Conditions: Scalp Psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 231
Healthy volunteers: no

Brief summary:
This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of tildrakizumab in the treatment of moderate to severe psoriasis of the scalp.

Detailed description:

Arms:
arm 1: None arm 2: None arm 3: The subjects will not receive study treatment during the follow-up period

Interventions: intervention 1: PART 1: Double-blind Placebo-controlled intervention 2: PART 2: Double-blind Active Treatment Extension
Intervention descriptions: intervention 1: all eligible subjects will receive either tildrakizumab or placebo intervention 2: subjects initially on placebo will be switched over to receive tildrakizumab while subjects initially on tildrakizumab will continue to receive tildrakizumab as per defined schedule

Protocol document:
Prot_000.pdf: 
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled clinical study 
to assess the efficacy and safety of Tildrakizumab in the treatment of moderate to severe 
plaque psoriasis of the scalp 
 
Document: Clinical Study Protocol 
 
NCT number: NCT03897088 
 
Date: 17-Mar-2020 


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TITLE PAGE 
Protocol Title:  
A Multicenter, Randomized, Double-Blind, Placebo-Controlled 
Clinical Study to Assess the Efficacy and Safety of Tildrakizumab in 
the Treatment of Moderate to Severe Plaque Psoriasis of the Scalp 
Protocol Number:  
 
TILD-18-20 
  
 
  
 
Product:  
 
 
Tildrakizumab 
Short Title:  
Efficacy and Safety Profile of Tildrakizumab in Subjects with 
Moderate to Severe Plaque Psoriasis of the Scalp. 
Study Phase:   
 
3b 
Sponsor Name:  
 
Sun Pharma Global FZE 
Legal Registered Address:  
Office # 43, Block Y,  
SAIF Zone 
Sharjah, 122304 
United Arab Emirates 
Regulatory Agency Identifying Number: IND number 101,389 
  
 
 
 




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TABLE OF CONTENTS 
SUMMARY OF CHANGES .........................................................................................................3 
LIST OF APPENDICES .............................................................................................................11 
LIST OF TABLES .......................................................................................................................12 
LIST OF FIGURES .....................................................................................................................12 
1.0 
PROTOCOL SUMMARY ..............................................................................................13 
1.1 
Synopsis .................................................................................................................13 
 
 
 
 
2.0 
INTRODUCTION............................................................................................................25 
2.1 
Background ............................................................................................................25 
2.2 
Study Rationale ......................................................................................................25 
2.3 
Benefit/Risk Assessment .......................................................................................26 
3.0 
OBJECTIVES AND ENDPOINTS ................................................................................27 
4.0 
STUDY DESIGN ..............................................................................................................30 
4.1 
Overall Design .......................................................................................................30 
4.2 
Scientific Rationale for Study Design....................................................................31 
4.3 
Justification for Dose .............................................................................................31 
4.4 
End of Study Definition .........................................................................................32 
5.0 
STUDY POPULATION ..................................................................................................33 
5.1 
Inclusion Criteria ...................................................................................................33 
5.2 
Exclusion Criteria ..................................................................................................34 
5.3 
Lifestyle Considerations ........................................................................................35 
5.4 
Screen Failures .......................................................................................................36 
6.0 
STUDY TREATMENT ...................................................................................................37 
 
 
6.2 
Preparation/Handling/Storage/Accountability .......................................................38 
6.3 
Measures to Minimize Bias: Randomization and Blinding ...................................38 
6.4 
Study Treatment Compliance ................................................................................39 
6.5 
Concomitant Therapy.............................................................................................39 
6.5.1 
Rescue Medicine ...................................................................................40 
 
 
6.6 
Dose Modification .................................................................................................40 
6.7 
Treatment after the End of the Study .....................................................................40 


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7.0 
DISCONTINUATION OF STUDY TREATMENT AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ......................................................................41 
7.1 
Discontinuation of Study Treatment ......................................................................41 
7.1.1 
Temporary Discontinuation ..................................................................41 
7.2 
Subject Discontinuation/Withdrawal from the Study ............................................42 
7.3 
Lost to Follow-up ...................................................................................................42 
8.0 
STUDY ASSESSMENTS AND PROCEDURES ..........................................................44 
8.1 
Efficacy Assessments.............................................................................................44 
8.1.1 
Assessments for Scalp: ..........................................................................45 
8.1.2 
Assessments for Whole Body: ..............................................................45 
8.1.3 
Dermatology Life Quality Index ...........................................................46 
8.2 
Safety Assessments ................................................................................................46 
8.2.1 
Physical Examinations ..........................................................................47 
8.2.2 
Vital Signs .............................................................................................47 
8.2.3 
Assessment of Suicidal Ideation and Behavior .....................................47 
8.2.4 
Electrocardiograms ...............................................................................48 
8.2.5 
Tuberculosis Testing .............................................................................48 
8.2.6 
Chest X-ray ...........................................................................................48 
8.2.7 
Clinical Safety Laboratory Assessments ...............................................48 
8.3 
Adverse Events ......................................................................................................49 
8.3.1 
Time Period and Frequency for Collecting AE and SAE 
Information ............................................................................................49 
8.3.2 
Method of Detecting AEs and SAEs .....................................................50 
8.3.3 
Follow-up of AEs and SAEs .................................................................50 
8.3.4 
Regulatory Reporting Requirements for SAEs .....................................50 
8.3.5 
Pregnancy ..............................................................................................51 
8.3.6 
Adverse Events of Special Interest .......................................................52 
8.3.7 
Events of Clinical Interest .....................................................................52 
8.4 
Treatment of Overdose ..........................................................................................52 
8.5 
Pharmacokinetics ...................................................................................................53 
8.6 
Pharmacodynamics ................................................................................................53 
8.7 
Genetics..................................................................................................................53 
8.8 
Biomarkers .............................................................................................................53 
8.9 
Health Economics or Medical Resource Utilization and Health Economics ........53 
9.0 
STATISTICAL CONSIDERATIONS ...........................................................................54 
9.1 
Statistical Hypotheses ............................................................................................54 
9.2 
Sample Size Determination....................................................................................54 


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9.3 
Populations for Analyses .......................................................................................55 
9.4 
Statistical Analyses ................................................................................................56 
9.4.1 
Efficacy Analyses..................................................................................57 
9.4.2 
Safety Analyses .....................................................................................59 
9.4.3 
Other Analyses ......................................................................................61 
 
