evidence of local 
recurrence or metastases (except for skin Bowen’s disease, or basal 
cell carcinoma or actinic keratoses that have been treated with no 


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evidence of recurrence in the past 12 weeks; carcinoma in situ of the 
cervix or non-invasive malignant colon polyps that have been 
removed).
7.
History of hypersensitivity to any of the study drug constituents.
Study treatment

Secukinumab 150 mg solution for sub-cutaneous injection in a 1 ml 
pre-filled syringe

Placebo solution for sub-cutaneous injection in a 1 ml pre-filled syringe
Efficacy assessments

Investigator’s Global Assessment for general psoriasis (IGA mod 2011; 
scale from 0 – 4)

Psoriasis Area and Severity Index (PASI; score from 0 – 72)
 
Key 
safety 
assessments

Evaluation of all AEs and SAEs

Physical examination

Vital signs

Height and weight

ECG

Laboratory evaluations (e.g. hematology, clinical chemistry, urinalysis)

Pregnancy
 
Data analysis
The hypotheses will be tested sequentially and are included in a 
hierarchical testing strategy. Type-I-errors are set to keep a family-wise 
type-I-error of 2.5% (one-sided):
H1:
secukinumab 300 mg
every 2 weeks is not superior
to 
secukinumab 300 mg every 4 weeks with respect to PASI 90 response at 
Week 16.
H2:
secukinumab 300 mg
every 2 weeks
is not superior
to 
secukinumab 300 mg every 4 weeks with respect to IGA mod 2011 0 or 1
response at Week 16.
The testing sequence will continue to H2 at α (one-sided) only if H1 has 
been rejected.
The primary analysis method will be the logistic regression with treatment 
group, and baseline weight, baseline PASI score as explanatory variables. 
Odds ratios will be computed for comparisons between treatment arms
utilizing the logistic regression model fitted. In case of response rates of 0% 
or of 100% in one of the treatment groups, Fisher’s exact test will be 
applied. Confidence intervals for risk difference will be provided. Multiple 
imputation method will be used for handling missing data.
Key words
psoriasis, PASI, IGA mod 2011, secukinumab, pre-filled syringes


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1
Introduction
1.1
Background 
Psoriasis is a chronic relapsing disease of the skin characterized by variable clinical features. 
The lesions are classified as erythrosquamous, which indicates that both the vasculature 
(erythema) and the epidermis (increased scale formation) are involved. 
Plaque-type psoriasis (also called plaque or chronic plaque psoriasis) is the most frequent 
clinical presentation and therefore, also called psoriasis vulgaris. The erythematous plaques 
are well defined with sharp borders. The silvery grey scale on the surface of the lesions is 
easily removed. Sharply demarcated lesions can present on the extensor surfaces of the knees 
and elbows and on the trunk. Lesions are often symmetrically distributed. The size of the 
lesions is highly variable. Psoriasis may also occur on the scalp, palms and/or soles 
(palmoplantar psoriasis), nails and in skin folds (intertrigo psoriasis). The amount of psoriasis 
covering the body can be measured roughly as a percentage of body surface area, using the 
handprint to represent 1% of the body surface. In approximately one-third of patients, more 
than 10% of the body is covered, and this is termed moderate to severe psoriasis. Clinical 
disease can also be assessed by a trained health-care practitioner, using the Psoriasis Area and 
Severity Index (PASI) score. This tool ranks severity of erythema (redness), induration 
(thickness), and desquamation (scale) and area affected by the plaques in different body 
sections, with 72 as the maximal score. PASI score of at least 12 is usually required to classify 
for moderate to severe psoriasis.
Treatment of moderate to severe psoriasis was based on phototherapy, conventional systemic 
treatment (e.g. methotrexate, cyclosporine, acitretin) and biologics (tumor necrosis factor 
alpha (TNFα)-inhibitors etanercept, infliximab and adalimumab).The primary indication for 
these biological products is the treatment of moderate to severe psoriasis not responding 
satisfactorily to phototherapy and conventional systemic treatment such as methotrexate or 
acitretin.
Extensive clinical experience with TNFα-inhibitors has been collected over the past 10 years 
and these agents are generally considered to be effective and relatively safe (Papp et al 2006). 
However, a substantial percentage of patients do not respond well to treatment with TNFα-
inhibitors. This inadequate response may imply either a primary failure (e.g. not achieving a 
decrease in Psoriasis Area and Severity Index (PASI) score of at least 50% after adequate 
duration of treatment), secondary failure (an initially adequate response that is lost over time) 
or intolerance for the TNFα-inhibitor. The percentage of patients with an inadequate response 
to TNFα-inhibitors can be as high as 40 to 60% (van Lümig et al 2010).
The arrival of a new class of systemic, biological drugs such as ustekinumab (interleukin (IL)-
12/23 inhibitor) has provided clinicians with more treatment options. Ustekinumab has shown 
good clinical efficacy in a number of well-designed Phase 3 studies (Papp et al 2008). PASI 
response rates were better than those of etanercept and comparable to PASI response rates of 
infliximab and efficacy was generally maintained up to 3 years after initiation of treatment 
(Kimball et al 2012). Additionally, a number of IL-17A and IL-17RA inhibitors are 
investigated for the treatment of a range of immune mediated inflammatory diseases. 


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Secukinumab (AIN457) is a recombinant high-affinity fully human monoclonal anti-human 
IL-17A antibody of the immunoglobulin (Ig) G1/κ-class. Secukinumab binds to human 
IL-17A and neutralizes the bioactivity of this cytokine. IL-17A is the central cytokine of a 
newly defined subset of inflammatory T cells, the Th17 cells which, in several animal models, 
are pivotal in multiple autoimmune and inflammatory processes. IL-17A is mainly produced 
by memory effector CD4+ and CD8+ T lymphocytes and is being recognized as one of the 
principal pro-inflammatory cytokines in immune mediated inflammatory diseases. Its 
neutralization is expected to treat the underlying pathophysiology of immune mediated 
disease, and as a consequence provide relief of psoriatic symptoms. Secukinumab has been 
shown to be superior to etanercept (Langley et al 2014) and superior to ustekinumab 
(Thaci et al 2015) in clearing skin of subjects with moderate to severe psoriasis with 
comparable safety profile.
Secukinumab (Cosentyx®) was approved in 2014 in Japan, in 2015 in the US (FDA 2014), in 
the European Union (EU), in Switzerland and in other countries for the treatment of moderate 
to severe plaque psoriasis in adults, with a recommended dose of 300 mg by subcutaneous 
injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing 
starting at Week 4. Secukinumab is available as a powder for solution for injection, and as a 
solution of 150 mg in 1 mL for injection in pre-filled syringe or pre-filled pen. Currently two 
injections are required for the administration of the recommended dose.
As of 25 Jun 2017, over 11,000 subjects (healthy subjects and patients) have received 
secukinumab in Novartis sponsored clinical studies at doses ranging from 0.1 mg/kg to 
30 mg/kg intravenously (i.v.), and from 25 mg to 300 mg subcutaneously (s.c.), given as 
single or multiple doses. Full safety results including all reported AEs are currently available 
for completed studies across different indications. In general, these results show comparable 
numbers of adverse events (AEs) in subjects treated with secukinumab compared to placebo 
without indication of any specific organ toxicity. The Investigator’s Brochure (IB) provides a 
more detailed review of the pre-clinical and clinical information on secukinumab.
1.2
Purpose 
The purpose of this study is to compare efficacy, safety and tolerability of secukinumab 
300 mg every 2 weeks to secukinumab 300 mg every 4 weeks in subjects with moderate to 
severe chronic plaque-type psoriasis and body weight of 90 kg or higher, 
 
 
This study addresses a post-marketing commitment to the FDA (USA). Refer to Section 3.2
for detail on commitment. 
2
Study objectives and endpoints
2.1
Objectives and related endpoints
The objectives and related endpoints presented in Table 2-1 will be evaluated in subjects with 
body weight of 90 kg or higher at randomization and with moderate to severe chronic plaque-
type psoriasis.


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Table 2-1
Objectives and related endpoints
Objective(s)
Endpoint(s)
Primary Objective(s)
Endpoint(s) for primary objective(s) 
To demonstrate the efficacy of secukinumab 
300 mg every 2 weeks in comparison to 
secukinumab 300 mg every 4 weeks with 
respect to PASI 90 response at Week 16
Endpoint: PASI 90 response 
Description: Percentage of subjects who 
achieve ≥ 90% reduction in PASI score 
compared to baseline 
Time frame: 16 weeks
Secondary Objective(s)
Endpoint(s) for secondary objective(s)
To demonstrate the efficacy of secukinumab 
300 mg every 2 weeks in comparison to 
secukinumab 300 mg every 4 weeks with 
respect to Investigator’s Global Assessment 
(IGA) mod 2011 0 or 1 response at 
Week 16.
Endpoint: IGA mod 2011 0 or 1 response 
Description: Percentage of subjects who 
achieve IGA mod 2011 0 or 1 and improved 
by at least 2 points on the IGA scale 
compared to baseline.
Time frame: 16 weeks
To investigate the clinical safety and 
tolerability of secukinumab 300 mg every 2 
weeks in comparison to secukinumab 
300 mg every 4 weeks
Endpoint: Clinical safety and tolerability.
Measure: vital signs, clinical laboratory 
variables, ECGs, Adverse Events monitoring
Time frame: up to 52 weeks


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3
Investigational plan
3.1
Study design
This is a 52-week multicenter, randomized, double-blind, parallel-group trial in approximately 
330 subjects with moderate to severe chronic plaque-type psoriasis of body weight 90 kg or 
higher at time of randomization.
The study consists of 4 periods: screening (up to 4 weeks), treatment Period 1 (16 weeks), 
treatment Period 2 (36 weeks), and follow-up (8 weeks). 
Safety, efficacy, 
 of 
secukinumab will be performed. 
An outline of the study design is presented in Figure 3-1 and a detailed visit and assessment 
schedule in Table 6-1.
Figure 3-1
Study design 
EOT1/2: End of treatment 1/2
     Q2Wks/Q4Wks: Every 2/4 weeks
Screening Period (Screening to Randomization)
The screening period of at least 1 week and up to 4 weeks will be used to assess the subject’s 
eligibility and to taper subjects off prohibited medications. 


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Treatment Period 1 (Randomization to Week 16 pre-dose)
The Treatment Period 1 is the period from randomization (baseline) through Week 16 prior to 
dosing. At the start of treatment Period 1, eligible subjects will be randomized via Interactive 
Response Technology (IRT) using a 1:1 ratio to one of the following treatment groups:

Secukinumab 300 mg every 2 weeks 

Secukinumab 300 mg every 4 weeks
Refer to Section 5.2 for details on treatment arms. 
All subjects will receive 2 injections of secukinumab 150 mg once weekly for four weeks (at 
Randomization, weeks 1, 2 and 3). Thereafter the frequency of secukinumab/placebo 
injections will be as per the treatment groups assigned at baseline. To maintain the treatment 
blind, subjects assigned to receive secukinumab 300 mg every 4 weeks will also receive two 
placebo injections (2 x secukinumab placebo 150 mg s.c.) every 4 weeks starting at Week 6
(see Figure 3-1).
Subjects who complete treatment Period 1 will enter treatment Period 2. For all subjects who 
discontinue 
study 
treatment 
prematurely 
for 
any 
reason 
before 
the 
End of Treatment Period 1/Week 16 visit (EOT 1), an EOT 1 visit should be performed 
approximately four weeks after their last dose of study drug and then subjects should enter the 
treatment free follow-up period. 
Treatment Period 2 (Week 16 post-dose to Week 52)
Treatment Period 2 is the period from Week 16 through Week 52. The Week 16 dose is the 
first dose of the treatment Period 2 and the last dose will be administered at Week 48. 

Subjects from the 300 mg every 2 weeks group will remain on secukinumab 300 mg every 
2 weeks until the end of treatment

Subjects from the 300 mg every 4 weeks group: 
 
 
 
This allocation will be based on a pre-assignment done at the randomization/baseline 
visit.
The planned end of treatment period 2 visit (EOT 2) will be performed at Week 52. 
For all subjects who discontinue study treatment prematurely for any reason before the end of 
treatment period 2/Week 52 (EOT2), an EOT2 visit should be performed approximately 
4 weeks after their last dose of study drug and then subjects should enter the post treatment 
follow-up period.


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Post treatment follow-up period
All subjects should enter the post treatment follow-up period, which includes the F4 and F8 
follow-up visits. No study treatment (secukinumab) is administered during this period. 
Follow-up visit F4 is approximately 4 weeks after the EOT 1/EOT 2 visit and 8 weeks after 
last study treatment administration. Follow-up visit F8 is approximately 8 weeks after the 
EOT 1/EOT 2 visit, and 12 weeks after the last study treatment administration. 
3.2
Rationale for study design
The patient population will be described in more detail in Section 4 below.
This study is a post approval commitment to the United States Food and Drug Administration 
(FDA). The FDA requested a clinical trial to:

evaluate the treatment effect and safety profile of a higher exposure of secukinumab in 
psoriasis subjects with higher body weight and 
 
The request was based on the FDA’s exposure-response analysis which suggested that IGA 
0/1 response rate in subjects with body weight ≥ 90 kg administered 300 mg may be further 
increased if exposures are increased 
 
The randomized, double-blind, parallel-group design of this study is aligned with previous 
studies performed in the indication of plaque psoriasis and registration secukinumab studies.
The blinding will be maintained throughout the study to ensure reliable efficacy and safety 
measures of the 300 mg every 2 weeks regimen and its comparison to the 300 mg every 
4 weeks regimen.
The primary endpoint 
 is PASI 90 assessed at Week 16. PASI 90 
was chosen as the primary efficacy variable to represent the therapeutic goal recognized by 
the American Academy of Dermatology and European Medicines Agency as “measure of 
optimal response” or “treatment success”. By Week 16 subjects would have the greatest 
chance of reaching maximum efficacy with secukinumab therapy, as established in the 
registration Phase 3 studies (PASI 90 response was around 70%). 
 
 
 
 
 
The study’s design, with a total treatment duration of 52 weeks, will allow assessment of long 
term efficacy and safety of the two dose regimens and is aligned with previous studies 
performed in the indication of plaque psoriasis and registration secukinumab studies.


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3.3
Rationale for dose/regimen, route of administration and duration 
of treatment
Secukinumab 300 mg s.c. with an initial weekly induction schedule up to 4 weeks followed 
by a s.c administration of every four weeks up to Week 48 is based on the secukinumab Phase
3 registration program.
A higher monthly dose regimen than the one approved for the psoriasis indication has been 
included in the study as requested by FDA. This higher monthly dose regimen is being 
assessed to see if improvement in response is achievable in subjects with body weight ≥90 kg, 
while maintaining a favorable safety profile.
Systemic exposure varies with body weight in an allometric relationship. For clearance, the 
allometric exponent was estimated to be close to 1; in other words, a doubling of body weight 
could lead to a nearly 2-fold increase in clearance and therefore reduced serum exposure 
(Bruin et al 2017). Therefore, evaluation of a dosing regimen with higher exposure than 
resulting from the marketed regimen is appropriate in this heavier subject population.
Based on a large database of Phase
II and Phase
III double-blind randomized 
placebo-controlled studies including 1,405 subjects treated with secukinumab, a clear 
dose/exposure response relationship was established. Serum secukinumab concentration was 
by far the most important predictor of efficacy. 
As shown in Figure 3-2, which presents predicted secukinumab concentration based on 
population pharmacokinetics models in psoriasis, shows that increasing the dose regimen 
from 300 mg every 4 weeks to 300 mg every 2 weeks after the induction period would result 
in a sustained higher secukinumab serum concentration.
Figure 3-2
Predicted systemic exposure with secukinumab 300 mg given every 2 
weeks or every 4 weeks during maintenance
300 mg Q4: secukinumab 300 mg weekly for 5 weeks (induction), then every 4 weeks (maintenance)
300 mg Q2: secukinumab 300 mg weekly for 5 weeks (induction), then every 2 weeks (maintenance)


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Therefore the hypothesis to be tested in this study is that increasing the exposure to 
secukinumab in subjects with higher weight (i.e. ≥ 90 kg) would result in higher percentage of 
subjects achieving PASI 90 at Week 16.
Risk benefit evaluation of the proposed doses are presented in Section 3.6, Risk and benefits.
3.4
Rationale for choice of comparator
This study will compare a higher dose regimen (i.e. 300 mg every 2 weeks) which could 
potentially bring improvement in response while maintaining a favorable safety profile versus 
secukinumab 300 every 4 weeks, which is the approved dose regimen for psoriasis patients. 
3.5
Purpose and timing of primary endpoint analysis/design 
adaptations
A primary endpoint analysis (PEA) may be conducted when all subjects have completed the 
Week 16 visit at which the primary endpoint is assessed. Additional analyses may be 
performed to support health authority interactions as necessary.
3.6
Risks and benefits 
Secukinumab (Cosentyx) with a recommended dose of 300 mg every 4 weeks was approved 
in 2014 in Japan, in 2015 in the US, in the EU, in Switzerland and other countries for the 
treatment of adults with moderate to severe plaque psoriasis. Secukinumab 150 mg is 
available as a powder for solution for injection, and as a solution for injection in pre-filled 
syringe or pre-filled pen.
Non-clinical studies and Phase 2 and 3 clinical studies in adults have not shown any 
impediment to using secukinumab subcutaneously in human. As of 25 Jun 2017, over 11,000 
patients and healthy volunteers received secukinumab treatment in Novartis sponsored 
investigational clinical studies, including approximately 5,865 patients with moderate to 
severe plaque psoriasis. 
In adult studies, secukinumab has shown an excellent efficacy profile in the treatment of 
moderate to severe chronic plaque psoriasis. Superiority of secukinumab 300 mg to placebo 
was demonstrated for the co-primary efficacy criteria of PASI 75 and IGA mod 2011 0 or 1 at 
12 weeks in all 4 pivotal placebo-controlled trials (> 62% for PASI 75 and > 48% for IGA 
mod 2011 0 or 1). Etanercept and placebo-controlled Studies CAIN457A2302 and 
CAIN457A2303 have shown the superior efficacy of secukinumab 300 mg compared to 
etanercept and placebo with a rapid onset of action, while Study CAIN457A2317 showed 
superiority and sustained long-term efficacy of secukinumab 300 mg versus ustekinumab in 
patients with moderate to severe plaque-type psoriasis.
Potential risks for subjects are as outlined in the approved product labelling. At this time, 
safety data including (1) AE data, laboratory parameters, available immunogenicity data from 
the completed studies, and (2) SAE data from the Phase 3 studies do not show any other 
safety risk apart from the approved safety profile. The safety data from the completed and 
ongoing studies demonstrate a good safety profile which includes an observed risk of 
infections in particular candida infections and neutropenia or hypersensitivity reactions that 
can be seen with administration of foreign proteins. Most of the infections were non-serious, 


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mild to moderate in severity, clinically easily manageable and did not lead to treatment 
discontinuation. Cases of neutropenia were uncommon, generally mild to moderate and 
transient and did not lead to treatment discontinuation, and only a few cases were temporally 
associated with non-serious infections.
Subjects with pre-existing malignancies within the past 5 years are generally excluded from 
studies with secukinumab although no signals have been observed that would suggest that 
secukinumab would increase the risk for malignancies. 
Based upon the results of the toxicology studies demonstrating lack of effect of secukinumab 
on fertility and embryo-fetal development, women of child bearing potential (WoCBP) can be 
included in studies with secukinumab, but pregnancy should be avoided by proven effective 
measures. No contraceptive measures are required for males participating in studies with 
secukinumab.
Secukinumab 300 mg s.c. every 2 weeks was administered in 5 completed studies. For two of 
these studies (CAIN457C2302 and CAIN457A2208) the number of subjects was low (<10) 
and therefore these are not further discussed here.
Patients with uveitis received secukinumab 300 mg s.c. every 2 weeks for up to 50 weeks in 
Study CAIN457C2301/C2301E1 and up to 44 weeks in Study CAIN457C2303/2303E1.
Table 3-1
Exposure to 300 mg s.c. every 2 weeks in completed trials
Study (Indication)
Average weight (kg) 
Number of subjects exposed for:
Any duration
6 months
1 year
CAIN457C2301& 
CAIN457C2301E1 (Uveitis)
79.4
29
21
4
CAIN457C2303& 
CAIN457C2303E1 (Uveitis)
69.8
39
34
0
In Study CAIN457C2301/C2301E1, the overall number of subjects with an adverse event was 
similar between subjects who received secukinumab 300 mg every 2 weeks versus those who 
received placebo at the same frequency (82.8% versus 84.8% respectively), while in Study
CAIN457C2303/2303E1, the overall frequency of AE was higher in the secukinumab 300 mg
every 2 weeks group compared to placebo (82.1% versus 74.4% respectively). Long-term 
treatment with more frequent s.c. doses of secukinumab (300 mg every 2 weeks) was 
associated with a numerical increase in infections, mainly due to more reports of non-serious 
nasopharyngitis, influenza, and upper respiratory tract infection in both studies. The sample 
size for the secukinumab 300 mg every 2 weeks were relatively small in these studies and 
interpretation of these results must therefore be done with caution.
Secukinumab 300 mg s.c. every 2 weeks was also administered in one ongoing study for 
which the results are available. Study CAIN457ADE04 is a randomized, double blind, 
multicenter study to assess the efficacy and safety of 16 weeks secukinumab dosage interval 
shortening (2 weekly 300 mg s.c.) in comparison to continued standard treatment (4 weekly 
300 mg s.c.) in patients with moderate severe plaque type psoriasis who achieved less than 
clear or almost clear skin (PASI response greater than or equal to 75 to PASI less than 90) 
after 16 weeks under the standard dose of secukinumab. A total of 772 subjects were enrolled 