 
9.5 
Interim Analyses ....................................................................................................61 
9.6 
Monitoring Committee...........................................................................................61 
 
 
 
 
 
LIST OF APPENDICES 
 
Appendix 2: ................. Regulatory, Ethical and study oversight considerations ............................66 
 
Appendix 4: ................. Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting .......................................................77 
Appendix 5: ................. Anaphylaxis ...............................................................................................83 
Appendix 6: ................. Excluded Medications/Therapy .................................................................84 
Appendix 7: ................. Contraceptive guidance and collection of pregnancy ................................85 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 19: ............... Columbia-Suicide Severity Rating Scale .................................................100 
 
 
 


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LIST OF TABLES 
Table 1 ......................... Study Objectives and Endpoints ................................................................27 
Table 2 ......................... Study Treatment Details ............................................................................37 
Table 3 ......................... Analysis Sets ..............................................................................................56 
Table 4 ......................... Efficacy Analyses ......................................................................................57 
Table 5 ......................... Study Administrative Structure..................................................................68 
Table 6 ......................... Protocol-required Safety Laboratory Assessments ....................................74 
Table 7 ......................... Excluded Medications ................................................................................84 
 
LIST OF FIGURES 
Figure 1: ....................... Study Schema.............................................................................................21 
 
 
 
 
 
 
 






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Objectives 
Endpoints 
• 
To assess the efficacy of tildrakizumab in 
subjects with moderate to severe plaque 
psoriasis of the scalp, as measured by the 
proportion of subjects who achieve at least 
90% improvement from Baseline in the 
Psoriasis Scalp Severity Index (PSSI) 
response at Week 16 compared with placebo. 
• 
To assess the efficacy of tildrakizumab in 
subjects with moderate to severe scalp 
psoriasis, as measured by the proportion of 
subjects who achieve IGA (Scalp only) of 
“clear” and “almost clear” with at least 
2-point reduction from Baseline at Week 16. 
• 
To assess the efficacy of tildrakizumab in 
subjects with moderate to severe scalp 
psoriasis, as measured by the proportion of 
subjects who achieve Investigator Global 
Assessment (IGA) mod 2011 (scalp) score of 
“clear” and “almost clear” with at least 
2-point reduction from Baseline at Week 12. 
• 
To assess the efficacy of tildrakizumab in 
subjects with moderate to severe plaque 
psoriasis of the scalp, as measured by the 
proportion of subjects who achieve at least 
90% improvement from Baseline in the 
Psoriasis Scalp Severity Index (PSSI) 
response at Week 12 compared with placebo. 
To assess the efficacy of tildrakizumab in the 
treatment of moderate to severe plaque 
psoriasis of the scalp compared with placebo 
as measured by scalp surface area 
involvement at Week 16. 
• 
The proportion of subjects with at 
least 90% improvement from 
Baseline in the PSSI at Week 16. 
(Key secondary endpoint). 
• 
The proportion of subjects with IGA 
(scalp only) score of “clear” and 
“almost clear” with at least 2-point 
reduction from Baseline at Week 16. 
(Key secondary endpoint). 
• 
The proportion of subjects with IGA 
mod 2011 (scalp) score of “clear” and 
“almost clear” with at least 2-point 
reduction from Baseline at Week 12 
(key secondary endpoint) 
• 
The proportion of subjects with at 
least 90% improvement from 
Baseline in the PSSI at Week 12. 
(Key secondary endpoint). 
• 
Mean percentage change in PSSI 
score from Baseline to Week 16. 
• 
The proportion of subjects achieving 
PSSI 75 at Week 16. 
• 
The proportion of subjects achieving 
PSSI 100 at Week 16. 
• 
Mean percentage change in scalp 
surface area involvement from 
Baseline to Week 16. 
• 
To assess the effect of Tildrakizumab on IGA 
mod 2011 (scalp) and PSSI at other measured 
time points through week 52. 
• 
To assess the effect of tildrakizumab on, IGA 
(scalp only), Scalp Itch NRS, PASI, PGA-S 
(whole body), IGA mod 2011 (whole body) at 
week 12 and other measured time points 
through Week 52.  
• 
Change from baseline in IGA mod 2011 
(scalp) and PSSI at other measured time 
points through Week 52. 
• 
Change from Baseline in IGA (scalp only), 
Scalp Itch NRS, PASI, PGA-S (whole body), 
and IGA mod 2011 (whole body) at week 12 
and other measured time points through Week 
52. 




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After a Screening Period of 28 days, all eligible subjects will be randomly allocated 
 
 
 on Day 1 to receive either tildrakizumab 100 mg or placebo by subcutaneous (SC) injection 
 
 
 
 subjects initially randomized to placebo will be switched over to receive tildrakizumab 100 mg 
 and subjects initially randomized to tildrakizumab 100 mg will continue to 
receive tildrakizumab 
In order to maintain the blind, subjects in both treatment 
arms will receive matching placebo injections at specified time points as described in the Schedule of 
Activities (SoA). 
After Week 52 (or early termination of study treatment prior to Week 52), the study treatment should be 
stopped, and the subjects will enter the 
Observational Safety Follow-up Period following the last 
dose of study treatment. During the follow-up period, subjects should continue on study-approved 
concomitant medications only, however may be placed on other appropriate therapies for safety concerns 
or significant worsening of psoriasis based on the judgment of the Investigator. The subjects will not receive 
study treatment during the follow-up period. 
The subject’s disease activity (response to study treatment) will be evaluated using the IGA Mod 2011 
(scalp), PSSI, PASI, IGA (scalp only), PGA-S (whole body), IGA Mod 2011 (whole body), Scalp Itch 
Numeric Rating Scale (NRS), BSA, and Dermatology Life Quality Index (DLQI) scores.  
Safety assessments including adverse event (AE)/serious adverse event (SAE) monitoring, vital signs, 
physical examinations, electrocardiogram, and laboratory measurements will be performed during the 
study.  
 