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into the selection phase of the study, then 325 subjects were randomized to either 
secukinumab every 4 weeks (N=162) or every 2 weeks (N=163). 
Within the randomized subjects, there was a lower incidence rate of AEs in the 300 every 2 
weeks arm compared to the 300 mg every 4 weeks arm (12.9% and 16.7%, respectively). The 
majority of the AEs were from the SOC infections and infestations (10.5%), with mild or 
moderate nasopharyngitis as the primary contributor (3.1%). An increase in candida infection 
rate was observed in the 300 mg every 2 weeks arm (3.1%) as compared to the 300 mg every 
4 weeks arm (1.2%). Serious adverse events occurred at comparable rates to other 
secukinumab studies. SAEs occurred less frequently in the 300 mg every 2 weeks arm, and 
were also less often related in this arm than in the 300 mg every 4 weeks arm (2.5% and 4.9%, 
respectively). The most common SOC was infections and infestations (1.2%); 4 of the 5 
reported serious infections were assessed as related to study treatment. AEs and SAEs lead to 
permanent discontinuation of study treatment in the 300 mg every 4 weeks only (0.9%), and 
to interruption of study treatment less frequently in the 300 mg every 2 weeks arm than in the 
300 mg every 4 weeks arm (0.6% and 2.5%, respectively). Results from this study showed no 
unexpected safety signals in the safety profile of secukinumab at both doses regimens. 
4
Population
The study population will consist of a representative group of adult male and female subjects 
(≥ 18 years old) with moderate to severe chronic plaque-type psoriasis of body weight of
≥90 kg at randomization. It is aimed to randomize a total of approximately 330 subjects in 
approximately 100 study sites worldwide. Approximately 472 subjects (30% projected screen 
failure rate) are expected to be screened to provide the number of randomized subjects. 
Subjects who drop out after they have been randomized will not be replaced.
4.1
Inclusion criteria
Subjects eligible for inclusion in this study must fulfill all of the following criteria:
1. Written informed consent must be obtained before any assessment is performed. Where 
relevant, a legal representative will also sign the informed study consent according to 
local laws and regulations.
2. Subjects must be able to understand and communicate with the investigator and comply 
with the requirements of the study.
3. Men or women at least 18 years of age at time of screening.
4. Body weight of ≥90 kg at the time of randomization.
5. Chronic plaque-type psoriasis present for at least 6 months and diagnosed before 
randomization.
6. Moderate to severe psoriasis as defined at randomization by:

PASI score of 12 or greater, and

IGA mod 2011 score of 3 or greater (based on a static scale of 0 – 4), and

Body Surface Area affected by plaque-type psoriasis of 10% or greater.
7. Candidate for systemic therapy. This is defined as a subject having moderate to severe 
chronic plaque-type psoriasis that is inadequately controlled by:


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
topical treatment and/or,

phototherapy and/or,

previous systemic therapy.
4.2
Exclusion criteria
Subjects fulfilling any of the following criteria are not eligible for inclusion in this study. No 
additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible subjects.
1. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of 
enrollment, or within 4 weeks until the expected pharmacodynamic effect has returned to 
baseline, whichever is longer; or longer if required by local regulations.
2. History of hypersensitivity to any of the study drug constituents.
3. Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and 
guttate psoriasis) at screening or Randomization.
4. Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, 
calcium channel inhibitors or lithium) at Randomization.
5. Ongoing use of prohibited treatments. Washout periods detailed in the protocol have to be 
adhered to (Table 5-1). Subjects not willing to limit UV light exposure (e.g., sunbathing 
and / or the use of tanning devices) during the course of the study will be considered not 
eligible for this study since UV light exposure is prohibited.
Note: administration of live vaccines 6 weeks prior to Randomization or during the study 
period is also prohibited. 
6. Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting 
IL-17 or the IL-17 receptor.
7. Pregnant or nursing (lactating) women
8. Women of child-bearing potential (WoCBP), defined as all women physiologically 
capable of becoming pregnant, unless they are using basic methods of contraception 
during the entire study or longer if required by locally approved prescribing information 
(e.g. in EU 20 weeks).
Basic 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], total hysterectomy or tubal ligation at least six weeks before taking study 
treatment). In case of oophorectomy alone, only when the reproductive status of the 
woman has been confirmed by follow-up hormone level assessment.

Male sterilization (at least 6 months prior to screening). The vasectomized male partner 
should be the sole partner for that subject.

Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault 
caps). For United Kingdom: with spermicidal foam/gel/film/cream/vaginal suppository. 


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
Use of oral (estrogen and progesterone), injected or implanted hormonal methods of
contraception or other forms of hormonal contraception that have comparable efficacy
(failure rate <1%), for example hormone vaginal ring or transdermal hormone
contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS).
In case of use of oral contraception women should have been stable on the same pill for a
minimum of 3 months before taking study treatment.
In case local regulations deviate from the contraception methods listed above, local
regulations apply and will be described in the informed consent form (ICF).
Note: Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical
profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical
bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal
ligation at least six weeks ago. In the case of oophorectomy alone, only when the
reproductive status of the woman has been confirmed by follow-up hormone level
assessment is she considered not of child bearing potential.
9. Active ongoing inflammatory diseases other than psoriasis that might confound the
evaluation of the benefit of secukinumab therapy. Also, underlying conditions (including,
but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic,
endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator
significantly immunocompromises the subject and/or places the subject at unacceptable
risk for receiving an immunomodulatory therapy. In addition, current severe progressive
or uncontrolled diseases which renders the subject unsuitable for the trial or puts the
subject at increased risk, including any medical or psychiatric condition which, in the
Investigator’s opinion, would preclude the participant from adhering to the protocol or
completing the study per protocol.
10. Presence of investigator identified significant medical problems which at investigator's
discretion will prevent the subject from participating the study, including but not limited
to the following:

Subjects with severely reduced kidney function (estimated glomerular filtration rate
(eGFR) ≤29 ml/min/1.73m2)
11. 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 randomization, and evaluated by a qualified physician.
12. Active systemic infections during the last two weeks (exception: common cold) prior to
randomization or any infection that reoccurs on a regular basis.
13. History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis
infection as defined by a positive QuantiFERON TB-Gold test (QFT) at screening.
Subjects with a positive or indeterminate QFT test may participate in the study if full
tuberculosis work up (according to local practice/guidelines) was completed within 12
weeks prior to randomization and establishes conclusively that the subject has no evidence
of active tuberculosis. If presence of latent tuberculosis is established, then treatment must
have been initiated and maintained according to local guidelines prior to randomization.


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14. Past medical history record of infection with human immunodeficiency virus (HIV), 
hepatitis B or hepatitis C prior to Randomization.
15. History of lymphoproliferative disease or any known malignancy or history of malignancy 
of any organ system treated or untreated within the past 5 years, regardless of whether 
there is evidence of local recurrence or metastases (except for 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).
16. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor 
tolerability or lack of access to veins). 
17. History or evidence of ongoing alcohol or drug abuse, within the last six months before 
Randomization.
5
Treatment
5.1
Study treatment
5.1.1
Investigational and control drugs
Novartis will supply the investigational therapy as follows: 

Secukinumab 150 mg solution for sub-cutaneous injection in a 1 ml pre-filled syringe

Placebo solution for sub-cutaneous injection in a 1 ml pre-filled syringe
Each Secukinumab placebo pre-filled syringe contains a mixture of inactive excipients, 
matching the composition and the appearance of the secukinumab 150 mg dose.
5.1.2
Additional treatment
No additional treatment beyond investigational drug and control drug are included in this trial.
5.2
Treatment arms
At Baseline/Randomization visit, all eligible subjects will be randomized via Interactive 
Response Technology (IRT) using a 1:1 ratio to one of the treatment groups:

Secukinumab 300 mg every 2 weeks group: subjects will receive 2 injections of 
secukinumab 150 mg once weekly for four weeks (at Randomization, Weeks 1, 2, and 3), 
followed by 2 injections of secukinumab 150 mg every two weeks, starting at Week 4 and 
up to Week 48.

Secukinumab 300 mg every 4 weeks group: subjects will receive 2 injections of 
secukinumab 150 mg once weekly for four weeks (at Randomization, Weeks 1, 2, and 3), 
followed by 2 injections of secukinumab 150 mg every four weeks, starting at Week 4 and 
up to Week 12. In order to maintain the treatment blind, subjects will also receive 2 
injections of secukinumab placebo every 4 weeks starting at Week 6, until Week 14.
 


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See Figure 3-1 for graphical representation of type of injection per treatment group and visit.
5.3
Treatment assignment and randomization
The investigator or his/her delegate will contact the IRT after confirming that the subject
fulfills all the inclusion/exclusion criteria. The IRT will assign a randomization number to the 
subject, which will be used to link the subject to a treatment arm and will specify a unique 
medication number for the package of study drug to be dispensed to the subject. The 
randomization number will not be communicated to the caller.
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from subjects and investigator staff. A patient 
randomization list will be produced by the IRT provider using a validated system that 
automates the random assignment of patient numbers to randomization numbers. These 
randomization numbers are linked to the different treatment arms, which in turn are linked to 
medication numbers. A separate medication list will be produced by or under the 
responsibility of Novartis Drug Supply Management using a validated system that automates 
the random assignment of medication numbers to packs containing the investigational drug(s). 
Randomization will not be stratified.
The randomization scheme for subjects will be reviewed and approved by a member of the 
Randomization Group.
5.4
Treatment blinding
Subjects, investigator staff and persons performing the assessments, and data analysts will 
remain blind to the identity of the study treatment from the time of randomization until the 
end of study database lock, using the following methods:
1. Randomization data are kept strictly confidential until the time of unblinding, and will not 
be accessible by anyone else involved in the study with the following exceptions:

Specific vendors whose role in trial conduct requires their unblinding (e.g., IRT)

Drug Supply Management


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
The designated Novartis study team members involved in the primary endpoint
analysis, as described in Section 5.4.1
2. The identity of the treatments will be concealed by the use of investigational treatments 
that are all identical in packaging, labeling, schedule of administration, appearance, taste 
and odor.
Unblinding will only occur in the case of patient emergencies (see Section 5.6), at the time of 
the primary endpoint analysis after all patients have completed Week 16 (see Section 5.4.1) 
and at the conclusion of the study. The appropriate personnel from the study site and Novartis 
will assess whether the study treatment should be discontinued for any subject whose 
treatment code has been broken inadvertently for any reason (see Section 5.5.9). 
 
5.4.1
Unblinding for primary endpoint analysis
If a primary endpoint analysis is performed after all patients have completed Week 16, a small 
selected group of team members (e.g. biostatisticians and programmers involved in the 
analysis, Medical Lead) may have access to the unblinded results. Subjects and site personnel 
directly involved in the conduct of the trial, i.e. investigator staff and persons performing the 
assessments, will remain blinded until the conclusion of the study to ensure study integrity is 
maintained. 
5.5
Treating the patient 
Sponsor qualified medical personnel will be readily available to advise on trial related 
medical questions or problems.
5.5.1
Patient numbering
Each subject is uniquely identified by a Subject Number assigned by Novartis. The Subject 
Number is composed of a site number and a sequential number. Once assigned to a subject, 
the Subject Number will not be reused. 
Upon signing the informed consent form, the subject is assigned the next sequential number 
available in electronic data capture (EDC) system. The investigator or his/her staff will 
contact the IRT and provide the requested identifying information for the subject to register 
them into the IRT. The site must select the case report form (CRF) book with a matching 
Subject Number in the EDC system to enter data. 
If the subject fails to be treated for any reason, the IRT must be notified within 2 days that the 
subject was not treated. The reason for not being treated will be entered on the appropriate 
CRF. 
5.5.2
Dispensing the study drug 
Each study site will be supplied with study drug in packaging of identical appearance.
The study drug packaging has a 2-part label. A unique randomization number is printed on 
each part of this label which corresponds to one of the 2 treatment arms and a specific visit. 


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Investigator staff will identify the study drug package(s) to dispense to the subject by 
contacting the IRT and obtaining the medication number(s). Immediately before dispensing 
the package to the subject, investigator staff will detach the outer part of the label from the 
packaging and affix it to the source document (Drug Label Form) for that subject’s unique 
subject number. 
5.5.3
Handling of study and additional treatment 
5.5.3.1
Handling of study treatment 
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly, and kept in a secured location to which only the investigator and 
designees have access. Upon receipt, all study treatment must be stored according to the 
instructions specified on the labels. Clinical supplies are to be dispensed only in accordance 
with the protocol. Technical complaints are to be reported to the respective Novartis Country 
Pharma Organization Quality Assurance.
Medication labels will be in the local language and comply with the legal requirements of 
each country. They will include storage conditions for the study treatment but no information 
about the subject except for the medication number.
The investigator must maintain an accurate record of the shipment and dispensing of study 
treatment in a drug accountability log. Monitoring of drug accountability will be performed by 
monitors during site visits or remotely and at the completion of the trial. The subjects will 
record the date(s) of administration at home on a diary and will return the used medication 
and packaging at their next visit to the site. Subjects will be asked to return all unused 
medication and packaging the latest at the completion of the study or at the time of 
discontinuation of the investigational treatment. Site staff will record in the appropriate 
documents the dates of the administration. Detailed instructions will be provided separately. 
Patients/subjects will be asked to return all unused study treatment and packaging at the end 
of the study or at the time of discontinuation of study treatment. 
At the conclusion of the study, and as appropriate during the course of the study, the 
investigator will return all unused study treatment, packaging, drug labels, and a copy of the 
completed drug accountability log to the Novartis monitor or to the Novartis address provided 
in the investigator folder at each site.
5.5.3.2
Handling of additional treatment 
Not applicable.


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5.5.4
Instructions for prescribing and taking study treatment
Secukinumab solution for s.c. injection or placebo secukinumab solution (active or placebo, 
respectively) will be provided in pre-filled syringes (PFS).
Each subject will require one box of syringe set (PFS) per dose throughout the study: 

Two secukinumab 150 mg PFS OR

Two secukinumab placebo 150 mg PFS.
All study treatment kits assigned to the subject during the study will be captured in the IRT.
Administration
All doses of study treatment that are administered at the study site should be performed after 
the study assessments for the visit, including blood sampling
 
, have been completed. 
The first study treatment administration will occur at the Randomization/baseline Visit, after 
all study scheduled assessments have been performed (and inclusion/exclusion criteria 
confirmed) and only after the scheduled blood samples have been drawn. Subjects will be 
asked to record details of the doses administered at home on a diary that will be returned to 
the sites at site visits for review and data capture by the site.
Prior to administration the boxes containing the PFSs with study treatment solution should be 
allowed to come to room temperature unopened before administration. Used PFSs should be 
disposed immediately after use in a sharps container OR according to the regulatory needs of 
the respective countries. For details please refer to the pharmacist manual.
The study treatment solution must be injected subcutaneously in non-affected areas of the skin. 
If possible, throughout the trial administer the study treatment to one of the following body 
regions, rotating the injection site from visit to visit: right thigh, left thigh, right stomach, left 
stomach, upper outer arm (when assisted by attendant).
All dates and times of injections during the study must be recorded on the appropriate CRF. 
All kits of study treatment assigned by the IRT will be recorded in the IRT.
Home Administration
Between study visits, subject will be expected to perform home administration in order to 
have administration of study medication every 2 weeks. Home administration can be 
performed by subject or caregiver. 
The following time points are planned for home administrations of study medication:  Weeks 
6, 10, 14, 18, 22, 26, 30, 34, 36, 38, 42, 44, 46 and 48.
At the randomization/baseline visit the subjects will be instructed by the site staff walking 
them through the “Instructions for Use” on how to self-inject via PFS. For subjects willing to 
self-inject, the first administration should be performed under guidance and supervision of a 
site staff member. 


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If the subject or caregiver is not able/confident to perform home administration, the subject 
will be allowed to return to the site for administration of the medication. However, during
those visits no other assessments will be performed. 
During home administration, subjects are expected to contact the investigator/site staff in case 
they are experiencing any AE/SAEs or have any concerns.
The investigator must promote compliance by instructing the subject to take the study 
treatment exactly as prescribed and by stating that compliance is necessary for the subject’s 
safety and the validity of the study. The subject must also be instructed to contact the 
investigator if he/she is unable for any reason to take the study treatment as prescribed.
5.5.5
Permitted dose adjustments and interruptions of study treatment
Investigational or other treatment dose adjustments and/or interruptions are not permitted.
However, for patients who are unable to tolerate the protocol-specified dosing scheme, a dose 
interruption of investigational drug is permitted in order to keep the patient on study drug. A 
maximum of one dose may be missed during each period.
Dosing can be brought forward or delayed by up to 1 week. The subsequent dose should be 
given according to the original schedule (i.e., do not move subsequent dose dates).
These changes must be recorded on the appropriate CRF.
5.5.6
Rescue medication
Rescue medication for psoriasis is not permitted in this study.
5.5.7
Concomitant medication 
The investigator must instruct the subject to notify the study site about any new medications 
taken after enrolling in the study. All medications, procedures and significant non-drug 
therapies (including physical therapy and blood transfusions) administered after the subject
was enrolled into the study must be recorded on the appropriate CRF.
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication. If in doubt the investigator should contact the Novartis medical monitor before 
randomizing a subject or allowing a new medication to be started.
5.5.8
Prohibited medication
Use of any treatments displayed in Table 5-1 that could confound the efficacy are NOT 
allowed during the study for any indication and wash-out periods for these treatments prior to 
randomization are indicated in the table. If the use of these treatments is required, then the 
subject should NOT be randomized into the study.
The investigator should instruct the subject to notify the study site about any new treatments 
he/she takes after the start of the study treatment. All prohibited medications and significant 
non-drug therapies administered after the subject starts treatment with study treatment must be 
listed on CRF.


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If a prohibited treatment listed in Table 5-1 was used during the study, the subject should 
discontinue use of the prohibited treatment if he/she wishes to continue in the study. At the 
discretion of the investigator, if the subject’s use during the study of a prohibited treatment 
listed in Table 5-1 presents undue safety risk for the subject, the subject should be 
discontinued from study treatment as per Section 5.6.2. If the subject received a live virus 
vaccination during the study, the subject must discontinue study treatment.
During the screening period, subjects will be allowed to use some active topical treatments for 
any indication in the following body regions: face, scalp, and genitoanal area. The active 
topical treatments are limited to: mild or moderate potency corticosteroid (CS). The subject 
must stop use of these topical CS at least 12 hours preceding the Randomization visit.
For all other body regions, a washout period of 2 weeks applies for all active topical 
treatments for any indication (Table 5-1).
Table 5-1
Prohibited medication
Prohibited treatments1, 2
Washout 
period 
(before 
randomization)
Note
1If a prohibited treatment of psoriasis is used during the 
study, the subject should discontinue use of the 
prohibited treatment if he/she wishes to continue in the 
study. 
2 In case of undue safety risk for the subject, the subject 
should discontinue study treatment at the discretion of 
the investigator. 
Alefacept, briakinumab, 
efalizumab, ustekinumab
24 weeks
Biological immunomodulating 
agents other than above 
(e.g., adalimumab, etanercept, 
infliximab)
12 weeks 
Other systemic immunomodulating 
treatments
(e.g., Methotrexate, cyclosporine A, 
corticosteroids, cyclophosphamide) 
4 weeks
Other systemic psoriasis 
treatments (e.g. retinoids, 
fumarates, apremilast)
4 weeks
Photochemotherapy (e.g., psoralen 
and ultraviolet A (PUVA)) 
4 weeks
Phototherapy (e.g., UVA, UVB) 
2 weeks 
Topical treatment3,4,5 that is likely to 
impact signs and symptoms of
psoriasis (e.g., corticosteroids [CS], 
vitamin 
D 
analogues, 
pimecrolimus, tacrolimus, retinoids, 
salicylvaseline, salicylic acid, lactic 
acid, tar, urea, -hydroxy or fruit 
acids)
2 weeks 
3 Including intra-articular or peri-articular injections. Note 
that inhaled corticosteroids as well as corticosteroid 
drops in the eye or ear or nasal sprays are permitted. 
4 Mild to moderate topical corticosteroids are allowed 
only during the screening period if used only on the face, 
scalp, hands and feet and/or genitoanal area and if not 
used during the 12 h preceding the randomization visit.
5 Topical corticosteroids and other topical treatments will 
be allowed during treatment period 2 only if (all must 
apply):


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Prohibited treatments1, 2
Washout 
period 
(before 
randomization)
Note
1If a prohibited treatment of psoriasis is used during the 
study, the subject should discontinue use of the 
prohibited treatment if he/she wishes to continue in the 
study. 
2 In case of undue safety risk for the subject, the subject 
should discontinue study treatment at the discretion of 
the investigator. 
•medication was started after the Week 16 visit was 
completed;
•medication was used for 14 consecutive calendar days 
or less;
•medication was used for an indication other than 
psoriasis and not on the area affected with 
psoriasis.
Live vaccinations6
6 weeks
6 If the subject received a live vaccination during the 
study, the subject must discontinue study treatment.
Any investigational treatment or 
participation in any interventional 
trial
4 weeks or 5 
half-lives 
(whichever is 
longer) 
There is no restriction on the use of anti-histamines and on the use of topical corticosteroids in 
the eye, nose or ear.
Exposure to light
Subjects need to be advised to limit exposure to UV light (including sunbathing and/or use of 
UV tanning devices) during the study to avoid possible effect on psoriasis.
5.5.9
Emergency breaking of assigned treatment code
Emergency code breaks must only be undertaken when it is required to in order to treat the 
subject safely. Most often, study treatment discontinuation and knowledge of the possible 
treatment assignments are sufficient to treat a study subject who presents with an emergency 
condition. Emergency treatment code breaks are performed using the IRT. When the 
investigator contacts the system to break a treatment code for a subject, he/she must provide 
the requested subject identifying information and confirm the necessity to break the treatment 
code for the subject. The investigator will then receive details of the investigational drug 
treatment for the specified subject and a fax or email confirming this information. The system 
will automatically inform the Novartis monitor for the site and the Study Team that the code 
has been broken.
It is the investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT/code break cards at any time in case of emergency. The investigator 
will provide:

protocol number

study drug name (if available)

patient number


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In addition, oral and written information to the subject must be provided on how to contact 
his/her backup in cases of emergency, or when he/she is unavailable, to ensure that un-
blinding can be performed at any time. 
5.6
Study completion and discontinuation 
5.6.1
Study completion and post-study treatment 
A subject will be considered to have completed the study when (s)he has completed the last 
visit planned in the protocol.
The investigator must provide follow-up medical care for all subjects who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care.
The information to be collected at this follow-up visit includes concomitant medications, 
adverse events, and survival status.
5.6.2
Discontinuation of study treatment
Discontinuation of study treatment for a subject occurs when study drug is stopped earlier 
than the protocol planned duration.
Subjects may voluntarily discontinue study treatment for any reason at any time. 
The investigator/qualified site staff must discontinue study treatment for a given subject if, on 
balance, he/she believes that continuation would be detrimental to the subject’s well-being.
If discontinuation occurs for any reason in a treatment period, the investigator/qualified site 
staff must make every effort to determine the primary reason for a subject’s discontinuation 
from the study. This information will then be recorded by investigator/qualified site staff on 
the disposition CRF. The investigator must also contact the IRT to register the subject’s 
discontinuation from study treatment. If study drug discontinuation occurs because treatment 
code has been broken (emergency unblinding), please refer to Section 5.5.9.
Study treatment must be discontinued under the following circumstances: 

Subject wish

Withdrawal of consent

Emergence of the following AEs: AEs that in the judgment of the investigator/qualified 
site staff, taking into account the subject’s overall status, prevent the subject from 
continuing study treatment (for example sepsis).