 
Number of Investigators and Study Centers: 
Up to 
 Investigators and study centers (in United States and Australia) are expected to participate in this 
study. 
Number of Subjects: 
The study will randomize approximately 107 subjects per treatment arm (Total N=214) 
 
randomization to either tildrakizumab 100 mg arm or placebo arm.  
Treatment Groups 
 
 
 
The study consists of a Screening Period 
 treatment period (
double-blind 
placebo-controlled treatment period followed by 
 double-blind active treatment period), and  
 Observational Safety Follow-up Period. 
Part 1: Double-blind placebo-controlled, where subjects will receive either tildrakizumab 
 (Arm A) 
or placebo (Arm B) 
 


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Protocol TILD-18-20- 
  
 
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Part 2: At Week 16, subjects initially randomized to placebo will be switched over to receive tildrakizumab 
100 mg 
 Subjects initially randomized to tildrakizumab 100 mg will continue 
to receive active drug 
 In order to maintain the blind, subjects in both treatment 
arms will receive matching placebo injections at specified time points as described in the SoA.  
Part 3: After Week 52 (or early termination of study treatment prior to Week 52), subjects will enter the 
Observational Safety Follow-up Period where tildrakizumab treatment will be stopped. 
Statistical methods: 
The primary efficacy endpoint for this study is the proportion of subjects with IGA mod 2011(scalp) score 
of “clear” and “almost clear” with at least 2-point reduction from baseline at Week 16. The key secondary 
efficacy endpoints are the proportion of subjects with at least 90% improvement in the PSSI (PSSI90) from 
baseline at Week 16, the proportion of subjects with IGA (scalp only) score of “clear” and “almost clear” 
with at least 2-point reduction from baseline at Week 16, the proportion of subjects with IGA mod 
2011(scalp) score of “clear” and “almost clear” with at least 2-point reduction from baseline at Week 12 
and the proportion of subjects with at least 90% improvement in the PSSI (PSSI90) from baseline at 
Week 12. For each endpoint, the tildrakizumab 100 mg dose will be compared with placebo Both the 
primary and key secondary efficacy endpoints will be analyzed with Cochran-Mantel-Haenszel test 
 
using the Intent-to-treat (ITT) population. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Secondary efficacy and exploratory endpoints that are dichotomous will be analyzed 
in the same manner as the primary efficacy endpoint using the ITT population. Continuous secondary 
efficacy and exploratory endpoints will be analyzed using an MMRM procedure 
 
 
 
 
 




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Objectives 
Endpoints 
• 
To assess the efficacy of tildrakizumab in subjects 
with moderate to severe scalp psoriasis, as 
measured by the proportion of subjects who 
achieve IGA (scalp only) score of “clear” and 
“almost clear” with at least 2-point reduction from 
Baseline at Week 16. 
• 
To assess the efficacy of tildrakizumab in subjects 
with moderate to severe scalp psoriasis, as 
measured by the proportion of subjects who 
achieve Investigator Global Assessment (IGA) 
mod 2011 (scalp) score of “clear” and “almost 
clear” with at least 2-point reduction from Baseline 
at Week 12. 
• 
To assess the efficacy of tildrakizumab in subjects 
with moderate to severe plaque psoriasis of the 
scalp, as measured by the proportion of subjects 
who achieve at least 90% improvement from 
Baseline in the Psoriasis Scalp Severity Index 
(PSSI) response at Week 12 compared with 
placebo.To assess the efficacy of tildrakizumab in 
the treatment of moderate to severe plaque 
psoriasis of the scalp compared with placebo as 
measured by scalp surface area involvement at 
Week 16. 
• 
The proportion of subjects with IGA mod 2011 
(scalp) score of “clear” and “almost clear” with at 
least 2-point reduction from Baseline at Week 12 
(key secondary endpoint) 
• 
The proportion of subjects with at least 90% 
improvement from Baseline in the PSSI at 
Week 12. (Key secondary endpoint). 
• 
Mean percentage change in PSSI score from 
Baseline to Week 16. 
• 
The proportion of subjects achieving PSSI 75 at 
Week 16. 
• 
The proportion of subjects achieving PSSI 100 at 
Week 16. 
• 
Mean percentage change in scalp surface area 
involvement from Baseline to Week 16. 
• 
To assess the effect of Tildrakizumab on IGA mod 
2011 (scalp) and PSSI at other measured time 
points through week 52. 
• 
To assess the effect of tildrakizumab on IGA 
(scalp only), Scalp Itch NRS, PASI, PGA-S (whole 
body), and IGA mod 2011 (whole body), at week 
12 and other measured time points through Week 
52. 
• 
Change from baseline in IGA mod 2011 (scalp) 
and PSSI at other measured time points through 
Week 52. 
• 
Change from Baseline in IGA (scalp only), Scalp 
Itch NRS, PASI, PGA-S (whole body) and IGA 
mod 2011 (whole body), at week 12 and other 
measured time points through Week 52. 
• 
To assess the time to response. 
• 
Time to 75% reduction in PSSI during the 
16-week placebo-controlled treatment period. 
• 
Time to IGA mod 2011 (scalp) response during 
the 16-week placebo-controlled treatment period. 
• 
To assess the efficacy of tildrakizumab in the 
improvement of scalp itch as measured by the 
proportion of subjects achieving a 4-point 
reduction in Scalp Itch Numeric Rating Scale 
(NRS) score from Baseline at Week 16 compared 
with placebo. 
• 
Proportion of subjects achieving a 4-point 
reduction in Scalp Itch NRS score from Baseline 
to Week 16. 
• 
To assess the efficacy of tildrakizumab in the 
treatment of moderate to severe psoriasis 
• 
The proportion of subjects achieving PASI 75, 




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4.0 
STUDY DESIGN 
4.1 
Overall Design 
This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy 
and safety of tildrakizumab in the treatment of moderate to severe psoriasis of the scalp. The study 
will be conducted in up to 35 study centers across the United States and Australi
 
 
 
 
Approximately 214 subjects (approximately 107 per arm) with moderate to severe psoriasis of the 
scalp will be enrolled in the study. Eligible subjects will be randomized to 1 of the 2 arms 
 
 Arm A: Tildrakizumab 100 mg, SC (n=107) and Arm B: Placebo, SC (n=107). 
 
 
 
 
 
The study will comprise of 3 parts: 
PART 1: Double-blind Placebo-controlled (Day 1 to Week 16) 
After a Screening Period of up to 28 days and on Day 1, all eligible subjects will be randomized 
 to receive either tildrakizumab 100 mg or placebo 
 
 Subjects should receive the first dose of study treatment within 24 hours of 
randomization.
 