Any laboratory abnormalities that in the judgment of the investigator/qualified site staff, 
and taking into consideration the subject’s overall status, prevents the subject from 
continuing study treatment. 

Pregnancy (see Section 6.5.6 and Section 7.5)

Use of prohibited treatment as per recommendations in Section 5.5.8. 

Any situation in which study participation might result in a safety risk to the subject

Emergency unblinding


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Subjects discontinued from study treatment will NOT be considered discontinued from the 
study. The subject should return to the site after discontinuation of study drug, for an End of 
Treatment (EOT) visit and Follow-up visits (F4 and F8). Assessments detailed in the “End of
Treatment visit” and Follow-up visits (F4 and F8) in Table 6-1 should be completed and 
recorded in the CRF. The investigator must determine the primary reason for the subject’s 
premature discontinuation of study treatment and record this information on the CRF.
At the time of the study treatment discontinuation visit, if it has been approximately 4 weeks
post last dose of study treatment then the assessments described at EOT1 Visit Week 16 (for 
early discontinuation during treatment Period 1) or EOT2 Visit Week 52 (for early 
discontinuation during treatment Period 2) should be completed at this visit.
If it has not been approximately 4 weeks post last dose of study treatment at the time of the 
study treatment discontinuation visit, then the subject should be scheduled to return 4 weeks
post last dose for their EOT1or EOT2 visit as appropriate.
Discontinuation from the post-treatment follow-up period
If premature withdrawal occurs for any reason in the post treatment follow-up period, the 
investigator must make every effort to determine the primary reason for a subject’s premature 
withdrawal from the study and record this information on the appropriate CRF of the 
corresponding period. 
See Section 6 for the required assessments of these subjects who discontinue from the post-
treatment follow-up period.
5.6.3
Withdrawal of informed consent
Subjects may voluntarily withdraw consent to participate in the study for any reason at any 
time. Withdrawal of consent from the study is defined as when a subject:

Does not want to participate in the study anymore
AND

Does not want any further visits or assessments
AND

Does not want any further study related contacts
AND

Does not allow analysis of already obtained biologic material
In this situation, the investigator must make every effort (e.g. telephone, e-mail, letter) to 
determine the primary reason for the subject’s decision to withdraw his/her consent and 
record this information. 
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing. 
Further attempts to contact the subject are not allowed unless safety findings require 
communicating or follow-up.


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All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the subject’s study withdrawal should be made as detailed in the 
assessment Table 6-1.
5.6.4
Loss to follow-up 
For subjects whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or withdraw, the investigator must show "due diligence" by 
documenting in the source documents steps taken to contact the subject, e.g. dates of 
telephone calls, registered letters, etc. A subject cannot be considered as lost to follow-up 
until the time point of his/her scheduled end of study visit has passed.
5.6.5
Early study termination by the sponsor 
The study can be terminated by Novartis at any time for any reason. This may include reasons 
related to the benefit risk assessment of participating in the study, practical reasons, or for 
regulatory or medical reasons (including slow enrollment). Should this be necessary, the 
subject must be seen as soon as possible and treated as a prematurely withdrawn subject. The 
investigator may be informed of additional procedures to be followed in order to ensure that 
adequate consideration is given to the protection of the subject’s interests. The investigator 
will be responsible for informing the Institutional Review Board/Independent Ethics 
Committee (IRBs/IECs) of the early termination of the trial.
6
Visit schedule and assessments
Table 6-1 lists all of the study visits and indicates with an “X” when the assessments are to be 
performed. An ‘S’ indicates the data for that assessment are in the source documents at the 
site. 
Subjects should be seen for all visits on the designated day or as closely as possible to the 
original planned visit schedule. 
If for any reason the subject is a screen failure, the subject may be rescreened. There is no 
restriction on the number of times a potential subject may be rescreened or on how much time 
must pass from the date of screen failure and the date of rescreening. 
If a subject rescreens for the study, then the subject must sign a new ICF and be issued a new 
subject number prior to any screening assessment being conducted for the subject under the 
new screening subject number. For all rescreened subjects, the investigator/qualified site staff 
will record if the subject was rescreened on the rescreening CRF and the original screening 
number the subject was issued prior to the current screening number.
The date of the new informed consent signature must be entered on the Informed consent CRF 
to correspond to the new screening subject number. Informed Consent for a rescreened subject 
must be obtained prior to performing any study-related assessment or collecting any data for 
the Screening Visit. For rescreening, all screening assessments must be performed as per 
protocol, except for the tuberculosis (TB) work up, if applicable, if performed not more than 
12 weeks before randomization.


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If the date of a TB work up is less than 12 weeks from the projected randomization date, then 
it is not required that the TB work up be repeated. However, the subject must repeat the 
Quantiferon test performed by the central laboratory. 
During the treatment periods, subjects may be seen at an unscheduled visit, e.g., if they 
experience deterioration of psoriasis, or AEs that in the opinion of the investigator need 
intervention or repeated laboratory testing. 
Subjects who discontinue study treatment will continue to be followed for safety assessments. 
They are not considered withdrawn from the study.
Subjects who discontinue study treatment before completing the study, and those who 
prematurely withdraw from the study for any reason should be scheduled for a study visit 
4 weeks after their last study treatment administration, at which time all the assessments listed 
for EOT 1 (Week 16)/EOT 2 (Week 52) will be performed. Then, subjects should return to the 
study site for further assessments as indicated under the follow-up visits (F4 and F8). 
If a subject refuses to return for these assessments or are unable to do so, every effort should 
be made to contact them or a knowledgeable informant by telephone or by sending 
appropriate correspondence (i.e. certified letter) immediately. At this contact, the safety (e.g., 
potential occurrence of AE or SAE) and the primary reason for a subject’s premature 
withdrawal should be determined.
At a minimum, subjects who pre-maturely discontinue the treatment will be contacted for 
safety evaluations during the 12 weeks following the last dose of study treatment, including 
final contact at the 12 week point. Documentation of attempts to contact the subject should be 
recorded in the subject record.
Suggested order of assessments:
Suggested guidelines for conduct of the visit assessments are listed below.

Investigator to complete efficacy assessments:
1. IGA
2. PASI
The PASI Score and Investigator’s Global Assessment eCRFs must be completed 
prior to contacting IRT for randomization. At Randomization, the investigator must 
confirm subject meets IGA mod 2011, PASI and BSA eligibility before randomizing 
the subject. 
 

All remaining study procedures (e.g. laboratory sample collection, vital signs
measurements, ECG, etc.) must be completed prior to study treatment dosing

Contact IRT to register the subject visit, as applicable.

Administration of study treatment, as applicable.


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Table 6-1
Assessment schedule
Periods Screen
Treatment Period 1
Treatment Period 2
Unscheduled visit
(a)
Post Treatment 
Follow- up 
Period
Week (relative to 
randomization (R))
≥-4 to
≤-1
R
1
2
3
4
8
12
16
EOT1
20
24
28
32
40
52
EOT2
F4
56
F8 
60
Day
Assessment
≥-28 to
≤-7
1
8
15
22
29
57
85
113
141
169
197
225
281
365
393
421
Site visit
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
Obtain informed consent
X
Demographics
X
Inclusion/exclusion criteria
X
X
Smoking history
X
Psoriasis medical history / 
previous psoriasis therapies
X
Other medical history and prior 
medications
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examination
S
S
S
S
S
S
S
S
S
Height
X
Weight 
X
X
X
X
X
X
Vital signs (blood pressure and
pulse)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
R= Randomization; X = assessment to be recorded on clinical database; S = assessment to be recorded on source documentation.
(a) Unscheduled visit: The assessment(s) performed at an unscheduled visit are at the investigator’s discretion.


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Periods Screen
Treatment Period 1
Treatment Period 2
Unscheduled visit
(a)
Post Treatment 
Follow- up 
Period
Week (relative to 
randomization (R))
≥-4 to
≤-1
R
1
2
3
4
8
12
16
EOT1
20
24
28
32
40
52
EOT2
F4
56
F8 
60
Day
Assessment
≥-28 to
≤-7
1
8
15
22
29
57
85
113
141
169
197
225
281
365
393
421
Laboratory sampling: safety 
panel (Clinical chemistry, 
hematology)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Fasting labs: glucose, lipid 
panel)
X
X
X
X
X
QuantiFERON® TB-Gold In-tube 
test
X
X
X
Serum pregnancy test (WoCBP 
only)
X
Urine pregnancy test (local)
(WoCBP only)
S
S
S
S
S
S
S
S
Urinalysis (local)
X
X
TB: tuberculosis; X = assessment to be recorded on clinical database; S = assessment to be recorded on source documentation; WoCBP = women of child bearing potential 
(a) Unscheduled visit: The assessment(s) performed at an unscheduled visit are at the investigator’s discretion.
 


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Periods Screen
Treatment Period 1
Treatment Period 2
Unscheduled visit
(a)
Post Treatment 
Follow- up 
Period
Week (relative to 
randomization (R))
≥-4 to
≤-1
R
1
2
3
4
8
12
16
EOT1
20
24
28
32
40
52
EOT2
F4
56
F8 
60
Day
Assessment
≥-28 to
≤-7
1
8
15
22
29
57
85
113
141
169
197
225
281
365
393
421
ECG (standard 12-lead)
X
X
X
X
Chest X-ray
(optional)
S
PASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IGA mod 2011
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE/SAE assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Contact IRT
S
S
S
S
S
S
S
S
S
S
S
S
S
S
Administer study treatment 
during visit
X
X
X
X
X
X
X
X
X
X
X
X
X
Review home administration 
diary (c)
S
S
S
S
S
S
S
S
S
S
Study Completion Form
X
ECG: electrocardiogram; eCRF; PASI: Psoriasis Area and Severity Index; IGA: Investigator’s Global Assessment;
; AE: adverse event; IRT: interactive 
response technology; 
X = assessment to be recorded on clinical database; S = assessment to be recorded on source documentation   
(a) Unscheduled visit: The assessment(s) performed at an unscheduled visit are at the investigator’s discretion. 
(c) The following time points are planned for home administrations of study medication:  Weeks 6, 10, 14, 18, 22, 26, 30, 34, 36, 38, 42, 44, 46 and 48.


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6.1
Information to be collected on screening failures 
Subjects who sign the informed consent form and discontinue prior to randomization at 
Visit 2 (Baseline) are considered screening failures.
For each subject who has signed informed consent and discontinued before entering the 
double-blind treatment period, IRT must be notified within 5 days and the reason for not 
being randomized will be entered on the disposition CRF.  In addition, the Screening visit 
date, the Demography CRF, Informed Consent CRF, Inclusion/Exclusion Criteria CRF and   
Subject rescreening CRF must be completed for rescreened subjects. 
Adverse events that are not SAEs will be followed by the investigator and collected only in 
the source data. However, serious adverse events should be recorded in the CRF for any 
serious adverse event (SAEs) that occurred during the screening period. If consent was 
withdrawn during the screening period before the subject was randomized, complete the 
appropriate CRF. 
6.2
Patient demographics/other baseline characteristics 
6.2.1
Demographics
Subject demographic data will include: age, sex, race and ethnicity.
6.2.2
Psoriasis medical history / previous psoriasis therapies
The following information should be collected and entered in the CRF capturing Psoriasis 
history in addition to pre-psoriasis therapies: 

The date of first diagnosis of plaque-type psoriasis (by a physician).

The previous treatments of psoriasis (including previous use of biologic therapies, as 
well as phototherapy and/or photo-chemotherapy) and the reason for discontinuation.
6.2.3
Smoking history
The current and/or previous use of tobacco products will be recorded, as well as the estimated 
number of pack-years based on the approximate consumption per year. 
6.2.4
Co-morbidities – cardiovascular medical history
Any information pertaining to cardiovascular medical history assessed prior to randomization.
6.2.5
Relevant medical history/current medical conditions
Relevant medical history and current medical conditions present before signing the informed 
consent should be recorded in the CRF capturing medical history.
Relevant medical history/current medical condition data includes data up to 6 months prior to 
signing of the informed consent and until the start of study treatment. Whenever possible, 
diagnoses and not symptoms should be recorded.


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Any information pertaining to psoriasis or cardiovascular medical history assessed prior to 
randomization should be reported.
Chest X-ray (optional)
Chest X-ray is an optional assessment which can be performed during screening at the 
discretion of the investigator, if warranted for the subjects. This is aimed to detect ongoing 
infection and particularly tuberculosis or malignancy.
A chest X-ray (or chest MRI at pre specified sites) must only be done after it is fairly certain 
that the subject meets the inclusion/exclusion criteria, in order to minimize unnecessary 
exposure to X-ray radiation for subjects.
If the chest X-ray, CT scan, or MRI evaluated by a qualified physician reveals an evidence of 
untreated infections or malignancies the subject will not be enrolled into the study.
6.2.6
Determination of the tuberculosis status
Determination of the tuberculosis (TB) status will be required before administration of study 
treatment and should be performed as defined by local guidelines. The TB status must be 
determined by medical history, signs, symptoms, TB testing (QuantiFERON-TB Gold assay). 
Any significant findings should be recorded in the TB assessment eCRF and the CRF 
capturing medical history, as deemed necessary. 
QuantiFERON® TB-Gold In-Tube assay
A QuantiFERON® TB-Gold In-Tube assay (QFT) to screen a population for latent 
tuberculosis infection (Doherty et al 2008) will be used at screening to evaluate the subjects’ 
eligibility for the study. This blood-based assay is specific for Mycobacterium tuberculosis 
and is not influenced by previous Bacillus Calmette-Guérin vaccination or by exposure to 
other Mycobacteria species. Furthermore, this test, in contrast to the purified protein 
derivative (PPD) skin test, is also insensitive to a booster effect since the subject is not 
exposed to the vaccine. The assay measures the production of interferon-gamma and presents 
it relative to a negative and a positive control sample (Manuel and Kumar, 2008). The 
QuantiFERON®-TB Gold assay test will be supplied by the central laboratory. Details on the 
collection, shipment of samples and reporting of results by the central laboratory are provided 
to investigators in the study-specific laboratory manual.
The workflow of sample handling in case of positive or indeterminate test results is provided 
in Figure 6-1. 

If the test result is negative, the subject may be randomized.

If the test result is positive, the investigator should perform workup for the test result 
as per local procedures. If a TB workup was conducted prior to the screening the 
subject, results of the workup can be used to assess eligibility if the workup was 
conducted within 12 weeks prior to randomization.
Note: Subjects positive for latent TB per workup may be randomized to the trial if 
sufficient treatment has been initiated according to local routine clinical practice and will 
be maintained for the prescribed duration. Subjects positive for active TB per workup are 
not eligible for the study. Subjects negative for TB (no signs of latent or active TB) per 
workup may be randomized to the trial.


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


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Figure 6-1
Tuberculosis screening flowchart
6.2.7
Other baseline characteristics
Baseline characteristic data to be collected on those indicated with an “X” in Table 6-1
for the screening and randomization visit. 


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6.3
Treatment exposure and compliance
All doses of study treatment administration will be recorded on the appropriate CRF. 
Compliance to the planned administration schedule is expected to be high since most of the 
administrations of study treatment will be done in the presence of the investigator or study
personnel. Compliance will also be assessed by means of site and subject-specific drug 
accountability by Novartis study personnel during the site monitoring visits using 
medication pack numbers, Drug Label Form information and information collected by IRT.
6.4
Efficacy
The following order should be applied when performing the efficacy assessments at study 
visits:

Investigator’s Global Assessment for general psoriasis (IGA mod 2011; scale from 0-4)

Psoriasis Area and Severity Index (PASI; score from 0 – 72)
6.4.1
Investigator Global Assessment (IGA mod 2011)
IGA mod 2011 will be conducted for overall psoriatic disease as indicated in Table 6-2. It is 
recommended that the same evaluator conduct the assessment throughout the study whenever 
possible.
In collaboration with health authorities, in particular the FDA, the IGA mod 2011 scale (see 
Table 6-2) has been developed based on a previous version of the scale used in secukinumab 
Phase 2 studies. The only change from the Phase 2 scale to Phase 3 scale was to condense 
the very severe and severe subjects into one category “severe”. The explanations/descriptions 
of the points on the scale have been improved to ensure appropriate differentiation between 
them.
The IGA mod 2011 used in this study is static, i.e. it refers exclusively to the subject’s disease 
state at the time of the assessments, and does not attempt a comparison with any of the 
subject’s previous disease states, whether at baseline or at a previous visit.
The IGA mod 2011 score will be recorded in the CRF.
Table 6-2
The IGA mod 2011 rating scale
Score
Short Description
Detailed Description
0
Clear
No signs of psoriasis. Post-inflammatory hyperpigmentation may 
be present.
1
Almost clear
Normal to pink coloration of lesions; no thickening; no to minimal 
focal scaling.
2
Mild
Pink to light red coloration; just detectable to mild thickening; 
predominantly fine scaling.
3
Moderate
Dull bright red, clearly distinguishable erythema; clearly 
distinguishable to moderate thickening; moderate scaling.
4
Severe
Bright to deep dark red coloration; severe thickening with hard 
edges; severe / coarse scaling covering almost all or all lesions.
Note: Involvement of nails is not part of the assessment.


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Based on this scale, a subject will be eligible to participate in the study if the subject has an 
IGA mod 2011 score at baseline (Visit 2) of 3 or 4.
Based on this scale, a subject will be considered as IGA mod 2011 0 or 1 responder if the 
subject achieves a score of 0 or 1 and improved by at least 2 points on the IGA scale 
compared to baseline.
6.4.2
Assessment of total Body surface Area and Psoriasis Area Severity 
Index
The investigator or trained qualified designee will complete the PASI assessment as indicated 
in Table 6-1. Whenever possible, the same evaluator should perform this PASI assessment at 
all visits.
The total BSA affected by plaque-type psoriasis will be estimated from the percentages of 
areas affected, including head, trunk, upper limbs and lower limbs (see below for PASI 
assessment). The following calculations will be done: Each reported percentage will be 
multiplied by its respective body region corresponding factor (head = 0.1, trunk = 0.3, upper 
limbs = 0.2, lower limbs = 0.4). The resulting 4 percentages will be added up to estimate the 
total BSA affected by plaque-type psoriasis. The PASI scoring system is further described in 
Table 6-3.
A PASI score (Fredriksson and Pettersson 1978, Weisman et al 2003, Gottlieb et al 2005) will 
be derived as indicated in Table 6-3. The head, trunk, upper limbs and lower limbs are assessed 
separately for erythema, thickening (plaque elevation, induration), and scaling (desquamation).
The average degree of severity of each sign in each of the four body regions is assigned a score 
of 0-4. The area covered by lesions on each body region is estimated as a percentage of the total 
area of that particular body region. Further practical details help the assessment:
1. The neck is assessed as part of the head.
2. The axillae and groin are assessed as part of the trunk.
3. The buttocks are assessed as part of the lower limbs.
When scoring the severity of erythema, scales should not be removed.
Table 6-3
The PASI scoring system
Body region
Erythema (E)
Thickening (plaque 
elevation, 
induration, I)
Scaling 
(desquamation, D)
Area score
(based on true 
area %, A)*
Head (H)†
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=no 
involvement
1=>0-<10%
2=10-<30%
3=30-<50%
4=50-<70%
5=70-<90%
6=90-100%
Trunk (T)‡
0=none 
1=slight 
2=moderate 
3=severe
0=none 
1=slight 
2=moderate 
3=severe
0=none 
1=slight 
2=moderate 
3=severe
0=no 
involvement
1=>0-<10%
2=10-<30%


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4=very severe
4=very severe
4=very severe
3=30-<50%
4=50-<70%
5=70-<90%
6=90-100%
Upper limbs 
(U)
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=no 
involvement
1=>0-<10%
2=10-<30%
3=30-<50%
4=50-<70%
5=70-<90%
6=90-100%
Lower limbs 
(L)§
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=no 
involvement
1=>0-<10%
2=10-<30%
3=30-<50%
4=50-<70%
5=70-<90%
6=90-100%
*
Percentage (not score) of body region (not whole body) affected will be entered in the CRF
†
Neck is assessed as part of the Head (H) body region.
‡
Axillae and groin are assessed as part of the Trunk (T) body region.
§
Buttocks are assessed as part of the Lower limbs (L) body region. 
Because the head and neck, upper limbs, trunk and lower limbs correspond to approximately 
10%, 20%, 30% and 40% of the body surface area, respectively, the PASI score is calculated 
using the formula:
PASI = 0.1 (EH + IH + DH) AH + 0.2 (EU + IU + DU) AU + 0.3 (ET + IT + DT) AT + 0.4 (EL+ IL+
DL) AL
The keys for the letters are provided in Table 6-3.
PASI scores can range from a lower value of 0, corresponding to no signs of psoriasis, up to a 
theoretic maximum of 72.0.
A subject will be considered as a PASI 90 responder if s/he achieves a reduction of 90% or
more of the PASI score, compared to baseline, at a given time point.
During the study, at each visit, the PASI score will be calculated and response will be 
classified according to the definitions from Committee for Medicinal Products for Human Use 
(CHMP) guidelines for psoriasis CHMP/EWP/2454/ 02 2004.


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
PASI 90 response: subjects achieving ≥ 90% improvement (reduction) in PASI score 
compared to baseline 
In addition to the assessment of PASI, the investigator will assess whether new pustular 
psoriasis, or new erythrodermic psoriasis, or more inflammatorypsoriasis occurred (yes/no).
6.4.4
Appropriateness of efficacy assessments 
The PASI score, the assessment of the severity of the psoriasis symptoms and the extent to 
which the subject’s body area is affected by the disease, is considered acceptable by health 
authorities (CHMP/EWP/2454/02 2004) to assess efficacy in conjunction with Investigator’s 
Global Assessment mod 2011 (IGA mod 2011).
6.5
Safety 
All blood draws and safety assessments should be done prior to study treatment 
administration. Appropriate safety assessments (e.g., evaluation of AEs and SAEs including 
injection site reactions) should be repeated after the dose is administered.

Evaluation of all AEs and SAEs including injection site hypersensitivityreactions, vital 
signs, laboratory assessments and occurrence of infections.

Physical examination

Vital signs

Height and weight

Laboratory evaluations (Hematology, Clinical chemistry, Urinalysis)

ECG

Pregnancy and assessments of fertility


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6.5.1
Physical examination
A physical examination, including general appearance, skin, neck, eyes, ears, nose, throat, 
lungs, heart, abdomen, back, lymph nodes, extremities, vascular and neurological systems will 
be performed as indicated in Table 6-1.
If indicated, based on medical history and/or symptoms, additional exams will be performed 
at the discretion of the investigator.
Whenever possible, assessments for an individual subject should be performed by the same 
member of the study site staff throughout the study.
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings that are present prior to the start of the study, i.e. all findings 
prior to signing the informed consent form (ICF), must be included in the CRF capturing
Medical History. Significant findings after enrollment into the study that meets the definition 
of an adverse event must be recorded on the CRF capturing Adverse Event.
6.5.2
Vital signs 
Vital signs (including blood pressure and pulse measurements) will be assessed at every 
scheduled visit as indicated in Table 6-1. Whenever possible, assessments should be
performed by the same study site staff member throughout the study.
After the subject has been sitting for about five minutes, with back supported and both feet
placed on the floor, systolic and diastolic blood pressure will be measured twice and will
be recorded in the source documentation (measurements separated by 1 to 2 minutes)
using a validated device, with an appropriately sized cuff (Mancia et al 2007). In case the
cuff sizes available are not
large enough for the subject’s arm circumference, a
sphygmomanometer with an appropriately sized cuff may be used. The average of the two
measurements will be entered on the CRF capturing Vital Signs. 
Normal blood pressure will be defined as a systolic pressure of 90 to < 120mmHg, and a 
diastolic blood pressure of 60 to < 80 mmHg under measurement conditions as outlined above. 
Notable blood pressure will be hypertension (systolic ≥ 140 mmHg and/or diastolic ≥90 
mmHg) or hypotension (systolic < 90 mmHg and/or diastolic < 60 mmHg). A blood 
pressure indicative of pre-hypertension (systolic 120 to <140 mmHg and/or diastolic 80 to < 
90 mmHg) will not be regarded as notable (Chobanian et al 2003).
A normal pulse rate will be defined as a rate of 60 to 100 beats per minute under the 
measurement conditions outlined above. Notable pulse rates are a rate below 60 bpm 
(bradycardia) or above 100 bpm (tachycardia).
No specific action is pre-defined within this protocol to respond to specific abnormal vital 
signs, as it will be decided by the investigator whether and which specific action needs to be 
taken to respond to any abnormal values, taking into account the overall status of the subject.
6.5.3
Height and weight 
Height and body weight will be measured as listed in Table 6-1.


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Height and body weight will be measured in indoor clothing, but without shoes. Whenever,
possible, body weight assessments should be performed by the same study site staff 
member; the same scale should be used throughout the study.
6.5.4
Laboratory evaluations
A central laboratory will be used for analysis of all specimens listed below, unless noted 
otherwise. Details on the collections, shipment of samples and reporting of results by the 
central laboratory are provided to investigators in the laboratory manual. Refer to the Laboratory 
Manual for identification of laboratory reference range values and the schema for notification of site 
staff and Novartis for out of range values. 
Subjects should avoid smoking within the hour preceding the blood draws. 
Appendix 1 shows the extended laboratory ranges that are considered clinically notable.
No specific action is pre-defined within this protocol to respond to specific abnormal 
laboratory values, as it will be decided by the investigator whether and which specific action 
needs to be taken to respond to any abnormal values, taking into account the overall status of 
the subject.
6.5.4.1
Hematology
Hemoglobin, hematocrit, red blood cell count, white blood cell (WBC) count with differential 
(neutrophils including bands, lymphocytes, monocytes, eosinophils, basophils) and platelet 
count will be measured at all scheduled study visits, within the visit window suggested
in Table 6-1.
6.5.4.2
Clinical chemistry
Serum chemistry will include urea, creatinine, total bilirubin, AST (SGOT), ALT (SGPT), 
Gamma-Glutamyl Transferase (GGT), alkaline phosphatase, sodium, potassium, bicarbonate,
calcium, phosphorous, total protein, albumin, amylase, lipase and uric acid. Serum
chemistry will be measured at all scheduled study visits within the visit window specified
in Table 6-1.
6.5.4.3
Fasting Laboratory evaluations
Fasting (8 hour duration with water ad libitum) laboratory evaluations will be assessed as at 
baseline as indicated in Table 6-1. 
6.5.4.3.1 Plasma glucose
Fasting plasma glucose will be taken as a fasting blood sample as indicated in Table 6-1.
6.5.4.3.2 Lipid panel
A lipid profile including High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), 
cholesterol, triglycerides, lipoprotein (a), apolipoprotein B, apolipoprotein A-1, and 
adiponectin will be measured from a fasting blood sample as indicated in Table 6-1.


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6.5.4.4
Urinalysis
Dipsticks will be provided to the study sites for local urinalysis assessments. The sites
will record the results in the appropriate CRF for each subject. Standard dipstick
measurements for specific gravity, protein, glucose, pH, blood, urine blood dipstick (non-
hemolyzed), urine blood dipstick (hemolyzed), bilirubin, ketones and WBC will be done as
indicated in Table 6-1.
6.5.5
Electrocardiogram (ECG) 
A standard single 12-lead ECG will be ECGs will be measured according to the assessment 
schedule in Table 6-1 and analyzed centrally. 
Each ECG tracing should be labeled with study number, subject number, date and time, and 
filed in the study site source documents. ECGs with subject safety concerns, two additional 
ECGs should be performed to confirm the safety finding. Clinically significant ECG findings 
at screening must be discussed with the sponsor before administration with investigational 
treatment. 
Although there is no exclusion criterion based on ECG results, the ECG at the screening visit 
must be reviewed for major abnormalities prior to dosing. 
Clinically significant abnormalities should be recorded on the relevant section of the CRF 
capturing medical history/ Current medical conditions/AE as appropriate.
6.5.6
Pregnancy and assessments of fertility 
Pregnancy tests will be performed in all women of child-bearing potential (see Section 4.2 for 
definition of child-bearing potential), as indicated in Table 6-1. Additional pregnancy testing 
might be performed if requested by local requirements.
Any woman with a confirmed positive pregnancy test during screening is not eligible for 
randomization. A positive urine pregnancy test during the treatment periods of the study 
requires immediate interruption of study treatment until a serum β-subunit of human 
chorionic gonadotropin (β-hCG) is performed and found to be negative. If the serum β-hCG
test is positive, the subject must be discontinued from the study treatment.
 


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7
Safety monitoring 
7.1
Adverse events 
An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or 
clinical investigation subject after providing written informed consent for participation in the 


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study until the end of study visit. Therefore, an AE may or may not be temporally or causally 
associated with the use of a medicinal (investigational) product.
In addition, all reports of intentional misuse and abuse of the product are also considered an 
adverse event irrespective if a clinical event has occurred.
The occurrence of adverse events must be sought by non-directive questioning of the subject
at each visit during the study. Adverse events also may be detected when they are volunteered 
by the subject during or between visits or through physical examination findings, laboratory 
test findings, or other assessments.
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria:

they induce clinical signs or symptoms, 

they are considered clinically significant, 

they require therapy. 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline or the previous visit, or values which are considered to be non-typical in subject with 
underlying disease. Investigators have the responsibility for managing the safety of individual 
subject and identifying adverse events. Alert ranges for laboratory and other test abnormalities 
are included in Appendix 1.
Adverse events must be recorded in the appropriate CRF capturing Adverse Events under the 
signs, symptoms or diagnosis associated with them, accompanied by the following 
information:

the severity grade

mild: usually transient in nature and generally not interfering with normal activities

moderate: sufficiently discomforting to interfere with normal activities

severe: prevents normal activities

its relationship to the study treatment (suspected: Yes / No)

its duration (start and end dates) or if the event is ongoing an outcome of not 
recovered/not resolved must be reported.

whether it constitutes a serious adverse event (SAE - See Section 7.2 for definition of SAE) 
and which seriousness criteria have been met.

action taken regarding study treatment 
All adverse events must be treated appropriately. Treatment may include one or more of 
the following: 

no action taken (e.g. further observation only) 

study treatment dosage increased/reduced

study treatment interrupted/withdrawn

concomitant medication or non-drug therapy given 

subject hospitalized/subject’s hospitalization prolonged (see Section 7.2 for definition of 
SAE)


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
its outcome (not recovered/not resolved; recovered/resolved; recovered/resolved with 
sequelae; fatal; or unknown)
Once an adverse event is detected, it must be followed until its resolution or until it is judged 
to be permanent, and assessment must be made at each visit (or more frequently, if necessary) 
of any changes in severity, the suspected relationship to the study drug, the interventions 
required to treat it, and the outcome.
Worsening of psoriasis in this study is evaluated via the use of PASI, IGA mod 2011 and 
 is not expected to be captured as an AE in the CRF capturing adverse 
events. Exceptions include cases when a) a new type of psoriasis is diagnosed e.g. guttate 
psoriasis or b) the worsening of psoriasis is so severe that a qualitatively different status is 
reached.
Information about common side effects already known about the investigational drug can be 
found in the Investigator Brochure (IB). This information will be included in the subject
informed consent and should be discussed with the subject during the study as needed. Any 
new information regarding the safety profile of the medicinal product that is identified 
between IB updates will be communicated as appropriate, for example, via an Investigator 
Notification or an Aggregate Safety Finding. New information might require an update to the 
informed consent and has then to be discussed with the subject.
The investigator must also instruct each subject to report any new adverse event (beyond the 
protocol observation period) that the subject, or the subject’s personal physician, believes 
might reasonably be related to study treatment. This information must be recorded in the 
investigator’s source documents; however, if the AE meets the criteria of an SAE, it must be 
reported to Novartis.
7.2
Serious adverse events 
7.2.1
Definition of SAE 
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)]
undesirable sign(s), symptom(s) or medical conditions(s)) which meets any one of the 
following criteria:

is fatal or life-threatening 

results in persistent or significant disability/incapacity

constitutes a congenital anomaly/birth defect

requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:

routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition (specify what this includes)

elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent

treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 


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
social reasons and respite care in the absence of any deterioration in the subject’s 
general condition

is medically significant, e.g. defined as an event that jeopardizes the subject or may 
require medical or surgical intervention.
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met.
Life-threatening in the context of a SAE refers to a reaction in which the subject was at risk of 
death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (please refer to Annex IV, ICH-E2D Guideline).
Medical and scientific judgment should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalization but might jeopardize the 
subject or might require intervention to prevent one of the other outcomes listed above. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization or 
development of dependency or abuse (please refer to Annex IV, ICH-E2D Guideline).
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction.
7.2.2
SAE reporting 
To ensure subject safety, every SAE, regardless of causality, occurring after the subject has 
provided informed consent and until 12 weeks following the last administration of study 
treatment must be reported to Novartis safety within 24 hours of learning of its occurrence. 
Any SAEs experienced after 12 week period following the last administration of study 
treatment should only be reported to Novartis safety if the investigator suspects a causal 
relationship to study treatment. 
All SAEs reported up to the subject’s last visit will be reported in the appropriate eCRF. SAEs 
beyond the last visit will only be recorded in the Novartis Drug Safety and Epidemiology 
database.
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
within 24 hours of the investigator receiving the follow-up information. An SAE occurring at 
a different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event.
Information about all SAEs is collected and recorded on the Serious Adverse Event Report 
Form; all applicable sections of the form must be completed in order to provide a clinically 
thorough report. The investigator must assess the relationship of each SAE to study treatment, 
complete the SAE Report Form in English, and submit the completed form within 24 hours to 
Novartis. Detailed instructions regarding the submission process and requirements for 
signature are to be found in the investigator folder provided to each site. 


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Follow-up information is submitted as instructed in the investigator folder. Each re-
occurrence, complication, or progression of the original event must be reported as a follow-up 
to that event regardless of when it occurs. The follow-up information should describe whether 
the event has resolved or continues, if and how it was treated, whether the blind was broken or 
not, and whether the subject continued or withdrew from study participation.
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert 
(new occurrence) and is thought to be related to the study treatment a Drug Safety and 
Epidemiology Department associate may urgently require further information from the 
investigator for health authority reporting. Novartis may need to issue an Investigator 
Notification (IN) to inform all investigators involved in any study with the same study 
treatment that this SAE has been reported. Suspected Unexpected Serious Adverse Reactions 
(SUSARs) will be collected and reported to the competent authorities and relevant ethics 
committees in accordance with EU Guidance 2011/C 172/01 or as per national regulatory 
requirements in participating countries.
7.3
Liver safety monitoring 
To ensure subject safety and enhance reliability in determining the hepatotoxic potential of an 
investigational drug, a standardized process for identification, monitoring and evaluation of 
liver events has to be followed. 
The following two categories of abnormalities / adverse events have to be considered during 
the course of the study (irrespective of whether classified/reported as (S)AE):

Liver laboratory triggers, which will require repeated assessments of the abnormal 
laboratory parameter

Liver events, which will require close observation, follow-up monitoring should be 
entered into the appropriate CRFs. 
Please refer to Table 13-1 in Appendix 2 for complete definitions of liver laboratory triggers 
and liver events. 
Every liver laboratory trigger or liver event as defined in Table 13-1 in Appendix 2 should be 
followed up by the investigator or designated personal at the trial site as summarized below.
Detailed information is outlined in Table 13-2 in Appendix 2.
For the liver laboratory trigger:

Repeating the liver function test (LFT) within the next week to confirm elevation.
These LFT repeats must be performed using the central laboratory if possible. If this is not 
possible, then the repeats can be performed at a local laboratory to monitor the safety of the 
subject. Repeats laboratory must then be performed at central laboratory as soon as possible. 
If a liver event is subsequently reported, any local LFTs previously conducted that are
associated with this event must be reported on the appropriate CRFs.

If the elevation is confirmed, close observation of the subject will be initiated, including 
consideration of treatment interruption if deemed appropriate.
For the liver events:


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
Repeating the LFT to confirm elevation as appropriate

Discontinuation of the investigational drug if appropriate

Hospitalization of the subject if appropriate

A causality assessment of the liver event via exclusion of alternative causes (e.g., disease, 
co-medications)

An investigation of the liver event which needs to be followed until resolution. 
These investigations can include serology tests, imaging and pathology assessments, 
hepatologist’s consultancy, based on investigator’s discretion. All follow-up information, and 
the procedures performed must be recorded on appropriate CRFs.
7.4
Reporting of study treatment errors including misuse/abuse
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, subject or 
consumer (European Medicines Agency definition).
Misuse refers to situations where the medicinal product is intentionally and inappropriately 
used not in accordance with the protocol.
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects.
Study treatment errors and uses outside of what is foreseen in the protocol will be collected in 
appropriate CRF irrespective of whether or not associated with an AE/SAE and reported to 
Safety only if associated with an SAE. Misuse or abuse will be collected and reported in the 
safety database irrespective of it being associated with an AE/SAE.
Table 7-1 
Guidance for capturing the study treatment errors including 
misuse/abuse
Treatment error 
type
Document in study 
treatment CRF
(Yes/No)
Document in AE 
eCRF
Complete SAE form
Unintentional study 
treatment error
Yes
Only if associated with 
an AE
Only if associated with an 
SAE
Misuse/Abuse
Yes
Yes
Yes, even if not associated 
with a SAE
7.5
Pregnancy reporting 
To ensure subject safety, each pregnancy occurring after signing the informed consent must 
be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should 
be followed up to determine outcome, including spontaneous or voluntary termination, details 
of the birth, and the presence or absence of any birth defects, congenital abnormalities, or 
maternal and/or newborn complications.
Pregnancy must be recorded on the Pharmacovigilance Pregnancy Form and reported by the 
investigator to the local Novartis Drug Safety and Epidemiology Department. Pregnancy 


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follow-up should be recorded on the same form and should include an assessment of the 
possible relationship to the study treatment. 
Any SAE experienced during the pregnancy and unrelated to the pregnancy must be reported 
on a SAE form.
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 data capture requirements (i.e. eCRFs) with the 
investigators and their staff. During the study, Novartis employs several methods of ensuring 
protocol and Good Clinical Practice (GCP) compliance and the quality/integrity of the sites’ 
data. The field monitor will visit the site to check the completeness of patient records, the 
accuracy of data capture / data entry, the adherence to the protocol and to Good Clinical 
Practice, the progress of enrollment, and to ensure that study treatment is being stored, 
dispensed, and accounted for according to specifications. Key study personnel must be 
available to assist the field monitor during these visits. Continuous remote monitoring of each 
site’s data may be performed by a centralized Novartis Clinical Research Associates 
organization. Additionally, a central analytics organization may analyze data and identify 
risks and trends for site operational parameters, and provide reports to Novartis Clinical 
Teams to assist with trial oversight.
The investigator must maintain source documents for each subject in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on CRFs must be traceable to these source documents in the 
subject's file. The investigator must also keep the original informed consent form signed by 
the subject (a signed copy is given to the subject).
The investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the data capture and/or data entry. Novartis monitoring standards 
require full verification for the presence of informed consent, adherence to the 
inclusion/exclusion criteria, documentation of SAEs, and of data that will be used for all 
primary variables. Additional checks of the consistency of the source data with the CRFs are 
performed according to the study-specific monitoring plan. No information in source 
documents about the identity of the subjects will be disclosed.
8.2
Data collection
Designated investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms (eCRFs) using fully validated secure web-enabled software that conforms 
to US CFR 21 Part 11 requirements. Designated investigator site staff will not be given access 
to the system until they have been trained. 
Automatic validation procedures within the system check for data discrepancies during and 
after data entry and, by generating appropriate error messages, allow the data to be confirmed 
or corrected online by the designated investigator site staff. The Investigator must certify that 


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the data entered into the electronic Case Report Forms are complete and accurate. After 
database lock, the investigator will receive copies of the subject data for archiving at the 
investigational site. 
8.3
Database management and quality control 
Novartis personnel (or designated Contract Research Organization (CRO) will review the data 
entered by investigational staff for completeness and accuracy. Electronic data queries stating 
the nature of the problem and requesting clarification will be created for discrepancies and 
missing values and sent to the investigational site via the EDC system. Designated 
investigator site staff is required to respond promptly to queries and to make any necessary 
changes to the data. 
Concomitant medications entered into the database will be coded using the World Health 
Organization (WHO) Drug Reference List, which employs the Anatomical Therapeutic 
Chemical classification system. Concomitant procedures, non-drug therapies and adverse 
events will be coded using the Medical dictionary for regulatory activities (MedDRA) 
terminology.
Laboratory samples will be processed centrally and the results will be sent electronically to 
Novartis (or a designated CRO).
ECGs will be analyzed centrally and results will be sent electronically to Novartis (or a 
designated CRO). Any clinically significant findings will be reported as (cardiovascular) 
medical history or AE depending upon timing of ECG assessment compared to screening.
 