 
PART 2: Double-blind Active Treatment Extension (Week 16 to Week 52) 
subjects initially randomized to placebo will be switched over to receive 
tildrakizumab 
while subjects initially randomized to 
tildrakizumab 100 mg will continue to receive tildrakizumab 
 In order 
to maintain the blind, subjects in both treatment arms will receive matching placebo injections at 
specified time points as described in the Schedule of Activities (SoA) 
 
PART 3: Observational Safety Follow-up (Week 52 to Week 72) 
After Week 52 (or early termination of study treatment prior to Week 52), the study treatment 
should be stopped and all subjects, including those who terminated early from Part 1 and 2 will 
enter the 
Observational Safety Follow-up Period to monitor safety and tolerability 
 
 following last dose of study treatment. During the follow-up period, subjects should 
continue on study-approved concomitant medications only, however may be placed on appropriate 






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5.0 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Subjects are eligible to be included in the study only if all of the following criteria apply: 
1. Subjects should be 18 years or older at the time of signing the informed consent during the 
Screening visit. 
2. Subjects with a clinical diagnosis of chronic plaque psoriasis of at least 6 months (as determined 
by-subject interview and confirmation of diagnosis through physical examination by 
Investigator). 
3. Subjects must have moderate to severe plaque psoriasis of the scalp at Screening and at 
Baseline, defined by: 
• 
Scalp Investigator Global Assessment (IGA mod 2011 (scalp) of ≥3 
• 
Psoriasis Scalp Severity Index (PSSI) score of ≥12 
• 
≥30% or scalp surface area affected. 
4.  Subject must have moderate to severe plaque psoriasis at Screening and Baseline defined by  
• IGA mod 2011 (whole body) of at least moderate severity (score of ≥3 on a 5-pointer 
scale) 
• PASI score of ≥12 
• Body Surface Area (BSA) involvement of >10%  
5. Subjects must be considered candidates for systemic therapy, meaning scalp psoriasis 
inadequately controlled by topical treatments (corticosteroids), and/or phototherapy, and/or 
previous systemic therapy. 
6. Subjects has a negative evaluation for tuberculosis (TB) within 4 weeks before initiating study 
treatment, defined as a negative QuantiFERON® test. Subjects with a positive or 2 successive 
indeterminate. QuantiFERON® tests are allowed if they have all of the following: 
• No history of active TB or symptoms of TB. 
• A posterior-anterior chest radiogram (with associated report available at study center) 
performed within 3 months of Screening with no evidence of active TB (or of any other 
pulmonary infectious diseases). 
• If prior latent TB infection (LTBI), must have history of adequate prophylaxis (per local 
standard of care). 
• If presence of LTBI is established, then treatment according to local country guidelines 
must have been followed for 4 weeks prior to inclusion in the study. 
A maximum of 2 QuantiFERON® tests are allowed. A re-test is only permitted if the first is 
indeterminate; the result of the second test will then be used. 


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7. Subjects are unlikely to conceive, as indicated by at least one “Yes” answer to the following 
questions: 
• 
Subject is a male. 
• 
Subject is a female and agrees to abstain from heterosexual activity OR use a highly 
effective method of contraception as per Appendix 7.  
• 
Male subjects with female partners of childbearing potential who are not using birth 
control as described above must use a barrier method of contraception (eg, condom) if 
not surgically sterile (ie, vasectomy). 
• 
Subject is a surgically sterilized female or is documented to be postmenopausal.  
For contraceptive guidance see Appendix 7 
8. For women of childbearing potential, a negative serum pregnancy test at Screening and a 
negative urine pregnancy test within 24 hours prior to Day 1 and on subsequent visits at which 
study treatment doses are scheduled. 
9. Subjects must have results of a physical examination within normal limits or clinically 
acceptable limits to the Investigator prior to Day 1. The Investigator is encouraged to consult 
with the Medical Monitor (or appropriate designee) if there are questions regarding the 
significance of any out-of-range values. 
10. Subjects must be capable of giving signed informed consent as described in Appendix 2, which 
includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 
5.2 
Exclusion Criteria  
Subjects are excluded from the study if any of the following criteria apply: 
1. Subjects who have laboratory abnormalities at Screening including any of the following: 
• 
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.5 × the upper 
limit of normal (ULN) 
• 
Creatinine ≥2 × the ULN 
• 
Serum direct bilirubin ≥1.5 mg/dL 
• 
White blood cell count <3.0×103/μL 
• 
Any other laboratory abnormality, which, in the opinion of the Investigator, will prevent 
the subject from completing the study or will interfere with the interpretation of the 
study results. 
2. Subjects who have predominantly non-plaque forms of psoriasis specifically erythrodermic 
psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated 
psoriasis, or new-onset guttate psoriasis. 
3. Women of childbearing potential who are pregnant, intend to become pregnant (within 
6 months of completing the study), or are lactating. 
4. Subjects with any infection or history of recurrent infection requiring treatment with systemic 
antibiotics within 2 weeks prior to Screening, or severe infection (eg, pneumonia, cellulitis, 
bone or joint infections) requiring hospitalization or treatment with intravenous (IV) antibiotics 
within 6 weeks prior to Screening. 


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5. Subjects with any previous use of tildrakizumab or other IL-23/Th-17 pathway inhibitors, 
including p40, p19 and IL-17 antagonists for psoriasis. 
• 
Prior use of TNF-alpha inhibitors with a wash-out period of 12 weeks would be allowed. 
However, the number of subjects with prior use of TNF-alpha inhibitors would be 
capped at 40% and the analysis will be stratified based on prior use of these biologics. 
6. Subjects with a positive human immunodeficiency virus test result, hepatitis B surface antigen, 
or hepatitis C virus test result. 
7. Subjects with a prior malignancy or concurrent malignancy (excluding successfully treated 
basal cell carcinoma, squamous cell carcinoma of the skin in situ, squamous cell carcinoma of 
skin with no evidence of recurrence within 5 years or carcinoma in situ of the cervix that has 
been adequately treated). 
8. Subjects who have received live viral or bacterial vaccination within 4-weeks prior to Baseline 
or who intend to receive live viral or bacterial vaccination during the study. 
9. Subjects who are currently participating in another interventional clinical study or has 
participated in an interventional clinical study within 5-half-lives (of the drug) to wash-out prior 
to randomization (Subjects participating in observational studies or non-interventional registry 
studies may be included in the study). 
10. Subjects or a family member is among the personnel of the study center or Sponsor/designee 
staff directly involved with this study. 
11. Subjects who have any concomitant medical condition which in the opinion of the Investigator 
could affect the study outcome or present an unacceptable risk. 
12. Subjects who were hospitalized due to an acute cardiovascular event (such as myocardial 
infarction, cerebrovascular accident, 
cardiovascular illness [eg, angina pectoris], or 
cardiovascular surgery [such as coronary artery bypass grafting (CABG)]) within 6 months 
before Screening. 
13. Subjects who, in the opinion of the Investigator, will not be a reliable participant in the study 
and those who can confound the results of the study. 
14. Subjects who have a history of alcohol or drug abuse in the previous year. 
15. Subjects who have high risk of suicidality at the Screening assessment based on Investigator’s 
judgment or, if appropriate, as indicated by a response of “yes” within the last 12 months to 
Questions 4 or 5 in the suicidal ideation section, or any positive response in the behavioral 
section of the C-SSRS.  
16. Subjects with any other clinically significant laboratory abnormality, which, in the opinion of 
the Investigator, will prevent the subject from completing the study or will interfere with the 
interpretation of the study results. 
5.3 
Lifestyle Considerations 
Excessive exposure to sunlight should be avoided during the study. Subjects should avoid use of 
tanning booths or other ultraviolet light sources for the duration of the study. 