 
Randomization codes and data about all study drug(s) dispensed to the subject and all dosage 
changes will be tracked using an Interactive Response Technology (IRT). The system will be 
supplied by a vendor, who will also manage the database. The data will be sent electronically 
to Novartis (or a designated CRO).
Each occurrence of a code break via IRT will be reported to the clinical team and monitor. 
The code break functionality will remain available until study shut down or upon request of 
Novartis. 
The occurrence of relevant protocol deviations will be determined. After these actions have 
been completed and the database has been declared to be complete and accurate, it will be 
locked and the treatment codes will be unblinded and made available for data analysis. Any 
changes to the database after that time can only be made after written agreement by Novartis 
Development management.
8.4
Data Monitoring Committee 
Not required.


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8.5
Adjudication Committee 
Not required.
9
Data analysis 
The analysis will be conducted on all subject data at the time the trial ends. Any data analysis 
carried out independently by the investigator should be submitted to Novartis before 
publication or presentation.
9.1
Analysis sets 
The following analysis sets will be used in this trial:
Randomized set: The randomized set will be defined as all subjects who were randomized. 
Unless otherwise specified, mis-randomized subjects (mis-randomized in IRT) will be 
excluded from the randomized set. 
Full analysis set (FAS): The FAS will be comprised of all subjects from the randomized set 
to whom study treatment has been assigned. Following the intent-to-treat principle, subjects 
will be analyzed according to the treatment assigned to at randomization. 
Safety set (SAF): The safety set includes all subjects who took at least one dose of study
treatment during the treatment period. Subjects will be analyzed according to treatment 
received.
9.2
Patient demographics and other baseline characteristics 
Demographics and baseline characteristics
Summary statistics will be presented for continuous demographic and baseline characteristic 
variables for each treatment group and for all subjects in the randomized set. The number and 
percentage of subjects in each category will be presented for categorical variables for each 
treatment group and for all subjects.
Medical history
Any condition entered as medical history or current medical conditions at baseline will be 
coded using the MedDRA dictionary. Medical history will be summarized by system organ 
class and preferred term in the MedDRA dictionary. Summaries for psoriasis specific medical 
history will be provided as well.
9.3
Treatments 
Study treatments
The analysis of study treatment data will be based on the safety set.
The number of active and placebo injections will be summarized by treatment group by means 
of contingency tables.


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The duration of exposure to study treatment will also be summarized by treatment group. In 
addition, the number of subjects with exposure of at least certain thresholds (e.g., any 
exposure, ≥1 week, ≥2 weeks, ≥3 weeks, ≥4 weeks, ≥8 weeks, etc.) will be displayed.
Prior and concomitant treatments
Prior and concomitant treatments will be summarized by treatment group in separate tables 
for the safety set.
Prior treatments are defined as treatments taken and stopped prior to first dose of study 
treatment. Any treatment given at least once between the day of first dose of randomized
study treatment and the last day of study visit will be a concomitant treatment, including those 
which were started pre-baseline and continued into the treatment period.
Treatments will be presented in alphabetical order, by Anatomical Therapeutic Chemical 
(ATC) codes and main groups. Tables will also show the overall number and percentage of 
subjects receiving at least one treatment of a particular ATC code and at least one treatment in 
a particular anatomical main group.
Psoriasis specific prior treatments will be presented as well including number of prior 
systemic and biologic psoriasis therapies as well as reason for discontinuation.
In addition, medical procedures and significant non-drug therapies as coded in MedDRA will 
be summarized.
9.4
Analysis of the primary variable(s)
This section will detail the statistical analysis of the primary endpoint. Details of the 
hypothesis testing strategy including primary and secondary endpoints to handle multiplicity 
are provided in Section 9.5.1.
9.4.1
Primary Variable(s)
The primary efficacy variable is PASI 90 response at Week 16. The analysis of primary 
variable will be based on the FAS.
9.4.2
Statistical model, hypothesis, and method of analysis
The statistical hypothesis for PASI 90 response at Week 16 being tested is that secukinumab 
300 mg every 2 weeks is not superior in the proportion of subjects with PASI 90 response at 
Week 16 versus secukinumab 300 mg every 4 weeks.
 
The following hypotheses will be tested
H1: p1 – p0 ≤0 versus HA1: p1 – p0 > 0,
In other words:


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H1: secukinumab 300 mg every 2 weeks is not superior to secukinumab 300 mg every 
4 weeks with respect to PASI 90 response at Week 16.
The primary analysis method will be the logistic regression model with treatment group and
baseline weight, baseline PASI score as explanatory variables. Odds ratio will be computed 
for the comparison of secukinumab 300 mg every 2 weeks versus secukinumab 300 mg every 
4 weeks utilizing the logistical regression model fitted. In case of non-convergence, Fisher’s 
exact test will be applied. Confidence intervals for risk difference will be provided.
The hypotheses H1 will be tested at level 2.5% (one-sided).
9.4.3
Handling of missing values/censoring/discontinuations
Response variables based on PASI score and IGA mod 2011 score will be imputed with 
multiple imputation (MI) as primary imputation method for the missing values. Multiple 
imputation (MI) is a simulation based approach where missing values are replaced by multiple 
Bayesian draws from the conditional distribution of missing data given the observed data and 
covariates, creating multiple completed data sets. These completed data sets can then be 
analyzed using standard methods. Within this analysis the PASI score or IGA mod 2011 
categories will be imputed and response variables will be derived based on the imputed scores. 
In the multiple imputation analysis the response status will be imputed based on the individual 
treatment arm information.
9.4.4
Sensitivity analyses 
Primary variable and key secondary variable will be evaluated using logistic regression as 
described in primary analysis method with modified non-responder imputation.
Missing values with respect to response variables based on PASI score and IGA mod 2011 
score will be imputed with non-response regardless of the reason for missing data (e.g., 
premature study discontinuation, missed visit, administrative issues), with the exception of the 
followings:

If a subject dropped out the study prior to last scheduled visit and being responder 
consecutively at least for two preceding visits, the subject will be imputed as responder for 
the last scheduled visit.

If a subject who was responder at visit x-1 and visit x+1 but has missing data at visit x, 
then the subject will be imputed as responder for visit x, except for the missing data at last 
visit in the treatment period.
9.5
Analysis of secondary variables
9.5.1
Efficacy variables 
The secondary variable in testing strategy is the IGA mod 2011 0 or 1 response at Week 16
(for superiority comparison of secukinumab 300 mg every 2 weeks versus secukinumab
300 mg every 4 weeks). The IGA mod 2011 0 or 1 response at Week 16 will be analyzed 
analogously to PASI 90 response at Week 16 (i.e., logistic regression analysis).
The analysis of secondary variable will be based on FAS.


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H2:
secukinumab 300 mg every 2 weeks is not superior to secukinumab 300 mg every 
4 weeks with respect to IGA mod 2011 0 or 1 response at Week 16.
Testing strategy
The family-wise type-I-error will be set to α=2.5% (one-sided). The graphical approach of 
Bretz (Bretz et al 2009) for sequentially rejective testing procedures is used to illustrate the 
hierarchical testing strategy.
One-sided p-values will be derived. Each hypothesis is tested sequentially at α=2.5% (one-
sided). The testing sequence will continue to H2 at α (one-sided) only if H1 has been rejected.
9.5.2
Safety variables
All safety evaluations will be performed on the Safety set.
Adverse events
Treatment-emergent adverse events will be summarized. Only primary paths within MedDRA 
will be considered for adverse event reporting. The definition for “treatment-emergent” is as 
follows:

Events started after the first dose of study medication or events present prior to the first 
dose of study medication but increased in severity based on preferred term

Started prior to the last dose plus 84 days (inclusive)
AEs will be summarized by presenting, for each treatment group, the number and percentage 
of subjects having at least one AE, having an AE in each primary system organ class and 
having each individual AE (preferred term). 
Summaries will also be presented for AEs by severity and for study treatment related AEs. If 
a particular AE ‘severity’ is missing, this variable will be listed as missing and treated as 
missing in summaries. If a subject reported more than one adverse event with the same 
preferred term, the adverse event with the greatest severity will be presented. If a subject 
reported more than one adverse event within the same primary system organ class, the subject 
will be counted only once with the greatest severity at the system organ class level, where 
applicable.


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Confidence intervals for relative frequencies will be derived as well according to the score 
method including continuity correction by Newcombe (Newcombe 1998).
Separate summaries will be provided for death, serious adverse event, other significant 
adverse events leading to discontinuation and adverse events leading to dose adjustment 
(including study treatment discontinuation).
Exposure adjusted incidence rates will be provided for selected adverse events. 
Laboratory data
The summary of laboratory evaluation will be presented for three groups of laboratory tests 
(hematology, serum chemistry and urinalysis). Descriptive summary statistics for the change 
from baseline to each study visit will be presented by laboratory test group, laboratory tests 
(i.e., lab parameters) and treatment group. Change from baseline will only be summarized for 
subjects with both baseline and post baseline.
For each lab parameter, the maximum change (maximum decrease and maximum increase) 
from baseline will be analyzed analogously.
In addition, shift tables will be provided for all lab parameters to compare a subject’s baseline 
laboratory evaluation relative to the most extreme post-baseline laboratory test value. For the 
shift tables, the normal laboratory ranges will be used to evaluate whether a particular 
laboratory test value was normal, low, or high for each visit value relative to whether or not 
the baseline value was normal, low or high. These summaries will be presented by laboratory 
test and treatment group.
Vital signs
Analysis in vital sign measurement using descriptive summary statistics for the change from 
baseline for each post-baseline visit will be performed by vital sign and treatment group. 
Change from baseline will only be summarized for subjects with both baseline and post-
baseline values.
ECG
Summary statistics will be presented for ECG variables by visit and treatment group.


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9.7
Interim Analyses
A primary endpoint analysis (PEA) may be conducted when all subjects have completed the 
Week 16 visit at which the primary endpoint is assessed. Additional analyses may be 
performed to support health authority interactions as necessary.


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9.8
Sample size calculation
The sample size has been calculated to detect a clinical relevant treatment difference (i.e. 15%) 
between secukinumab 300 mg every two weeks and secukinumab 300 mg every four weeks. 
Based on this, the total sample size is approximately 330 subjects, with body weight ≥ 90 kg 
at randomization. i.e., 165 subjects will be randomized to each dose regimen (300 g every 2 
weeks and 300 mg every 4 weeks) using a balanced randomization.
Secukinumab 300 mg every two weeks will be tested versus secukinumab 300 mg every four 
weeks with respect to the primary endpoint PASI 90 response at Week 16, and sequentially 
the secondary endpoint IGA mod 2011 0 or 1 at Week 16. The family-wise type-I-error will 
be 2.5% (one-sided)
 
 
 
 
 
 
10
Ethical considerations 
10.1
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in 
accordance with the International Conference on Harmonisation (ICH) Harmonized Tripartite 
Guidelines for Good Clinical Practice, with applicable local regulations (including European 
Directive 2001/20/EC, US CFR 21, and Japanese Ministry of Health, Labor, and Welfare), 
and with the ethical principles laid down in the Declaration of Helsinki.
10.2
Informed consent procedures 
Eligible subjects may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent, or, if applicable after 
such consent has been provided by a legally acceptable representative(s) of the subject. In 
cases where the subject’s representative gives consent, the subject must be informed about the 
study to the extent possible given his/her understanding. If the subject is capable of doing so, 
he/she must indicate assent by personally signing and dating the written informed consent 
document or a separate assent form. Informed consent must be obtained before conducting 
any study-specific procedures (e.g. all of the procedures described in the protocol). The 
process of obtaining informed consent must be documented in the subject source documents. 
Novartis will provide to investigators in a separate document a proposed informed consent 
form that complies with the ICH GCP guideline and regulatory requirements and is 


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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 must be informed that taking the study treatment may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that 
in order to participate in the study they must adhere to the contraception requirement for the 
duration of the study. If there is any question that the subject will not reliably comply, they 
must not be entered in the study.
10.3
Responsibilities of the investigator and IRB/IEC
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion 
from the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial 
protocol, written informed consent form, consent form updates, subject recruitment 
procedures (e.g., advertisements) and any other written information to be provided to subjects. 
Prior to study start, the investigator is required to sign a protocol signature page confirming 
his/her agreement to conduct the study in accordance with these documents and all of the 
instructions and procedures found in this protocol and to give access to all relevant data and 
records to Novartis monitors, auditors, Novartis Quality Assurance representatives, designated 
agents of Novartis, IRBs/IECs, and regulatory authorities as required. If an inspection of the 
clinical site is requested by a regulatory authority, the investigator must inform Novartis 
immediately that this request has been made.
10.4
Publication of study protocol and results
The key design elements of this protocol will be posted in a publicly accessible database such 
as clinicaltrials.gov. In addition, upon study completion and finalization of the study report 
the results of this trial will be either submitted for publication and/or posted in a publicly 
accessible database of clinical trial results.
10.5
Quality Control and Quality Assurance 
Novartis maintains a robust Quality Management (QM) system that includes all activities 
involved in quality assurance and quality control, including the assignment of roles and 
responsibilities, the reporting of results, and the documentation of actions and escalation of 
issues identified during the review of quality metrics, incidents, audits and inspections.
Audits of investigator sites, vendors, and Novartis systems are performed by Novartis Pharma 
Auditing and Compliance Quality Assurance, a group independent from those involved in 
conducting, monitoring or performing quality control of the clinical trial. The clinical audit 
process uses a knowledge/risk based approach.
Audits are conducted to assess GCP compliance with global and local regulatory requirements, 
protocols and internal Standard Operating Procedures (SOPs), and are performed according to 
written Novartis processes.


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11
Protocol adherence 
This protocol defines the study objectives, the study procedures and the data to be collected 
on study participants. Additional assessments required to ensure safety of subjects should be 
administered as deemed necessary on a case by case basis. Under no circumstances is an 
investigator allowed to collect additional data or conduct any additional procedures for any 
research related purpose involving any investigational drugs under the protocol.
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and health authorities, where required, it cannot be 
implemented. 
11.1
Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation. Only amendments that are intended to eliminate an apparent immediate 
hazard to subjects may be implemented immediately provided the health authorities are 
subsequently notified by protocol amendment and the reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any subject included in this 
study, even if this action represents a deviation from the protocol. In such cases, the reporting 
requirements identified in Section 7 Safety Monitoring must be followed.
12
References 
References are available upon request.
Bretz F, Maurer W, Brannath W, et al (2009) A graphical approach to sequentially rejective 
multiple test procedures. Statist. Med; 28:586-604.
Chobanian AV, Bakris GL, Black HR, et al (2003) Seventh Report of the Joint National 
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. 
Hypertension; 42:1206-1252.
Committee for medicinal products for human use (CHMP), European Medicines Agency for 
the Evaluation of Medicines for Human Use (2004) Guideline on clinical investigation of 
medicinal products indicated for the treatment of psoriasis. CHMP/EWP/2454/02 corr 
document. London, UK.
Doherty SD, Van Voorhees A, Lebwohl MG, et al (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. 
 
 


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Fredriksson T, Pettersson U (1978) Severe Psoriasis – Oral Therapy with a New Retinoid.  
Dermatologica; 157:238-244.
Gottlieb AB, Griffiths CEM, Ho VC, et al (2005) Oral pimecrolimus in the treatment of 
moderate to severe chronic plaque-type psoriasis: a double –blind, multicenter, randomized, 
dose-finding trial. British Journal of Dermatology; 152:1219-1227.
Kimball AB, Wu EQ, Guerin A, et al (2012) Risk of developing psychiatric disorders in 
pediatric patients with psoriasis. J Am Acad Dermatol; 67 (4):651-7.
Langley RG, Elewski BE, Lebwohl M, et al (2014) Secukinumab in Plaque Psoriasis-Results 
of Two Phase 3 Trials. N ENGL J MED; 371 (4): 326-338.
Mancia G, De Backer G, Dominiczak A, et al (2007) 2007 Guidelines for the Management of 
Arterial Hypertension. Journal of Hypertension; 25:1105-1187.
Manuel O, Kumar D (2008) QuantiFERON-TB Gold assay for the diagnosis of latent 
tuberculosis infection. Expert rev. Mol. Diagn; 8(3):247-255.
Newcombe RG (1998) Two-sided confidence intervals for the single proportion: comparison 
of seven methods. Statistics in Medicine; 17:857-872.
Papp KA (2006) The long-term efficacy and safety of new biological therapies for psoriasis. 
Arch Dermatol Res; 298:7-15.
Papp KA, Langley RG, Lebwohl M, et al (2008) Efficacy and Safety of ustekinumab, a 
human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results 
from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet; 371:1675-
84.
Thaci D, Blauvelt A, Reich K, et al (2015) Secukinumab is superior to ustekinumab in 
clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized 
controlled trial. J Am ACAD Dermatol; 73 (3):400-409.
van Lümig PPM, Lecluse LLA, Driessen RJB, et al (2010) Switching from etanercept to 
adalimumab is effective and safe: results in 30 patients with psoriasis with primary failure, 
secondary failure or intolerance to etanercept. British Journal of Dermatology; 163:838-846.
Weisman S, Pollack CR, Gottschalk RW (2003) Psoriasis disease severity measures: 
comparing efficacy of treatments for severe psoriasis. Journal of Dermatological Treatment; 
14:158-165. 