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5.4 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently entered in the study. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure subjects to meet the Consolidated Standards of Reporting 
Trials publishing requirements and to respond to queries from regulatory authorities. The minimal 
information includes demography, screen failure details, eligibility criteria, and any SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened at the discretion of the Investigator for up to 2 additional times, with a minimum of 
2 weeks between each rescreening. When a subject is rescreened, all Screening procedures will be 
repeated.   
Note:  If the original ICF was signed within 30 days of the rescreening visit, a new ICF does not 
need to be completed. 
Rescreened subjects should not be assigned the same subject number as for the initial Screening. 
Any subject who is started on prophylactic treatment for latent TB during the Screening Period 
may be randomized 4 weeks after initiation of treatment without need for rescreening. 
 
 


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6.0 
STUDY TREATMENT 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a subject according to the study protocol. 
The study treatment in this study is tildrakizumab and placebo. 
 
The study arms will receive study 
treatment during the course of the study as follows: 
Arm A: 
o
Tildrakizumab 100 mg SC injections 
o
Placebo injections 
Arm B: 
o
Placebo injections 
o
Tildrakizumab 100 mg SC injections
 
 
 
 
 
Study Treatment Name: 
Tildrakizumab 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
Unit Dose Strength/Dosage 
Level: 
100 mg 
- 
Route of Administration 
Subcutaneous (SC) 
SC 
 
 
 
 
 
  
 
 
 


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Protocol TILD-18-20- 
 
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6.2 
Preparation/Handling/Storage/Accountability 
1. The Investigator or designee must confirm appropriate temperature conditions have been
maintained during transit for all study treatment received and any discrepancies are reported
and resolved before use of the study treatment.
2. Only subjects enrolled in the study may receive study treatment and only authorized study
center staff may supply or administer the study treatment. All study treatments must be stored
in a secure, environmentally controlled, and monitored (manual or automated) area in
accordance with the labeled storage conditions with access limited to the Investigator and
authorized study center staff.
3.
Study treatment experiencing temperature excursions outside this temperature should
be quarantined and can only be released for subject use after consultation with the Sponsor.
4. The Investigator, institution, or the head of the medical institution (where applicable) is
responsible for study treatment accountability, reconciliation, and record maintenance (ie,
receipt, reconciliation, and final disposition records).
5. Further guidance and information for the final disposition of unused study treatment will be
provided by the study center monitor.
The Investigator, a member of the study center staff, or a hospital pharmacist must maintain an 
adequate record of the receipt and distribution of all study treatment using the Drug Accountability 
Form.  
6.3 
Measures to Minimize Bias: Randomization and Blinding 
All subjects will be centrally assigned 
 to receive either tildrakizumab 100 mg or 
placebo using an Interactive Web Response System (IWRS). Before the study is initiated, the log 
in information and directions for the IWRS will be provided to each study center. 
This is a double-blind study with limited access to the randomization code. Tildrakizumab and 
placebo will be identical in physical appearance.
 
 
 
 
Study treatment will be dispensed at the study visits summarized in the SoA 
 
 
Returned study treatment should not be re-dispensed to the subjects. 


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39 
 In case of an emergency, the 
Investigator has the sole responsibility for determining if unblinding of a subject’s treatment 
assignment is warranted. Subject safety must always be the first consideration in making such a 
determination. If the Investigator decides that unblinding is warranted, the Investigator should 
make every effort to contact the Sponsor prior to unblinding a subject’s treatment assignment 
unless this could delay emergency treatment of the subject. If a subject’s treatment assignment is 
unblinded, the Sponsor must be notified within 24 hours after breaking the blind. The date and 
reason that the blind was broken must be recorded in the source documentation and electronic case 
report form (eCRF), as applicable. 
A designated member of the Sponsor’s safety team will be unblinded for any Suspected 
Unexpected Serious Adverse Reactions, for regulatory reporting purposes. Unblinding is for 
regulatory reporting purpose only 
 
 
6.4 
Study Treatment Compliance 
The prescribed dosage, timing, and mode of administration may not be changed. Any departures 
from the intended regimen must be recorded in the eCRFs. 
 
Study treatment accountability and subject compliance will be documented throughout the 
treatment periods 
 using study-specific study treatment dispensing record forms. 
If a subject does not receive the scheduled dose, every effort should be made to administer the 
dose as soon as possible. 
6.5 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, and/or 
herbal supplements) that the subject is receiving at the time of enrollment or receives during the 
study must be recorded on the eCRF along with: 
• 
Reason for use. 
• 
Dates of administration including start and end dates. 
• 
Dosage information including dose and frequency. 
In addition, all prior medications used to treat the disease conditions and any other medications 
taken within 6 months prior to enrollment must be recorded in the eCRF.  
The Medical Monitor should be contacted if there are any questions regarding concomitant or prior 
therapy. 


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Other concomitant medication may be considered on a case-by-case basis by the Investigator in 
consultation with the Medical Monitor if required. 
6.5.1 
Rescue Medicine 
Not applicable. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.6 
Dose Modification 
No dose modification is allowed in this study. Study treatment can be interrupted temporarily or 
permanently if deemed necessary as per the Investigator’s discretion. 
6.7 
Treatment after the End of the Study 
The Sponsor will not provide any study treatment to the subjects during the Observational Safety 
Follow-up Period. Patient care should not differ from what is normally expected for subjects with 
psoriasis.  
 