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13
Appendices
13.1
Appendix 1: Clinically notable laboratory values and vital signs
The following criteria will be used to define expanded limits and notable abnormalities of key 
laboratory tests. Notable values for blood pressure and pulse are presented in Section 6.5.2.
No specific action is pre-defined within this protocol to respond to specific abnormal 
laboratory values, as it will be decided by the investigator whether and which specific action 
needs to be taken to respond to any abnormal values, taking into account the overall status of 
the subject.
Liver Function and Related Variables

Alanine transaminase (ALT) (SGPT):
> 3 x Upper Limit of Normal (ULN)

Aspartate transaminase (AST) (SGOT): > 3 x ULN

Total bilirubin:
> 2 x ULN

Alkaline phosphatase:
> 2.5 x ULN
Hematology Variables

Hemoglobin:
≥ 20 g/dL decrease from baseline

Platelet count:
< Lower Limit of Normal (LLN)

White blood cell count:
< 0.8 x LLN

Neutrophils:
< 0.9 x LLN

Eosinophils:
> 1.1 x ULN

Lymphocytes:
> 1.1 x ULN


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13.2
Appendix 2: Liver event and Laboratory trigger Definitions and 
Follow-up Requirements
Table 13-1
Liver Event and Laboratory Trigger Definitions
Definition/ threshold
LIVER LABORATORY TRIGGERS

3 x ULN < ALT / AST 5 x ULN

1.5 x ULN < TBL 2 x ULN
LIVER EVENTS

ALT or AST > 5 × ULN

ALP > 2 × ULN (in the absence of known bone pathology)

TBL > 2 × ULN (in the absence of known Gilbert syndrome)

ALT or AST > 3 × ULN and INR > 1.5 

Potential Hy’s Law cases (defined as ALT or AST > 3 × ULN and 
TBL > 2 × ULN [mainly conjugated fraction] without notable 
increase in ALP to > 2 × ULN)

Any clinical event of jaundice (or equivalent term)

ALT or AST > 3 × ULN accompanied by (general) malaise, fatigue, 
abdominal pain, nausea, or vomiting, or rash with eosinophilia

Any adverse event potentially indicative of a liver toxicity*
*These events cover the following: hepatic failure, fibrosis and cirrhosis, and other liver damage-related 
conditions; the non-infectious hepatitis; the benign, malignant and unspecified liver neoplasms
TBL: total bilirubin; ULN: upper limit of normal; INR: international normalized ratio
Table 13-2
Follow-up Requirements for Liver Events and Laboratory Triggers
Criteria
Actions required
Follow-up monitoring
Potential Hy’s Law 
casea

Discontinue the study treatment 
immediately

Hospitalize, if clinically appropriate

Establish causality

Complete appropriate CRF to record the 
AE and any contributory factors
ALT, AST, TBL, Alb, PT/INR, ALP and 
GGT until resolutionc (frequency at 
investigator discretion)
ALT or AST
> 8 × ULN

Discontinue the study treatment 
immediately

Hospitalize if clinically appropriate

Establish causality

Complete appropriate CRF to record the 
AE and any contributory factors
ALT, AST, TBL, Alb, PT/INR, ALP and 
GGT until resolutionc (frequency at 
investigator discretion)
> 3 × ULN and INR > 
1.5

Discontinue the study treatment 
immediately

Hospitalize, if clinically appropriate

Establish causality

Complete appropriate CRF to record the 
AE and any contributory factors
ALT, AST, TBL, Alb, PT/INR, ALP and 
GGT until resolutionc (frequency at 
investigator discretion)
> 5 to ≤ 8 × ULN

Repeat LFT within 48 hours

If elevation persists, continue follow-up 
monitoring

If elevation persists for more than 2 
weeks, discontinue the study drug
ALT, AST, TBL, Alb, PT/INR, ALP and 
GGT until resolutionc (frequency at 
investigator discretion)


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Criteria
Actions required
Follow-up monitoring

Establish causality

Complete appropriate CRF to record the 
AE and any contributory factors
> 3 × ULN 
accompanied by 
symptomsb

Discontinue the study treatment 
immediately

Hospitalize if clinically appropriate

Establish causality

Complete appropriate CRF to record the 
AE and any contributory factors
ALT, AST, TBL, Alb, PT/INR, ALP and 
GGT until resolutionc (frequency at 
investigator discretion)
> 3 to ≤ 5 × ULN 
(patient is 
asymptomatic)

Repeat LFT within the next week

If elevation is confirmed, initiate close 
observation of the patient
Investigator discretion
Monitor LFT within 1 to 4 weeks
ALP (isolated)
> 2 × ULN (in the 
absence of known 
bone pathology)

Repeat LFT within 48 hours

If elevation persists, establish causality

Complete appropriate CRF to record the 
AE and any contributory factors
Investigator discretion
Monitor LFT within 1 to 4 weeks or at 
next visit
TBL (isolated)
> 2 × ULN (in the 
absence of known 
Gilbert syndrome)

Repeat LFT within 48 hours

If elevation persists, discontinue the study 
drug immediately

Hospitalize if clinically appropriate

Establish causality

Complete appropriate CRF to record the 
AE and any contributory factors
ALT, AST, TBL, Alb, PT/INR, ALP and 
GGT until resolutionc (frequency at 
investigator discretion)
Test for hemolysis (e.g., reticulocytes, 
haptoglobin, unconjugated [indirect] 
bilirubin)
> 1.5 to ≤ 2 × ULN
(patient is 
asymptomatic)

Repeat LFT within the next week

If elevation is confirmed, initiate close 
observation of the patient 
Investigator discretion
Monitor LFT within 1 to 4 weeks or at 
next visit
Jaundice

Discontinue the study treatment 
immediately

Hospitalize the patient

Establish causality

Complete appropriate CRF to record the 
AE and any contributory factors
ALT, AST, TBL, Alb, PT/INR, ALP and 
GGT until resolutionc (frequency at 
investigator discretion)
Any AE potentially 
indicative of a liver 
toxicity*

Consider study treatment interruption or 
discontinuation 

Hospitalization if clinically appropriate

Establish causality

Complete appropriate CRF to record the 
AE and any contributory factors
Investigator discretion
aElevated ALT/AST > 3 × ULN and TBL > 2 × ULN but without notable increase in ALP to > 2 × ULN
b(General) malaise, fatigue, abdominal pain, nausea, or vomiting, or rash with eosinophilia 
cResolution is defined as an outcome of one of the following: (1) return to baseline values, (2) stable values at 
three subsequent monitoring visits at least 2 weeks apart, (3) remain at elevated level after a maximum of 
6 months, (4) liver transplantation, and (5) death.


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SAP_001.pdf: 


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Document History – Changes compared to previous final version of SAP 
 
Date 
Time 
point 
Reason for update 
Outcome for 
update 
Section and 
title impacted 
(Current) 
31-May-
2018 
Prior 
FPFV 
Creation of final version 
First version 
NA 
27-Sep-
2019 
Before 
Week 16 
DBL 
Add details for Week 16 
analysis. 
Drop 
exposure 
adjusted 
incidence rate for adverse 
event summary. 
Amendment 
v1.0 
Section 2.14 
22-Aug-
2020 
Before 
Week 52 
DBL 
Added details of protocol 
deviation listing for protocol 
deviations due to COVID 19  
Amendment 
v2.0 
Section 2.3.1 
 
 
Visit Windows for FU period 
Week 56 and 60 added and 
added more details for safety 
assessments end at week 52. 
 
Section 2.4.2 
 
 
Added subsection numbers 
and clarity on section 2.3 
 
Section 2.3 
 
 
Removed exposure adjusted 
analysis related text  
 
Section 2.8.1, 
2.8.2, 2.8.4 
 
 
Listing 
of 
SAE 
occured 
during screening removed  
 
Section 2.8.1 
 
 
Removed dot plots  
 
Section 5.4.2.1 
 
 
Other minor edits  
 
 
 


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Table of contents 
Table of contents ............................................................................................................. 3 
List of abbreviations ........................................................................................................ 5 
1 
Introduction .................................................................................................................... 6 
1.1 
Study design ........................................................................................................ 6 
1.2 
Study objectives and endpoints ............................................................................ 8 
2 
Statistical methods .......................................................................................................... 9 
2.1 
Data analysis general information ........................................................................ 9 
2.1.1 
General definitions ............................................................................. 10 
2.1.2 
Study treatment .................................................................................. 10 
2.1.3 
Study Day 1 and other study days ...................................................... 10 
2.1.4 
Screening, baseline and post-baseline definitions ............................... 10 
2.1.5 
Day of last dose of randomized study treatment ................................. 11 
2.2 
Analysis sets ...................................................................................................... 11 
2.2.1 
Subgroup of interest ........................................................................... 11 
2.3 
Patient disposition, demographics and other baseline characteristics .................. 11 
2.3.1 
Patient disposition .............................................................................. 11 
2.3.2 
Demographics and baseline characteristics ......................................... 12 
2.4 
Treatments (study treatment, rescue medication, concomitant therapies, 
compliance) ....................................................................................................... 13 
2.4.1 
Study treatment / compliance ............................................................. 13 
2.4.2 
Visit window ..................................................................................... 14 
2.4.3 
Multiple assessments within visit windows ........................................ 15 
2.4.4 
Prior, concomitant and post therapies ................................................. 16 
2.5 
Analysis of the primary objective ....................................................................... 17 
2.5.1 
Primary endpoint ............................................................................... 18 
2.5.2 
Definition of PASI and related variables ............................................ 18 
2.5.3 
Definition of IGA mod 2011 score and IGA mod 2011 0 or 1 
response ............................................................................................. 20 
2.5.4 
Statistical hypothesis, model, and method of analysis ......................... 20 
2.5.5 
Handling of missing values/censoring/discontinuations ...................... 21 
2.5.6 
Supportive analyses ........................................................................... 21 
2.6 
Analysis of the key secondary objective ............................................................. 22 
2.6.1 
Secondary endpoint ............................................................................ 22 
2.6.2 
Statistical hypothesis, model, and method of analysis ......................... 22 
2.6.3 
Handling of missing values/censoring/discontinuations ...................... 22 
2.7 
Analysis of secondary efficacy objective(s)........................................................ 22 


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2.7.1 
Secondary endpoints .......................................................................... 23 
2.7.2 
Statistical hypothesis, model, and method of analysis ......................... 23 
2.7.3 
Handling of missing values/censoring/discontinuations ...................... 23 
2.8 
Safety analyses .................................................................................................. 23 
2.8.1 
Adverse events (AEs) ........................................................................ 23 
2.8.2 
Adverse events of special interest / grouping of AEs .......................... 24 
2.8.3 
Deaths................................................................................................ 25 
2.8.4 
Laboratory data .................................................................................. 25 
2.8.5 
Other safety data ................................................................................ 27 
 
 28 
 
 29 
 
 29 
 
 29 
 
 29 
 
 29 
2.14 
Interim analysis ................................................................................................. 30 
3 
Sample size calculation ................................................................................................. 31 
4 
Change to protocol specified analyses ........................................................................... 31 
5 
Appendix ...................................................................................................................... 31 
5.1 
Imputation rules ................................................................................................. 31 
5.1.1 
Study drug ......................................................................................... 31 
5.1.2 
AE date imputation ............................................................................ 31 
5.1.3 
Concomitant medication date imputation ........................................... 32 
5.2 
AEs coding/grading ........................................................................................... 34 
5.3 
Laboratory parameters derivations ..................................................................... 34 
5.4 
Statistical models ............................................................................................... 34 
5.4.1 
Primary analysis ................................................................................ 34 
5.4.2 
Secondary analysis ............................................................................. 38 
5.5 
Rule of exclusion criteria of analysis sets ........................................................... 39 
6 
Reference ...................................................................................................................... 40 


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List of abbreviations 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alkanine aminotransferase/glutamic pyruvic transaminase/GPT 
AST 
Aspartate aminotransferase/glutamic oxaloacetic transaminase/GOT 
ATC 
Anatomical Therapeutic Classification 
BMI 
Body Mass Index 
BSA 
Body surface area 
CHMP  
Committee for medicinal products for human use  
CSR 
Clinical study report 
CTC 
Common Toxicity Criteria 
CTCAE 
Common Terminology Criteria for Adverse Events 
COVID-19 
Corona Virus Disease 2019 
 
 
eCRF 
Electronic Case Report Form 
FAS 
Full Analysis Set 
FDA 
United States Food and Drug Administration 
GGT 
Gamma-glutamyl transferase 
HGB 
Hemoglobin 
IGA 
Investigator’s global assessment 
IGA mod 2011 
Novartis Investigator’s Global Assessment modified 2011 
IRT 
Interactive response technology 
LLN 
Lower Limit of Normal 
MACE 
Major Adverse Cardiovascular Event 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Drug Regulatory Affairs 
NMQ 
Novartis MedDRA Query 
NovDTD 
Novartis Drug and Therapy Dictionary 
PASI 
Psoriasis Area and Severity Index 
PD 
Protocol deviation 
 
 
PT 
Preferred Term 
RMP 
Risk Management Plan 
SAS 
Statistical analysis software 
SAE 
Serious adverse event 
SOC 
System Organ Class 
TEAE 
Treatment Emergent Adverse Event 
ULN 
Upper Limit of Normal 
WBC 
White blood cell 
 








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Secondary 
To demonstrate the efficacy of secukinumab 300 mg every 2 weeks in 
comparison to secukinumab 300 mg every 4 weeks with respect to 
Investigator’s Global Assessment (IGA) mod 2011 0 or 1 response at 
Week 16. 
IGA mod 2011 response at 
Week 16 
To investigate the clinical safety and tolerability of secukinumab 300 mg 
every 2 weeks in comparison to secukinumab 300 mg every 4 weeks 
Vital signs, clinical laboratory 
variables, ECGs, Adverse 
Events. 
2 
Statistical methods 
Novartis will be performing the analysis. Statistical software SAS version 9.4 or later will be 
used. 
2.1 
Data analysis general information 
Summary statistics for continuous variables will include N, mean, standard deviation, minimum, 
lower quartile, median, upper quartile, maximum. Summary statistics for discrete variables will 
be presented in contingency tables and will include absolute and relative frequencies. 
If not otherwise specified, p-values will be presented as one-sided for hypotheses testings and 
as two-sided for other analysis. The level of significance will be set to 2.5% (one-sided, family-
wise type-I-error). 95% confidence intervals will be displayed but not be used for decision 
making; they will only be used for estimation and will therefore always be two-sided. 
All listings will be presented by treatment sequence. 
Footnotes on outputs will be kept to a minimum also for outputs not covered in 
 
. 
Footnotes will generally be provided for 
•
abbreviations used in the output; abbreviations used on several outputs, e.g. for listings in
Appendix 16.2 can be presented on a separate page and do not have to be repeated as
footnotes on each listing
•
sorting order of categories, e.g. for sorting within MedDRA (Medical Dictionary for
Regulatory Activities) hierarchy levels


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• MedDRA version used for reporting of MedDRA coded data 
Footnotes will generally NOT be given for 
• units displayed on the output 
• interpretation of results (e.g. “odds ratio larger 1 favors active treatment”) 
• information that can be retrieved from the statistical section of the clinical study report 
(CSR) unless it is not identifiable from the output, e.g. 
• explanation of analysis model used unless results of more than one model are 
displayed on an output 
• derivations of variables (e.g. BMI will not be explained on a footnote) 
• information that will be provided in the clinical study protocol and/or methods section of 
the CSR (e.g. baseline definition if this is specified in the statistical section of the CSR) 
2.1.1 
General definitions  
2.1.2 
Study treatment 
Novartis will supply the investigational therapy as follows: 
• Secukinumab 150 mg solution for sub-cutaneous injection in a 1 ml pre-filled syringe 
• Placebo solution for sub-cutaneous injection in a 1 ml pre-filled syringe 
2.1.3 
Study Day 1 and other study days 
The first day of administration of randomized study treatment (first dose) is defined as Study 
Day 1 or Day 1.  
All other study days will be labeled relative to Day 1. For event dates on or after Day 1, study 
day for a particular event date is calculated as [Date of event] – [Date of first dose]+1, i.e., Day 
2, Day 3, etc., will be one day, two days, etc., after Day 1, respectively. For the dates before 
Day 1, study day for an event date is calculated as [Date of event] – [Date of first dose], i.e., 
Day -1, Day -2, etc., will be one day, two days, etc., before Day 1, respectively. Duration of an 
event will be calculated as (Event end date – Event start date + 1). 
The descriptor “Day 0” will not be used. 
2.1.4 
Screening, baseline and post-baseline definitions 
Screening refers to any procedures (e.g., checking inclusion and exclusion criteria) performed 
prior to the date of first dose of study treatment (for safety analysis) or prior to the randomization 
date (for efficacy analysis). Per protocol, subject informed consent must be obtained prior to 
performing any study related activity. The date of signing informed consent is the start date of 
screening period. Any assessment obtained during the screening period will be labeled 
screening assessment. Assessments made on Day 1 may occur before or after the randomization 
or the first dose.  
For efficacy analyses, baseline is the last assessment (including unscheduled visits) obtained on 
or before the randomization day. All assessments obtained after randomization are considered 
as post-baseline unless otherwise specified. 


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For safety analyses, baseline is the last assessment (including unscheduled visits) obtained on 
or before the first dose day of study treatment. All assessments obtained after the first dose of 
study treatment are considered as post-baseline unless otherwise specified. 
2.1.5 
Day of last dose of randomized study treatment 
The date of last dose will be collected via the CRF. The subject’s exposure will be calculated 
considering the end of study period visit (including follow-up visits F4, F8) or last dose day 
+84 days whichever occurs earlier.  
On-treatment is defined as assessments within last dose plus 84 days. 
2.2 
Analysis sets 
The following analysis sets will be used for the data analysis. Rules of exclusion criteria of 
analysis is detailed in Section 5.5  
Randomized set: The randomized set will be defined as all subjects who were randomized at 
baseline visit. Unless otherwise specified, subjects misrandomized subjects will be excluded 
from the randomized set.  
Misrandomized subjects are subjects who are screen-failures, but have been randomized by the 
investigator before eligibility was finally assessed, however have not been treated.  
If subjects were re-screened and successfully randomized, they will be included in the 
randomized set according to the treatment assigned in the last randomization.  
Full analysis set (FAS): The FAS will be comprised of all subjects from the randomized set to 
whom study treatment has been assigned. Following the intent-to-treat principle, subjects will 
be analyzed according to the treatment assigned to at randomization.  
Of note, subjects excluded from the randomized set will be excluded from the FAS. 
Safety set: The safety set includes all subjects who took at least one dose of study treatment 
during the treatment period. Subjects will be analyzed according to treatment received.  
The treatment received will be set to the treatment randomized. But if a subject has received the 
wrong treatment during the entire study, the treatment received will be set to this wrong 
treatment.  
2.2.1 
Subgroup of interest 
No subgroup analysis is planned for this study. 
2.3 
Patient disposition, demographics and other baseline 
characteristics 
2.3.1 
Patient disposition 
The number of subjects screened will be presented. In addition, the reasons for screen failures 
will be provided. The number and percentage of subjects in the randomized set who completed 
study periods, and who discontinued the study prematurely (including the reason for 


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discontinuation), will be presented by treatment period 1,  treatment period 2, entire treatment 
period and entire study period for each treatment group and all subjects. 
For each protocol deviation, the number and percentage of subjects for whom the deviation 
applies will be tabulated. Additional listing for protocol deviations due to COVID 19 will be 
presented separately. 
The patient disposition will be shown for below treatment groups: 
The patient disposition will be shown for below treatment groups: 
• for treatment period 1: 
• AIN457 300 mg Q2W 
• AIN457 300 mg Q4W 
• Total 
 
 
 
 
 
 
 
 
• Entire treatment period and Entire study period: 
• AIN457 300mg Q2W 
• AIN457 300mg Q4W (in Randomization Process) [AIN457 300 mg (eff)] 
 
 
 
 
• Total 
2.3.2 
Demographics and baseline characteristics 
The following common background and demographic variables will be analyzed: 
Continuous variables: 
o Age  
o Height 
o Weight 
o Body mass index (BMI) 
Categorical variables: 
o Age categories (<65 years, 65 years and older, 75 years and older) 
o Gender 
o Race 
o Ethnicity 
o Smoking status at baseline 
Psoriasis specific baseline characteristics and history of disease will be summarized as well: 
baseline PASI, baseline PASI (≤20, >20), baseline total BSA, baseline IGA mod 2011 score (at 


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least mild, moderate, severe), severity of psoriasis (CHMP guidelines, mild (total BSA <10% 
and PASI < 10), moderate ((PASI ≥10 or total BSA≥10%) and PASI ≤20 and total BSA ≤20%), 
severe (total BSA >20% or PASI > 20)), psoriatic arthritis (yes, no), time since diagnosis of 
psoriasis, time since diagnosis of psoriatic arthritis, previous exposure to biologic systemic 
psoriasis therapy, previous exposure to systemic psoriasis therapy, previous exposure to non-
biologic systemic psoriasis therapy, previous failure to biologic systemic psoriasis therapy, 
previous failure to systemic psoriasis therapy, previous failure to non-biologic systemic 
psoriasis therapy.  
Body Mass Index (BMI) will be calculated using the following formula: 
BMI = (body weight in kilograms) / (height in meters)2 
For BMI, height and body weight the last value prior to randomization is used. If there is no 
weight recorded prior to taking of study treatment, BMI will be missing. 
Of note: subject’s height will not be remapped according to the analysis visit window. 
Time since diagnosis of psoriasis (PsO) and time since diagnosis of psoriatic arthritis (PsA) will 
be calculated using the following formula: 
Time since diagnosis = (inform consent date –first diagnosis date + 1)/365.25 
The first diagnosis date of PsO or PsA will be imputed according to the imputation rules in 
Section 5.1.3.3 
Unless otherwise specified, summary statistics will be presented for continuous variables for 
each treatment group and for all subjects (total) in the randomized set. The number and 
percentage of subjects in each category will be presented for categorical variables for each 
treatment group and all subjects (total) in the randomized set. 
Any condition entered on the Relevant medical history / current medical conditions CRF will 
be coded using the MedDRA dictionary. They will be summarized by System Organ Class 
(SOC) and Preferred Term (PT) of the MedDRA dictionary. 
Summaries for cardiovascular medical history will be summarized by categories.  
Smoking history will be summarized by treatment group. 
Treatment groups defined in Section 2.3.1 will be used as appropriate. 
2.4 
Treatments (study treatment, rescue medication, concomitant 
therapies, compliance) 
2.4.1 
Study treatment / compliance 
The analysis of study treatment data will be based on the safety set. 
The number of secukinumab and secukinumab placebo will be summarized by treatment group 
by means of contingency tables. 
The duration of exposure to study treatment will be summarized by treatment group. In addition, 
the number of subjects with exposure of at least certain time thresholds will be displayed. The 
following categories will be presented: “any exposure”, “≥1 week”, “≥2 week”,  “≥3 week” , 


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“≥4 weeks”, “≥8 weeks”, “≥12 weeks”, “≥16 weeks”, “≥20 weeks”, “≥24 weeks”, “≥28 weeks”, 
“≥32 weeks”, “≥40 weeks” and “≥52 weeks”. 
Duration of exposure will be defined as the time from first dose of study medication to the last 
dose plus 84 days or last visit (including follow-up visits) whichever occurs earlier. i.e., for 
subjects who discontinued or have their last visit earlier than 84 days, the end of study treatment 
exposure will be the date of the last study visit in the follow-up period or in the corresponding 
treatment period. 
Duration of exposure (days) = min (‘end of treatment period’ date, last dose date +84) – first 
dose date +1 
Duration of exposure (years) = duration of exposure (days) / 365.25s 
Duration of exposure (100 subject years) = duration of exposure (years) / 100 
2.4.2 
Visit window 
Visit-windows will be used for the data that is summarized by visit; they are based on the study 
evaluation schedule and comprise a set of days around the nominal visit day. For any assessment, 
there are the protocol defined scheduled visits around which visit windows were created to 
cover the complete range of days within the study. The visit windows are shown in Table 2-1. 
In this table, the days are counted since the first dose of study treatment (study days) for safety 
assessments, and the days are counted since the date of randomization for efficacy assessments. 
These visit windows apply to measurements taken at every visit. For assessments collected less 
often different visit windows will be applied as detailed below. 
When visit windows are used, all visits will be re-aligned, i.e., they will be mapped into one of 
the visit windows. E.g., if the Week 4 visit of a subject is delayed and occurs on Day 60 instead 
of on Day 29, it will be re-aligned to visit window Week 8. In the case of major deviations from 
the visit schedule, or due to unscheduled visits, several assessments of a subject may fall in a 
particular visit window (either scheduled or unscheduled). Statistical approaches to handle 
multiple assessments in a given visit window are specified below. 
Table 2-1 
Assessment windows for scheduled visits  
Analysis Visit 
Week 
Scheduled Day 
Visit Window 
Baseline 
BSL 
1 
-28 days to Day 1* 
Week 1 
1 
8 
Day 2-11 
Week 2 
2 
15 
Day 12-18 
Week 3 
3 
22 
Day 19-25 
Week 4 
4 
29 
Day 26-43 
Week 8 
8 
57 
Day 44-71 
Week 12 
12 
85 
Day 72-99 
Week 16 
16 
113 
Day 100-127 


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Week 20 
20 
141 
Day 128-155 
Week 24 
24 
169 
Day 156-183 
Week 28 
28 
197 
Day 184-211 
Week 32 
32 
225 
Day 212-253 
Week 40 
40 
281 
Day 254-323 
Week 52 
52 
365 
Day 324-379 
Week 56 (F4) 
56 
393 
Day 380-407 
Week 60 (F8) 
60 
421 
Day 408-435 
* Baseline measurement before the first drug administration for safety assessments and before 
the randomization for efficacy assessments. 
For parameters which are not collected at every visit (e.g. weight, laboratory, 
), visit 
windows defined in Table 2-1 will be combined. For example, if a parameter is measured at 
Week 12 and Week 28 only, Week 12 visit window will extend from Day 2 to Day 99 
(combining Week 1 to Week 12 visit windows), Week 28 will extend from Day 100 to Day 211 
(combining Week 16 to Week 28). For safety parameters which are not collected after week 52 
(e.g. ECG), upper limit will be extended to last day of study i.e. Day 435 and only ‘on-treatment’ 
events will be consider for analysis. If more than one assessment falls into the interval, the rules 
defined in Section 2.4.3 below are applied. 
The analysis visit will be used for listing of visit and period for both safety and efficacy data. If 
a visit falls after the last visit window (after Day 435) it is not assigned an analysis visit and 
will be listed under label “After Week 60”. 
2.4.3 
Multiple assessments within visit windows 
When there are multiple assessments in a particular visit window, the following rules are applied 
to select one value “representing” the subject in summary statistics in a visit window (See Table 
2-1). 
For baseline assessment definition see Section 2.1.4. For post-baseline visit windows the 
following applies (unless otherwise specified): 
• for quantitative variables, the closest to the actual visit is chosen (if two assessments have 
the same distance, then the earlier one will be chosen);  
• for qualitative variables, the worst record is selected. It is noted that in the analyses 
performed, worst case is always well defined (e.g., for urine protein values “+” and “++”, 
the worst case is defined as “++”), 
• in case qualitative variables are based on quantitative variables, e.g. PASI 90 response, the 
visit will be assigned to the quantitative variable, and this visit will be used for the derived 
qualitative variable.  




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Prior medications are defined as drugs taken and stopped prior to the first dose of study 
treatment. Any medication given at least once between the day of first dose of randomized study 
treatment, and last dose plus 84 days or last study visit (including follow-up visits) whichever 
occurs earlier will be a concomitant medication, including those which were started pre-
baseline and continued into the treatment period.  
Psoriasis specific summaries of prior and/or concomitant medication will be presented as in 
Table 2-3, but as well for topical, phototherapy and photochemotherapy (yes/no) using the 
randomized set. 
In addition, medical procedures and significant non-drug therapies as coded in MedDRA will 
be summarized. 
Prior or concomitant medication will be identified based on recorded or imputed start and end 
dates of medication taken. Further rules will be given in Section 5. 
Table 2-3 
Summary of previous psoriasis therapy 
Level 1 
description 
Level 1 outcome 
Level 2 description 
Level 2 outcome 
 
previous therapy 
yes/no 
systemic 
No 
Yes 
number 
1 
2 
>=3 
failure* 
no 
yes 
biologic 
No 
Yes 
failure* 
no 
yes 
type of previous biologic 
anti-p40 
no 
yes 
 
anti-TNF 
no 
yes 
 
non-biologic systemic 
No 
Yes 
failure* 
no 
yes 
failure* to at least 2 
no 
yes 
*: at least one therapy with lack of primary efficacy or lack of secondary efficacy or lack of tolerability 
2.5 
Analysis of the primary objective 
The study objectives are defined as in study protocol Section 2.1. 
Treatment arms defined for efficacy analysis:  
• Primary and secondary endpoint of PASI 90 and IGA 0/1 response at Week 16:  
• AIN457 300mg Q2W 


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• AIN457 300mg Q4W  
2.5.1 
Primary endpoint 
The primary endpoint is PASI 90 response at week 16. The analysis of primary variable will be 
based on FAS. 
2.5.2 
Definition of PASI and related variables 
The investigator or trained qualified designee will complete the PASI assessments. Whenever 
possible, the same evaluator should perform this assessment at all visits. 
The total BSA affected by plaque-type psoriasis will be estimated from the percentages of areas 
affected, including head, trunk, upper limbs and lower limbs (see below for PASI assessment). 
The following calculations will be done: each reported percentage will be multiplied by its 
respective body region corresponding factor (head = 0.1, trunk = 0.3, upper limbs = 0.2, lower 
limbs = 0.4). The resulting 4 percentages will be added up to estimate the total BSA affected 
by plaque-type psoriasis. The PASI scoring system is further described in Table 2-4. 
A PASI score (Fredriksson and Pettersson 1978, Weisman et al 2003, Gottlieb et al 2005) will 
be derived as indicated in Table 2-4. The head, trunk, upper limbs and lower limbs are assessed 
separately for erythema, thickening (plaque elevation, induration), and scaling (desquamation). 
The average degree of severity of each sign in each of the four body regions is assigned a score 
of 0-4. The area covered by lesions on each body region is estimated as a percentage of the total 
area of that particular body region. Further practical details help the assessment: 
1. The neck is assessed as part of the head. 
2. The axillae and groin are assessed as part of the trunk. 
3. The buttocks are assessed as part of the lower limbs. 
4. When scoring the severity of erythema, scales should not be removed. 
Because the head and neck, upper limbs, trunk and lower limbs correspond to approximately 
10%, 20%, 30% and 40% of the body surface area, respectively, the PASI score will be 
calculated using the formula: 
PASI = 0.1 (Eh + Ih + Dh)Ah + 0.2 (Eu + Iu + Du)Au + 0.3 (Et + It + Dt)At + 0.4 (El + Il + Dl)Al, 
where E, I, D, and A denote erythema, induration, desquamation, and area, respectively, and h, 
u, t, and l denote head, upper extremities, trunk, and lower extremities, respectively (see Table 
2-4). 




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• PASI 90 response: subjects achieving ≥ 90% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 90 responders 
 
 
2.5.3 
Definition of IGA mod 2011 score and IGA mod 2011 0 or 1 response 
The IGA mod 2011 rating scale for overall psoriatic disease (shown in Table 2-5) has been 
developed based on a previous version of the scale used in secukinumab phase II studies, and 
has been updated in collaboration with health authorities (in particular the FDA). The 
explanations/descriptions of the points on the scale have been improved to ensure appropriate 
differentiation between the points. It is recommended that the same evaluator conducts the 
assessments throughout the study whenever possible. 
The IGA mod 2011 used in this study is static, i.e., it refers exclusively to the subject’s disease 
state at the time of the assessments, and does not attempt a comparison with any of the subject’s 
previous disease states, whether at baseline or at a previous visit. 
Table 2-5 
The IGA mod 2011 rating scale 
Score 
Short Description 
Detailed Description 
0 
Clear 
No signs of psoriasis. Post-inflammatory hyperpigmentation may 
be present. 
1 
Almost clear 
Normal to pink coloration of lesions; no thickening; no to minimal 
focal scaling. 
2 
Mild 
Pink to light red coloration; just detectable to mild thickening; 
predominantly fine scaling. 
3 
Moderate 
Dull bright red, clearly distinguishable erythema; clearly 
distinguishable to moderate thickening; moderate scaling. 
4 
Severe 
Bright to deep dark red coloration; severe thickening with hard 
edges; severe / coarse scaling covering almost all or all lesions. 
Note:  Involvement of nails is not part of the assessment. 
Subjects require an IGA mod 2011 score at randomization of 3 or 4 in order to participate in 
the study. Based on this scale, subjects will be considered as IGA mod 2011 0 or 1 responder 
if they achieve a score of 0 or 1 and improve by at least 2 points on the IGA mod 2011 scale 
compared to baseline. 
2.5.4 
Statistical hypothesis, model, and method of analysis 
The statistical hypothesis for PASI 90 response at Week 16 is that AIN457 300mg Q2W is not 
superior to AIN457 300mg Q4W in the proportion of subjects with PASI 90 response at Week 
16. 
  
  
 
 
 
 
The following hypotheses will be tested: 


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H1: p1 – p0 ≤ 0 versus HA1: p1 – p0 > 0, 
In other words: 
H1: AIN457 300mg Q2W is not superior to AIN457 300mg Q4W with respect to PASI 90 
response at Week 16 
The primary analysis method for PASI 90 at Week 16 will be evaluated using logistic regression 
model with treatment group, baseline body weight and baseline PASI score as explanatory 
variables (see Section 5 Appendix). Odds ratios will be computed for comparisons of AIN457 
300mg Q2W versus AIN457 300mg Q4W utilizing the logistic regression model fitted. In case 
of non-convergence, for analyses with multiple imputation, confidence intervals for risk 
difference and p-values from the t-test for the risk difference comparing to 0 will be provided; 
for analyses with non-responder imputation, Fisher’s exact test will be performed and 
confidence intervals for risk difference will be provided. 
The hypotheses H1 will be tested at level 2.5% (one-sided). 
Details in primary analysis is provided in Section 5.4.1.1 and the sensitivity analysis are 
provided in Section 2.5.6 
2.5.5 
Handling of missing values/censoring/discontinuations 
Response variables based on PASI score and IGA mod 2011 categories will be imputed with 
multiple imputation (MI) as primary imputation method for the missing values (refer to Section 
5.4.1.2). 
Multiple imputation (MI) is a simulation based approach where missing values are replaced by 
multiple Bayesian draws from the conditional distribution of missing data given the observed 
data and covariates, creating multiple completed data sets. These completed data sets can then 
be analyzed using standard methods. Within this analysis the PASI score or IGA mod 2011 
categories will be imputed and response variables will be derived based on the imputed scores. 
In the multiple imputation analysis the response status will be imputed based on the individual 
treatment arm information. 
2.5.6 
Supportive analyses 
Primary variable and key secondary variable will be evaluated using logistic regression as 
described in primary analysis method with modified non-responder (mNRI) imputation as a 
sensitivity method. 
Missing values with respect to response variables based on PASI score and IGA 2011 categories 
will be imputed with non-response regardless to the reason for missing data (e.g. premature 
study discontinuation, missed visit, administrative issues). Exceptions for modified non-
responder imputation method will apply to the following: 
• If a subject dropped out of the study prior to last scheduled visit and being responder 
consecutively at least for two preceding visits, the subject will be imputed as 
responder for the last scheduled visit. 
• If a subject who was responder at visit x-1 and visit x+1 but has missing data at visit x, 
then the subject will be imputed as responder for visit x only if visit x-1 or visit x+1 are 


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scheduled 4 weeks or less from visit x. Otherwise missing data at visit x will be imputed 
with non-response, except for the missing data at last visit in the treatment period. 
2.6 
Analysis of the key secondary objective 
2.6.1 
Secondary endpoint 
The secondary variable in testing strategy is the IGA mod 2011 0 or 1 response at Week 16 
(for superiority comparison of AIN457 300 mg Q2W versus AIN457 Q4W). The IGA mod 
2011 0 or 1 response at Week 16 will be analyzed analogously to PASI 90 response at Week 
16 (i.e., logistic regression analysis). 
The analysis of secondary variable will be based on FAS. 
2.6.2 
Statistical hypothesis, model, and method of analysis 
H2: AIN457 300mg Q2W is not superior to AIN457 300mg Q4W with respect to IGA mod 
2011 0 or 1 response at Week 16 
Testing Strategy  
 
The family-wise type-I-error will be set to α=2.5% (one-sided). The graphical approach of 
Bretz (Bretz et al 2009) for sequentially rejective testing procedures is used to illustrate the 
hierarchical testing strategy. 
One-sided p-values will be derived. Each hypothesis is tested sequentially at α=2.5% (one-
sided). 
The testing sequence will continue to H2 at α (one-sided) only if H1 has been rejected. 
2.6.3 
Handling of missing values/censoring/discontinuations 
See Section 2.5.5. 
2.7 
Analysis of secondary efficacy objective(s) 
No other secondary efficacy objectives were analyzed. 


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2.7.1 
Secondary endpoints 
Not applicable. 
2.7.2 
Statistical hypothesis, model, and method of analysis 
Not applicable. 
2.7.3 
Handling of missing values/censoring/discontinuations 
Not applicable. 
2.8 
Safety analyses 
All safety analyses will be based on the safety set. Only those visits which were pre-planned in 
the protocol will be reported in tables and figures for safety variables. 
Treatment groups for safety evaluation 
Treatment period 1:  
• AIN457 300mg Q2W 
• AIN457 300mg Q4W 
• Any AIN457 dose (Total) 
Entire study period:  
• AIN457 300mg Q2W 
• AIN457 300mg contineous Q4W 
 
 
 
  
• Any AIN457 dose (Total) 
Safety analyses will be performed on treatment received or actual treatment (See Section 
5.4.2, Safety Set). 
2.8.1 
Adverse events (AEs) 
For adverse events and other binary safety variables crude incidence will be derived as 
described below.  
All adverse events are summarized based on treatment emergent only. The definition for 
“treatment emergent” is as below: 
• events started after the first dose of study medication or events present prior to the first 
dose of study medication but increased in severity based on preferred term  
• and started prior to the last dose plus 84 days (inclusive)  
All adverse events will be listed with “treatment emergent” flag displayed. 


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The crude incidence of treatment emergent adverse events will be summarized by primary 
System Organ Class (SOC) and Preferred Term (PT). Confidence intervals for the crude rate 
will be derived using the score method including continuity correction (Newcombe 1998) as 
described in Section 5.4.2.1.  
Adverse events will be summarized by presenting, for each treatment group, the number and 
percentage of subjects having at least one AE, having an AE in each primary system organ class 
and having each individual AE (preferred term). Summaries will also be presented for AEs by 
severity and for study treatment related AEs. If a particular AE ‘severity’ is missing, this 
variable will be listed as missing and treated as missing in summaries. If a subject reported more 
than one adverse event with the same preferred term, the adverse event with the greatest severity 
will be presented. If a subject reported more than one adverse event within the same primary 
system organ class, the subject will be counted only once with the greatest severity at the system 
organ class level, where applicable.  
Adverse events will also be summarized by standardized or customized MedDRA queries 
(SMQ or CMQ/NMQ). The MedDRA version used for reporting the adverse events will be 
described in a footnote. 
The most common adverse events reported (≥ z % in any group for each preferred term in the 
table by SOC and PT or ≥ z % in any group for each grouping term table) will be presented in 
descending frequency according to its incidence in secukinumab group starting from the most 
common event. Here threshold value z is set to 2 (%) but it may be updated following review 
of the dry run outputs. 
Separate summaries will be provided for deaths, serious adverse events, other significant 
adverse events leading to discontinuation and adverse events leading to dose adjustment or 
interruption. 
Algorithms for date imputations will be provided in Section 5. 
For SAEs occurred during screening a listing will be prepared for all subjects screened including 
screening failures.The adverse events occurred after the treatment errors in those subjects who 
received erroneously the wrong treatment at least once, will be listed. 
2.8.2 
Adverse events of special interest / grouping of AEs 
Crude incidence rate for adverse events of special interest will be provided as in Table 2-6. 
Table 2-6 
AEs of special interest 
Special AE interest: 
Notes (All levels are displayed) 
Inflammatory bowel disease [STANDARD](NMQ) (narrow) 
Include Crohns (PT) and Ulcerative colitis 
(PT) and others 
Opportunistic infections [FINGOLIMOD](NMQ) 
Candida infections (HLT) 
Herpes viral infections (HLT) 
Both Oral and other are included 
Staphylococcal infections (HLT) 
MACE (MI, Stroke, Cardiovascular death) [AIN457](NMQ) 
Malignant or unspecified tumours (SMQ) 
Including BCC, SCC in SMQ 


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Malignant or unspecified tumours (SMQ excl BCC and SCC) 
[AIN457](NMQ) 
Upper respiratory tract infections (HLT) 
Other safety topics of interest, such as risks defined in the Risk Management Plan or topics of 
interest regarding signal detection or routine analysis are defined in the Program Case Retrieval 
Sheet that is stored in GPS at the path 
. 
Crude rate of important identified and potential risks from Case Retrieval Sheet will be provided 
for all (non-serious and serious) cases and for all serious cases.  
Risk measures and confidence intervals will be derived according to Section 5. 
The version of the Case Retrieval Sheet used for the analyses will be described in a footnote. 
This includes MedDRA version and Novartis MedDRA Query (NMQ) dictionary date.  
Important note: For the evaluation of risks primary and secondary system organ classes of the 
MedDRA dictionary will be considered. 
2.8.3 
Deaths 
Separate summary and listing will be provided for deaths. 
2.8.4 
Laboratory data 
The summary of laboratory evaluations will be presented for two groups of laboratory tests 
(hematology and serum chemistry).  
Descriptive summary statistics for the change from baseline to each study visit will be presented 
by laboratory test and treatment group. Change from baseline will only be summarized for 
subjects with both baseline and post baseline values and will be calculated as: 
change from baseline = post baseline value – baseline value 
Only “on-treatment” laboratory data will be summarized (i.e. assessments within last dose plus 
84 days). All laboratory data will be listed with “on-treatment” flag displayed. If two 
measurements are taken on the same date/time/CRF visit then use the average of two 
assessments. 
For laboratory test values below Lower Level of Quantification (LLQ) or above Upper Level 
of Quantification (ULQ) will be imputed as LLQ or ULQ value, respectively. The numerical 
part of the reported result will be treated as the actual LLQ or ULQ. These laboratory values 
will be displayed in listings using the standard unit with the reported sign (“<” or “>”).” 
In addition, shift tables will be provided for all parameters to compare a subject’s baseline 
laboratory evaluation relative to the most extreme laboratory test value within a treatment 
period. For the shift tables, the normal laboratory ranges will be used to evaluate whether a 
particular laboratory test value is normal, low, or high (including category “high and low”). 
These summaries will be presented by laboratory test and treatment group. Subjects with 
abnormal laboratory values will be listed and values outside the normal ranges will be flagged. 
The following laboratory parameters will be analyzed with respect to numerical Common 
Terminology Criteria for Adverse Events (CTCAE) grades, given in Table 2-7: hemoglobin, 
platelets, white blood cell count, neutrophils, lymphocytes, creatinine, total bilirubin (TBL), 


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gamma-glutamyl 
transferase 
(GGT), 
alanine 
aminotransferase 
(ALT), 
aspartate 
aminotransferase (AST), alkaline phosphatase (ALP). 
The number and percentage of subjects with CTCAE grade newly occurring or worsening after 
baseline will be presented. These summaries will be split into hematology and chemistry. 
Table 2-7 
CTCAE grades for laboratory parameters to be analyzed 
CTCAE v4.0 Term 
Grade 1    
Grade 2    
Grade 3    
Grade 4    
HGB decreased 
(Anemia) 
<LLN – 100 g/L 
<100 – 80 g/L 
<80 g/L  
Life-threatening 
consequences; 
urgent 
intervention 
Platelet count 
Decreased 
<LLN – 75.0 x10e9 /L 
<75.0 - 50.0 x10e9 /L 
<50.0 – 25.0 x10e9 /L 
<25.0 x 10e9 /L 
White blood cell 
decreased 
<LLN - 3.0 x 10e9 /L 
<3.0 - 2.0 x 10e9 /L 
<2.0 - 1.0 x 10e9 /L 
 
<1.0 x 10e9 /L 
Neutrophil count 
decreased 
<LLN - 1.5 x 10e9 /L 
<1.5 - 1.0 x 10e9 /L 
<1.0 - 0.5 x 10e9 /L 
<0.5 x 10e9 /L 
Lymphocyte count 
decreased 
<LLN - 0.8 x 10e9/L 
<0.8 - 0.5 x 10e9 /L 
<0.5 - 0.2 x 10e9 /L 
<0.2 x 10e9 /L 
Creatinine increased 
>ULN - 1.5 x ULN 
>1.5 - 3.0 x ULN 
>3.0 - 6.0 x ULN 
>6.0 x ULN 
TBL increased 
>ULN - 1.5 x ULN 
>1.5 - 3.0 x ULN 
>3.0 - 10.0 x ULN 
>10.0 x ULN 
GGT increased 
>ULN - 2.5 x ULN 
>2.5 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
ALT increased 
>ULN - 3.0 x ULN 
>3.0 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
AST increased 
>ULN - 3.0 x ULN 
>3.0 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
ALP increased 
>ULN - 2.5 x ULN 
>2.5 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
Amylase increased 
>ULN – 1.5 x ULN 
> 1.5 -2.0 x ULN 
>2.0 – 5.0 x ULN 
> 5.0 x ULN 
Lipase increased 
>ULN – 1.5 x ULN 
> 1.5 -2.0 x ULN 
>2.0 – 5.0 x ULN 
> 5.0 x ULN 
 
 
 
 
 
Shift tables will be presented comparing baseline laboratory result (CTCAE grade) with the 
worst results (expressed in CTCAE grade) during the treatment phase analyzed. Of note, 
baseline will be defined as last assessment prior to first dosing in initial treatment phase. If no 
pre-treatment value exists, also a value recorded after first dose can be used as baseline if it was 
collected on the same day as first dose, see Section 2.1.3. 
The number and percentage of subjects with newly occurring liver enzyme abnormalities will 
also be summarized based on the event criteria given in Table 2-8. 