 


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7.0 
DISCONTINUATION 
OF 
STUDY 
TREATMENT 
AND 
SUBJECT 
DISCONTINUATION/WITHDRAWAL  
7.1 
Discontinuation of Study Treatment  
Subjects may voluntarily discontinue study treatment for any reason at any time and enter the 
wash-out period, or completely withdraw from the study
 Subjects who 
consent to enter the wash-out period will undergo the Week 52 (EoT) assessment a minimum of 
4-weeks after administration of the last dose of study treatment.  
At any time during Part 1 or Part 2 of the study, the Investigator should discontinue study treatment 
of a given subject if, on balance, he/she believes that continuation would be detrimental to the 
subject’s well-being.  
The study treatment must be discontinued under the following circumstances and the further steps 
need to be discussed with the Medical Monitor: 
• An SAE, drug reaction or complication, or an unacceptable AE, whether attributed to study 
treatment or not, that precludes continuation of treatment with study treatment. This 
includes the development of allergic reactions or the development of other potentially 
serious drug reactions to medication required by the protocol 
• Diagnosis of malignancy (except basal or squamous cell carcinoma of skin) during study 
(at discretion of the subject and Investigator) 
• Subjects who develop suicidal behavior 
• Evidence of pregnancy 
• Withdrawal of informed consent 
• Lost to follow-up 
• Significant non-compliance of the subject with study procedures 
• Decision of the Sponsor to terminate the subject, study center, or the study. 
 
Subjects who withdraw from the study at any part will undergo the Week 52 (EoT) assessments. 
Patient related outcome (PRO) measurement should be obtained immediately after subject 
withdrawal.  Week 52 (EoT) assessments should be conducted a minimum of 4-weeks after 
administration of the last dose of study treatment. 
See the SoA 
 for data to be collected at the time of treatment discontinuation and 
follow-up and for any further evaluations that need to be completed. 
7.1.1 
Temporary Discontinuation  
Study treatment can be interrupted temporarily in case of:  


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• Clinically important laboratory abnormalities. 
• Subjects who develop suicidal ideation. 
• Other intercurrent illnesses or major surgery. 
• Use of prohibited treatment. 
• Any other protocol deviation that results in a significant risk to the subject’s safety. 
• Sponsor decision. 
The Medical Monitor should be informed. Re-starting of study treatment at the next scheduled 
administration study visits can be done after discussion with the Medical Monitor. 
7.2 
Subject Discontinuation/Withdrawal from the Study 
Subjects may voluntarily withdraw consent to participate in the study for any reason at any time. 
Withdrawal of consent occurs when a subject does not want to participate in the study anymore 
and does not want to attend any further visits or assessments, have further study-related contact, 
or allow analysis of already obtained biologic material. 
If a subject withdraws consent, the Investigator must make every effort to determine the primary 
reason for this decision and record this information on the treatment disposition eCRF page. If the 
subject decides to completely withdraw from the study (refuses any further study participation or 
contact), all study participation for that subject will cease and data to be collected at subsequent 
visits will be considered missing. The study treatment must be discontinued, and no further 
assessments conducted. Further attempts to contact the subject are not allowed unless safety 
findings require communication or follow-up. 
However, for safety reasons, Week 52 (EoT) assessments should be conducted for subjects 
withdrawing during Part 1 or 2, if the withdrawn subject is willing to undergo the assessments. For 
subjects withdrawing during Part 3 and willing to undergo final assessments, the Week 72 (EoS) 
assessments should be conducted at least 4 weeks after their last visit. 
The appropriate personnel from the study center and CRO will assess whether the study treatment 
should be discontinued for any subject whose treatment code has been broken inadvertently for 
any reason. 
The Investigator must also contact the IWRS to register the subject’s discontinuation from the 
study treatment. 
7.3 
Lost to Follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study center. 
The following actions must be taken if a subject fails to return to the study center for a required 
study visit: 


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• The study center must attempt to contact the subject and reschedule the missed visit as soon 
as possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in the 
study. 
• Before a subject is deemed lost to follow-up, the Investigator or designee must make every 
effort to regain contact with the subject (where possible, 3 telephone calls and, if necessary, 
a certified letter to the subject’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the subject’s medical record. 
• Should the subject continue to be unreachable, he/she will be considered to have withdrawn 
from the study.  
 
 




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45 
8.1.1 
Assessments for Scalp:  
8.1.1.1 
Investigator Global Assessment (IGA) mod 2011 rating scale (Scalp) 
The IGA mod 2011 is a 
scale that is static 
 
 
 This scale met the evidence standard 
for pivotal trials, and has supported previous product labeling claims
 
 
 
 
 
 
 
 
8.1.1.2 
Investigator Global Assessment (Scalp only) 
The 
 IGA score is a useful clinician assessment of scalp lesions based on thickness, 
erythema, and scaling that is here retained as a secondary endpoint
 
 
 
 
 
 
 
 
 
 
 
 
8.1.1.5 
Psoriasis Scalp Severity Index (PSSI) 
The PSSI is a modification of the PASI to specifically assess severity of scalp disease. The PSSI 
use a 
 scale to grade the 3 clinical parameters
 in the same 
way as the PASI, but for scalp only.
 
8.1.2 
Assessments for Whole Body:  
8.1.2.1 
Investigator Global Assessment (IGA) mod 2011 rating scale (whole body) 
The IGA mod 2011 is a 
scale
 
 


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46 
This scale met the evidence standard 
for pivotal trials, and has supported previous product labeling claims 
 
 
 
 
 
 
 
8.1.2.2 
Physician Global Assessment of Skin (Whole body) 
The PGA-S is a 
 useful clinician assessment of psoriasis lesions on 
the skin based on degree of erythema, thickness, and scale averaged over the entire body. 
 
 
8.1.2.3 
Psoriasis Area and Severity Index 
Psoriasis Area and Severity Index will be used to determine the treatment response (PASI 75, PASI 
90, and PASI 100) in subjects with scalp psoriasis. 
 
8.1.2.4 
Body Surface Area 
Body Surface Area is a commonly used measure of severity of skin disease. It is defined as the 
percentage of the total BSA affected by psoriasis, it represents the area of affected scalp. 
 
 
 
 
8.1.3 
Dermatology Life Quality Index 
The DLQI questionnaire will be used to assess treatment response on the subject’s quality of life. 
The aim of this questionnaire is to measure how much the skin condition has affected the subject’s 
life during the previous week.  
 