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Table 2-8 
Liver-related events 
Parameter 
Criterion 
ALT 
>3xULN; >5xULN; >8xULN;>10xULN, >20xULN 
AST 
>3xULN; >5xULN; >8xULN; >10xULN; >20xULN 
ALT or AST 
>3xULN; >5xULN; >8xULN; >10xULN; >20xULN 
 
TBL 
>1xULN;>1.5xULN; >2xULN; >3xULN, 
ALP 
>1.5xULN;>2xULN; >3xULN; >5xULN 
ALT or AST & 
TBL 
ALT or AST>3xULN & TBL >1.5xULN; 
ALT or AST>3xULN & TBL >2xULN; 
ALT or AST >5xULN & TBL >2xULN; 
ALT or AST >8xULN & TBL >2xULN; 
ALT or AST >10xULN & TBL >2xULN; 
ALT or AST >20xULN & TBL >2xULN; 
ALP & TBL 
ALP >3xULN & TBL >2xULN 
ALP >5xULN & TBL >2xULN 
ALT or AST & 
TBL & ALP 
ALT or AST>3xULN & TBL >2xULN & ALP <2xULN  (Potential Hy’s Law) 
Note: elevated ALP may suggest obstruction as a consequence of gall bladder or 
bile duct disease; ALP may also be increased in malignancy. FDA therefore terms 
Hy’s Law cases as indicators of pure hepatocellular injury. This does not mean 
that cases of ALT or AST >3xULN & TBL >2xULN & ALP >2xULN may not result 
in severe DILI. 
ALT or AST>3xULN & TBL >2xULN & ALP <2xULN  (Potential Hy’s Law) or 
reported Hy’s Law case 
Note: “Hy’s Law case” is a lower level term in MedDRA (10070546) and may be 
reported as AE. 
For a combined criterion to be fulfilled, all conditions have to be fulfilled on the same visit. The 
criteria are not mutually exclusive, e.g., a subject with ALT = 6.42xULN is counted for 
ALT >3xULN and ALT>5xULN. 
Individual subject data listings will be provided for subjects with notably abnormal laboratory 
values (reference to Protocol Amendment 1, Appendix 1) and newly occurring or worsening 
abnormal laboratory data by CTC grades. Data of subjects with newly occurring liver enzyme 
abnormalities will be listed in an additional listing. 
Fasting laboratory tests including fasting plasma glucose and fasting lipids will be evaluated 
only at screening. No analysis will be done for these measurements. 
For urinalysis, standard dipstick measurements for specific gravity, protein, glucose, pH, blood, 
urine blood (non-hemolyzed), urine blood (hemolyzed), bilirubin, ketones, WBC will be done 
at screening. No analysis will be done for these measurements. 
2.8.5 
Other safety data 
 
 
 


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2.8.5.2 
ECG  
Number and percentage of patients with notable abnormal ECG result will be summarized for 
entire treatment period. Summary statistics will be presented for ECG variables by visit and 
treatment group. 
A listing of all newly occurring or worsening abnormalities will be provided. 
Notable abnormal is defined as: 
• QTcF > 450 msec  
• QTcF > 480 msec  
• QTcF > 500 msec  
• QTcF changes from baseline > 30 msec  
• QTcF changes from baseline > 60 msec  
• PR > 250 msec 
2.8.5.3 
Vital signs 
Analysis in vital sign measurement using descriptive summary statistics for the change from 
baseline for each post-baseline visit will be performed by vital sign and treatment group. 
Change from baseline will only be summarized for subjects with both baseline and post-baseline 
values and will be calculated as: 
change from baseline = post-baseline value – baseline value 
Only “on-treatment” vital signs will be summarized (i.e. assessments within last dose plus 84 
days). All vital signs will be listed with “on-treatment” flag displayed. 
The number and percentage of subjects with newly occurring notable vital signs will be 
presented. Criteria for notable vital sign abnormalities are provided in Table 2-9 below. A listing 
of subjects with newly occurring notably abnormal vital signs will be provided. 
Table 2-9 
Criteria for notable vital sign abnormalities 
Vital sign (unit) 
Notable abnormalities 
Systolic blood pressure (mmHg) 
>= 140 mmHg or < 90 mmHg 
Diastolic blood pressure (mmHg) 
>=90 mmHg or <60 mmHg 
Pulse (bpm) 
> 100 bpm or <60 bpm 


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2.14 
Interim analysis 
A Week 16 primary efficacy analysis will be conducted when the last patient complete his 
Week 16 visit. All the safety data up to this date will be summarized. Efficacy data up to 
Week 16 visit for each patients will be summarized. All data up to this date will be listed.  




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


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a. If the CM month is missing, the imputed CM start date is set to the mid-year point 
(01JulYYYY).  
b. Else if the CM month is not missing, the imputed CM start date is set to the mid-
month point (15MONYYYY).  
3. If the CM start date year value is greater than the treatment start date year value, the CM 
started after treatment. Therefore:  
a. If the CM month is missing, the imputed CM start date is set to the year start point 
(01JanYYYY).  
b. Else if the CM month is not missing, the imputed CM start date is set to the month 
start point (01MONYYYY).  
4. If the CM start date year value is equal to the treatment start date year value:  
a. And the CM month is missing or the CM month is equal to the treatment start date 
month, then the imputed CM start date is set to one day prior treatment start date.  
b. Else if the CM month is less than the treatment start date month, the imputed CM 
start date is set to the mid-month point (15MONYYYY).  
c. Else if the CM month is greater than the treatment start date month, the imputed CM 
start date is set to the month start point (01MONYYYY).  
If complete (imputed) CM end date is available and the imputed CM start date is greater than 
the (imputed) CM end date, then imputed CM start date should be set to the (imputed) CM 
end date.  
5.1.3.1 
Prior therapies date imputation 
See Section 5.1.3. 
5.1.3.2 
Post therapies date imputation 
See Section 5.1.3. 
5.1.3.3 
First diagnosis date (Pso, PsA) imputation 
1. If the first diagnosis day/ month are missing and the year is non-missing: 
a. If the year part of the first diagnosis date is equal to the year part of the inform 
consent date, then the imputed first diagnosis date is set to the year start point 
(01JanYYYY). 
b. Otherwise the imputed first diagnosis date is set to the mid-year point 
(01JulYYYY). 
2. If the first diagnosis day is missing and the month/year are non-missing: 
a. If the month and year part of the first diagnosis date is equal to the month and year 
part of the inform consent date, then the imputed first diagnosis date is set to the 
month start point (01MONYYYY). 
b. Otherwise the imputed first diagnosis date is set to the mid-month point 
(15MONYYYY). 




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Logistic regression will be applied to response variables at each visit. 
If logistic regression model does not converge the following steps will be performed: 
1. If convergence not reached, remove the covariates from the model one by one until 
convergence is reached; start with removing baseline body weight , followed by baseline 
PASI;  
2. If convergence not reached, perform Fisher’s exact test. 
It should be noted that this model might not converge if response rates are too low. 
5.4.1.2 
Multiple imputations for response variables  
Primary and secondary endpoints will be evaluated by Logistic regression and odds ratio 
estimate as described in the primary analysis method with multiple imputations for missing 
values. In addition, logistic regression analysis for 
, PASI 90, 
 and 
IGA mod 2011 0 or 1 response by visits will be analyzed using multiple imputation method. 
In the multiple imputations analysis the response status will be imputed based on the individual 
treatment arm information. 
Multiple imputation (MI) is a simulation based approach where missing values are replaced by 
multiple Bayesian draws from the conditional distribution of missing data given the observed 
data and covariates, creating multiple completed data sets. These completed data sets can then 
be analyzed using standard methods. Rubin (1987) presented rules how to combine the multiple 
sets of estimates to produce overall estimates and confidence intervals that adequately 
incorporate missing data uncertainty.  
Missing values for the ‘change from baseline PASI score’ and ‘IGA mod 2011 score’ will be 
imputed simultaneously based on an underlying joint normal distribution and using a Markov 
Chain Monte Carlo (MCMC) method. The change from baseline in PASI score appears to 
follow closer to a normal distribution than the actual PASI score. Assuming normality for the 
‘IGA mod 2011 score’ is motivated by Schaefer (1997), where it was shown that the 
multivariate normal approximation for the imputation of incomplete categorical and binary data 
is robust.  
The imputations will be done separately for each treatment group including baseline weight, 
failure to at least one previous biologic (yes/no), and number of previous systemic therapies as 
additional covariates.  
Summary statistics for 
, PASI 90, 
 and IGA mod 2011 0 or 1 
response by visit will be presented in contingency tables with multiple imputations method. 
The number of imputations will be set to 100, the seed for the random function will be set to 
4572326 for this study. To generate the multiple imputed data sets, the SAS procedure MI can 
be used as follows: 
The input data set <pasi_iga> should have one record per subject with baseline PASI score and 
IGA mod 2011 score as well as all changes from baseline PASI and post-baseline IGA mod 
2011 score. 
 
ODS LISTING CLOSE; 


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ODS OUTPUT MissPattern=msgpat VarianceInfo=varinfo ParameterEstimates=param; 
PROC MI DATA=<pasi_iga> OUT=<impdata> SEED=457<studycode> NIMPUTE=100; 
 VAR <baseline weight> <failure to at least one biologic>  
     <number of previous systemic therapies>  
     <baseline PASI> <baseline IGA>  
     <change from baseline PASI week 1> - <change from baseline PASI week primary endpoint> 
     <IGA week1> - <IGA week primary endpoint>; 
  BY <treatment group>; 
RUN; 
ODS LISTING; 
 
Programming notes: 
• The SAS procedure MIANALYZE expects a variable called “_IMPUTATION_ which 
is generated by the MI procedure. It might be needed to set the SAS option 
“VALIDVARNAME=UPCASE” temporarily in the program before the MI call, this 
option should be reset after the MIANALYZE call to VALIDVARNAME=V6.  
• In case there are no missings in one treatment group, the MI procedure does not 
impute any values. In this case the corresponding data need to be imputed manually 
outside PROC MI and added to the dataset <impdata>. 
 
The imputed data are saved in data set <impdata>. The outcomes of interest, i.e. the PASI 
/90/
 response and IGA mod 2011 0 or 1 response will be calculated, e.g. as follows: 
 
DATA <impdata2>; 
 SET <impdata>; 
IF <change from baseline PASI week primary endpoint>/<baseline PASI>=0.90 THEN <PASI 90 response> =1; 
ELSE <PASI 90 response>=0; 
<…repeat for all PASI response…> 
 
IF <baseline IGA> >=3 THEN DO; 
 
     IF <IGA week primary endpoint> < 1.5 THEN <IGA 0/1 response> =1; 
 
ELSE IF <IGA week primary endpoint> >=1.5 THEN <IGA 0/1 response> =0; 
 
ELSE PUT "E" "RROR:" stysid1a=; 
END; 
ELSE IF <baseline IGA>=2 THEN DO; 
 
     IF <IGA week primary endpoint> < 0.5 THEN <IGA 0/1 response> =1; 
 
ELSE IF <IGA week primary endpoint> >=0.5 THEN <IGA 0/1 response> =0; 
 
ELSE PUT "E" "RROR:" stysid1a=; 
END; 
ELSE <IGA 0/1 response> =0; 
RUN; 
 
The treatment differences for each imputed data set will then be evaluated by Logistic 
regression and ODDS ratio as described in Section 5.4.1.1. This analysis will be done by 
_IMPUTATION_ for the comparison between treatment group. The model should be 
estimating response probability = 1 by using DESECENDING option. Using the ESTIMATE 
option in the GENMOD procedure and the ODS OUTPUT data set “Estimates” provides the 
estimate for the odds ratio and confidence intervals. 
 
PROC GENMOD <option>; 
CLASS <stratum> <treatment>; 


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MODEL <response> = <explanatory variables> / link=logit dist=bin type3; 
BY <by-variables); 
ESTIMATE “OR. AIN 300 mg q2wVS. 300mg q4w” <treatment> 1 -1/exp;  
ODS OUTPUT Estimates=Estimates; 
RUN; 
The MIANALYZE procedure expects the parameter estimate in the variables ESTIMATE, and 
the corresponding standard error in the variable STDERR. Measurements can be obtained from 
“Estimates” dataset by selecting the row with ODDS ratio estimates.  
 
Data <modified dataset>; 
  set Estimates; 
  if substr(label,1,3)= “Exp”; 
  ESTIMATE=LBetaEstimate; 
  STDERR=StdErr; 
  effect= “OR”; 
  if missing(ESTIMATE) or missing(STDERR) then delete; 
RUN;  
 
The estimates and standard errors based on the 100 imputed data are then combined by applying 
Rubin’s rules for multiple imputed data sets, see Little and Rubin (2002).  
Programming notes:  
• The variables ESTIMATE and STDERR in the input data set for the MIANALYZE 
procedure may not be missing. Records with missing values need to be deleted and the 
variable _IMPUTATION_ needs to be renumbered and regenerated since for each by-
group the procedure expects consecutive numbers starting at 1. 
• The ESTIMATE and STDERR in terms of odds ratios from logistic regressions will be 
transformed to follow a normal distribution before MIANALYZE procedure. They will 
be transformed back to Odds Ratio to get the corrected ESTIMATE and corresponding 
CIs.   
The SAS procedure MIANALYZE will be applied as follows: 
Step 1: 
DATA <modified dataset_t>; 
 
SET <modified dataset>; 
 
estimate=log(ESTIMATE); 
 
stderr=(log(LBETAUPPERCL)-log(LBETALOWERCL))/(2*1.96); 
RUN ; 
 
ODS LISTING CLOSE; 
ODS OUTPUT ParameterEstimates=<results> VarianceInfo=<varinfo> ModelInfo=<modelinfo>; 
PROC MIANALYZE PARMS=<modified dataset>; 
  BY <by-variables>; 
  MODELEFFECTS estimate; 
  Stderr stderr; 
RUN; 
ODS LISTING; 
 
data <results_back>; 
 
set <results>; 
 
estimate=exp(ESTIMATE); 


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LCLMEAN=estimate*exp(-1.96*stderr); 
 
UCLMEAN=estimate*exp(+1 96*stderr); 
RUN ; 
5.4.2 
Secondary analysis 
5.4.2.1 
Analysis of binary (and categorical) data 
Summary statistics for discrete variables will be presented in contingency tables and will 
include absolute and relative frequencies. If applicable, confidence intervals will be derived as 
well based on the score method including continuity correction [Newcombe (1998)]: 
With z as (1-alpha/2)-quantile of the standard normal distribution (SAS: z=PROBIT(1-alpha/2), 
n  as total number of subjects (i.e. number of subjects in the denominator), and p as estimated 
crude incidence (number of subjects with event / n ) it is 
 
Then the lower limit is for 
 
(
)
(
)










+
+
+
−
−
−
−
+
=
2
2
2
2
1
4
1
2
1
2
,0
max
z
n
nq
p
n
z
z
z
np
L
 
and the upper limit is for 
 
(
)
(
)










+
−
+
−
+
+
+
+
=
2
2
2
2
1
4
1
2
1
2
,1
min
z
n
nq
p
n
z
z
z
np
U
. 
For response variables (e.g. for IGA mod 2011 0 or 1, 
, PASI 90 and 
 
 response) the adjusted response rates (risk difference) including 95% confidence interval 
will be derived by visit. 
For time courses of response variables, the point estimate at each time point including 95% 
confidence interval will be plotted. 
5.4.2.2 
Crude incidence and 100*(1-α)% confidence interval 
For n subjects, each at risk to experience a certain event with probability π, the crude incidence 
is estimated as p=x/n, where x is the number of subjects with the event. 
Absolute and relative frequencies will be displayed as well as 95% confidence interval for the 
relative frequency based on the score method including continuity correction (Newcombe 1998).  
With z  as (1-α/2)-quantile of the standard normal distribution (SAS: z=PROBIT(1-alpha/2), 
n  as total number of subjects (i.e. number of subjects in the denominator), and p as estimated 
crude incidence (number of subjects with event / n ) it is 
. 
Then the lower limit is 
p
q
−
=1
(
),
0
for
0
,0
=
=
>
p
L
p
(
),
1
for
1
,1
=
=
<
p
U
p
p
q
−
=1


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(
)
(
)










+
+
+
−
−
−
−
+
=
2
2
2
2
1
4
1
2
1
2
,0
max
z
n
nq
p
n
z
z
z
np
L
 
and the upper limit is 
(
)
(
)










+
−
+
−
+
+
+
+
=
2
2
2
2
1
4
1
2
1
2
,1
min
z
n
nq
p
n
z
z
z
np
U
. 
Note: if p = 0 then L = 0 and if p = 1 then U = 1. 
If appropriate, an exact 100*(1-α)% confidence interval (Clopper-Pearson 1934) will be 
obtained by using the SAS procedure PROC FREQ with the EXACT BINOMIAL statement. 
However, the confidence interval derived via the score method including continuity correction 
will be the default in safety analyses. 
5.4.2.3 
Risk difference and 100*(1-α)% confidence interval 
For an investigational drug group with n1 subjects at risk, independent from the control group 
(e.g., placebo or comparator) with n0 subjects at risk, of whom x1 and x0 experience a certain 
event, the risk difference is estimated as p1-p0 with p1= x1/n1 and p0=x0/n0.  
Exact unconditional confidence limits for the risk difference will be obtained with SAS 
procedure PROC FREQ and option RISKDIFF in the TABLES statement, specifying the 
RISKDIFF option also in the EXACT statement.  
5.5 
Rule of exclusion criteria of analysis sets  
Protocol deviations for exclusion from analysis sets are defined in Table 5-1.  
Table 5-1 
Subject classification rules 
Analysis set 
PD Categories Codes that 
cause subject to be excluded 
Non-PD criteria that cause a 
subject to be excluded 
Randomization set 
DVSPID: INCL01a;  
Misrandomized subject 
FAS (Full Analysis Set)  
DVSPID: INCL01a; OTH14 
Misrandomized subject 
Safety 
DVSPID: INCL01a; OTH14 
Subjects who did not take any 
study treatment 
INCL01a: ICF missing or not signed 
OTH14: Severe ICH-GCP non-compliance of study site 
 
 


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6 
Reference 
Bretz F, Maurer W, Brannath W, Posch M (2009) A graphical approach to sequentially rejective 
multiple test procedures. Statistics in Medicine; 28: 586-604. 
Clopper CJ, Pearson ES (1934). The use of confidence or fiducial limits illustrated in the case 
of the binomial. Biometrika, 26; 404–413. 
Committee for medicinal products for human use (CHMP), European Medicines Agency for 
the Evaluation of Medicines for Human Use. (2004) Guideline on clinical investigation of 
medicinal products indicated for the treatment of psoriasis. CHMP/EWP/2454/02 corr 
document. London, UK. 
Fredriksson T, Pettersson U (1978) Severe psoriasis—oral therapy with a new retinoid. 
Dermatologica; 157:238–44. 
Gottlieb A, Griffiths CEM, Ho VC, et al (2005) Efficacy and tolerability of oral pimecrolimus 
in the treatment of moderate to severe chronic plaque type psoriasis: a double-blind, 
multicentre, randomized dose-finding trial. Br J Dermatol; 152:1219-27. 
Lachin JM (2000) The assessment of relative risks . New York: Wiley 
Little, R.J.A and Rubin, D.B. (2002). Statistical Analysis with Missing Data. Wiley Series in 
Probabiliy and Statistics, Chapter 10. 
Menter A, Gottlieb A, Feldman S, et al (2008) Guidelines of care for the management of 
psoriasis and psoriatic arthritis – Section 1. Overview of psoriasis and guidelines of care for the 
treatment of psoriasis with biologics. J Am Acad Dermatol; 58:826-850. 
Newcombe RG (1998) Two-sided confidence intervals for the single proportion: comparison 
of seven methods. Statistics in Medicine; 17: 857-872. 
Program Case Retrieval Sheet available in GPS at the path 
. 
Rubin, D.B. (1987). Multiple Imputation for Nonresponse in Surveys. New York: Wiley. 
Schaefer, J.L. (1997). Analysis of Incomplete Multivariate Data, Chapman&Hall. 
Weisman S, Pollack CR, Gottschalk RW (2003) Psoriasis disease severity measures: 
comparing efficacy of treatments for severe psoriasis. J Dermatolog Treat; 14: 158-165.