 
The questionnaire is self-explanatory and handed to the subject who is asked to fill it 
in without the need for a detailed explanation 
 
8.2 
Safety Assessments  
 






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Protocol TILD-18-20- 
  
 
 
• A central laboratory will be used to perform all laboratory tests except urine pregnancy 
dipstick which will be assessed by the center staff. However, local laboratory tests will be 
allowed in the event that the central laboratory results will not be available immediately 
and the Investigator needs to take an immediate decision for any safety concerns based on 
the laboratory results.  
• The Investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those that are not associated with the underlying disease, unless 
judged by the Investigator to be more severe than expected for the subject’s condition. 
• All laboratory tests with values considered clinically significantly abnormal during 
participation in the study including the subject’s last EoS visit should be repeated until the 
values return to normal or Baseline or until stabilized or are no longer considered clinically 
significant by the Investigator or Medical Monitor. 
If such values do not return to normal/Baseline within a period of time judged reasonable by the 
Investigator, the etiology should be identified, if possible and the Sponsor notified. 
All protocol-required laboratory assessments,
 must be conducted in 
accordance with the Laboratory Manual 
  
8.3 
Adverse Events 
The safety and tolerability of subjects will be assessed by the incidence of treatment-emergent 
adverse events (TEAEs), laboratory test results, vital signs, ECGs, and physical examination 
findings. 
The definitions of an AE or SAE can be found in Appendix 4. 
The Investigator will document all AEs in the subject’s source document and eCRF. All entries 
should contain an event term, date of onset, date of resolution, severity, action taken, outcome, 
relationship to study treatment, and a seriousness assessment. 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information  
Any relevant observations made before the end of the Screening and Baseline visit (prior to first 
dose of study treatment) are to be recorded on the AE eCRF, but will not be considered TEAEs 
and will be reported separately from TEAEs. Any relevant observations made after the first dose 
of study treatment will be recorded as an AE in the subject’s AE eCRF 
 
 
 
For the purposes of this study, any detrimental change in the subject’s condition, 
after the first dose of study treatment and up to completion of the EoS visit, should be considered 


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50 
an AE. For those subjects who may withdraw during the Observational Safety Follow-up Period 
or wash-out period, at least 2 attempts should be made to collect the AEs. 
A hospitalization planned by the subject prior to signing the ICF is considered a therapeutic 
intervention and not the result of a new SAE and should be recorded as medical history. If the 
planned hospitalization or procedure is executed as planned, the record in the subject’s medical 
history is considered complete. However, if the event/condition worsens during the study, it must 
be reported as an AE. 
Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the AE section of the eCRF, however will not be considered as TEAEs.  
All SAEs will be recorded and reported to the CRO within 24 hours, as indicated in Appendix 4. 
The Investigator will submit any updated SAE data to the CRO within 24 hours of it being 
available. The Investigator is responsible for informing the Ethics Committee of the SAE as per 
local requirements. All AEs/SAEs have to be reported to the Sponsor, whether or not considered 
causally related to the study treatment or to the study procedures. 
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a subject has been discharged from the study, and he/she considers the event to be reasonably 
related to the study treatment or study participation, the Investigator must promptly notify the CRO. 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 4. 
8.3.2 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrences.  
8.3.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs, and non-serious AEs of special interest (as defined in Section 
8.3.6), will be followed until resolution, stabilization, the event is otherwise explained, or the 
subject is lost to follow-up (as defined in Section 7.3). Further information on follow-up 
procedures is given in Appendix 4. 
8.3.4 
Regulatory Reporting Requirements for SAEs 
All SAEs must be reported according to ICH GCP or local regulations, applying the regulation 
with the stricter requirements. The report will contain as much available information concerning 
the SAE to enable the Sponsor’s designated pharmacovigilance personnel/ CRO to file a report, 


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which satisfies regulatory reporting requirements. The SAE report will be notified by Investigator 
within 24-hours of his/her awareness to the Sponsor’s designated pharmacovigilance 
personnel/CRO. These timelines apply to initial reports of SAEs and to all follow-up reports. 
All SAEs will be recorded on the SAE report form in the eCRF and source documents. 
The following minimum information must be included in the SAE form: 
• Name, address and telephone number of the reporting Investigator 
• Study treatment details 
• Subject identification number, initials, sex and date of birth 
• Description of the SAE, measures taken and outcome 
Relevant pages from the eCRF may be provided in parallel (eg, medical history, concomitant 
drugs). Additional documents may be provided by the Investigator, if available (eg, laboratory 
results, hospital report, autopsy report).  
The Investigator must respond to any request for follow-up information (eg, additional 
information, outcome, final evaluation, other records where needed) or to any question the 
Sponsor’s designated pharmacovigilance personnel/CRO may have on the SAE. This is necessary 
to ensure prompt assessment of the event by the Sponsor’s designated pharmacovigilance 
personnel to allow the Sponsor to meet strict regulatory timelines associated with expedited safety 
reporting obligations. 
8.3.5 
Pregnancy 
Pregnancy itself is not regarded as an AE unless there is suspicion that the study treatment may 
have interfered with the effectiveness of a contraceptive medication. If a pregnancy is reported for 
a subject, no further study treatment will be administered to this subject and the outcome of all 
pregnancies (spontaneous miscarriage, elective termination, normal birth or congenital 
abnormality) must be followed up and documented. Follow-up should be performed up to delivery 
and examination of the newborn, after which a follow-up report should be sent with any new 
information regarding the pregnancy and the outcome of the birth. 
The pregnancy shall be followed every 3 months during pregnancy until its outcome and 1 month 
post-delivery. If there are abnormalities present at delivery, the newborn will be followed for an 
appropriate period, or up to 3 months, to assess the functional and health status of the child. 
All congenital abnormalities/birth defects should be classified as SAEs. Spontaneous miscarriages 
should also be reported and handled as SAEs. Elective abortions without complications should not 
be handled as SAEs but should be reported as a follow-up report for the pregnancy. All outcomes 
of pregnancy must be reported to the Sponsor on a Pregnancy Outcomes Report Form. 


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52 
Pregnancy outcomes must be collected for the female partners of any males who took study 
treatment in this study. Consent to report information regarding these pregnancy outcomes should 
be obtained from the female partner. 
Pregnancies must be reported to Novella Clinical Pharmacovigilance and Safety Services using 
the reporting details provided in Appendix 4 within 24 hours of becoming aware of the pregnancy. 
8.3.6 
Adverse Events of Special Interest 
The events of severe infections, injection site reactions (e.g. pain, edema, erythema), malignancies 
(including non-melanoma and melanoma skin cancer), Major Adverse Cardiovascular Events, and 
study treatment -related hypersensitivity reactions (see Appendix 5) will be identified as adverse 
events of special interest (AESIs) for summarizing in this study. Major Adverse Cardiovascular 
Events include non-fatal stroke, non-fatal myocardial infarction and cardiovascular death. An 
AESI must be reported as if it were an SAE. 
8.3.7 
Events of Clinical Interest 
An Event of Clinical Interest (ECI) is a non-serious AE or occurrence that is designated to be of 
special interest and must be reported to the Sponsor as though it were an SAE. 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.4 
Treatment of Overdose 
A drug overdose is defined as the accidental or intentional use of a drug or medicine or an 
administration error in an amount that is higher than is normally used.
 
 
Overdose in this study is specifically defined as any dose greater than the intended protocol dose 
In case of overdose, it is recommended that the subject be monitored for any signs 


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53 
or symptoms of adverse reactions or effects and appropriate symptomatic treatment be instituted 
immediately. 
8.5 
Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.7 
Genetics 
Genetics are not evaluated in this study. 
8.8 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.9 
Health Economics or Medical Resource Utilization and Health Economics 
Health Economics/Medical Resource Utilization and Health Economics parameters are not 
evaluated in this study. 
 
 




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55 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
9.3 
 Populations for Analyses 
For purposes of analysis, the analysis sets in Table 3 are defined. 


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Table 3 
Analysis Sets 
Analysis Set 
Description 
Intent-to-Treat (ITT) 
All randomized subjects who have received 
 dose of study 
treatment 
 
 
Subjects will be analyzed according to their planned treatment 
assignment. 
Per Protocol Set (PPS) 
All subjects in the ITT population who complete the 
 placebo-
controlled treatment 
 
 
 
 
 
 
Safety Analysis Set (SAS) 
All randomized subjects who receive 
 dose of study 
treatment.  Subjects will be analyzed according to the treatment they 
actually received. Safety endpoints will be analyzed descriptively 
based on the SAS. 
9.4 
Statistical Analyses 
The statistical analysis will be performed using statistical analysis system (SAS®) Version 9.3 or 
higher if available. All details regarding the statistical analysis and the preparation of tables, 
listings and figures will be described in the Statistical Analysis Plan (SAP). The SAP will be 
developed and finalized before database lock after the completion of the 
 
placebo-controlled treatment period. This section is a summary of the planned statistical analyses 
of the primary and secondary endpoints. 
The following descriptive statistics will be used as applicable to summarize the study data unless 
otherwise specified: 
• Continuous variables: sample size (n), mean, standard deviation (SD), median, minimum 
(min), and maximum (max). 
• Categorical variables: frequencies and percentages. 
Unless otherwise specified, “Baseline” is defined as the last observed value of the parameter of 
interest prior to the first intake of study treatment (this includes unscheduled visits).
 
 
 
 
 








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tabulated for each treatment arm. Commonly occurring TEAEs,
 
 in either treatment arm, will be summarized using descriptive statistics. 
The safety of tildrakizumab will be evaluated by and reported as the percentage of subjects for 
the following TEAEs: 
• Incidence, seriousness and severity of all AEs, death cases and discontinuations from the 
study. 
• Percentage of subjects with severe infections, defined as any infection meeting the 
regulatory definition of a serious adverse event, or any infection requiring IV antibiotics 
whether or not reported as a serious event as per the regulatory definition. 
• Percentage of subjects with malignancies (excluding carcinoma in situ of the cervix). 
• Percentage of subjects with non-melanoma skin cancer. 
• Percentage of subjects with melanoma skin cancer. 
• Percentage of subjects with MACE 
 
• Percentage of subjects with study treatment-related hypersensitivity reactions (eg, 
anaphylaxis, urticaria, angioedema, etc). 
• Percentage of subjects with injection site reactions (eg, pain, erythema, edema, etc). 
9.4.2.2 
Physical Examinations, 12-Lead ECG, Vital Signs and Clinical Safety 
Laboratory Tests (Hematology, Biochemistry, and Urinalysis) 
Summaries and listings of data for physical examination findings, vital signs, hematology, 
biochemistry, and urinalysis laboratory tests will be presented. Appropriate descriptive statistics 
will be summarized for the observed value at each scheduled assessment and for the 
corresponding change from Baseline. 
For hematology and biochemistry tests, listings of subject data will also flag up any abnormal or 
out-of-range values. Clinically significant changes in the laboratory test parameters will be 
summarized and listed. Hematology and clinical laboratory data will be reported in System 
International units. 
Descriptive statistics will be used to present the safety outcomes including, physical examination 
results, weight, body mass index, 12-Lead ECG, vital signs measurements, and clinical 
laboratory test results. 
Change from Baseline will also be summarized for vital signs measurements and clinical 
laboratory test results. 
All ECG data results (normal/abnormal) will be summarized using frequency and percentages. 
Clinically significant abnormalities will be presented in by-subject listings. 








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APPENDIX 2: 
REGULATORY, ETHICAL AND STUDY OVERSIGHT 
CONSIDERATIONS 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences International Ethical Guidelines. 
o Applicable International Council for Harmonisation Good Clinical Practice (ICH 
GCP) Guidelines. 
o Applicable laws and regulations. 
• The protocol, protocol amendments, informed consent form (ICF), Investigator Brochure, 
and other relevant documents (eg, advertisements) must be submitted to an IRB/IEC by 
the Investigator and reviewed and approved by the Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC) before the study is initiated.  
• Any amendments to the protocol will require IRB/IEC and regulatory authority approval, 
when applicable, before implementation of changes made to the study design, except for 
changes necessary to eliminate an immediate hazard to subjects.  
• The Investigator will be responsible for the following: 
o 
Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
o 
Notifying the IRB/IEC of serious adverse events (SAEs) or other significant safety 
findings as required by IRB/IEC procedures. 
o 
Providing oversight of the conduct of the study at the study center and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, 
European regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations. 
o 
After reading the protocol, each Investigator will sign the protocol signature page and 
send a copy of the signed page to the Sponsor or representative (see Appendix 20). 
o 
The study will not start at any study center at which the Investigator has not signed 
the protocol. 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 


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responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
Insurance 
Sponsor will provide insurance in accordance with local guidelines and requirements as a 
minimum for the subjects in this study. The terms of the insurance will be kept in the study files. 
Informed Consent Process 
• The Investigator or his/her representative will explain the nature of the study to the 
subject or his/her legally authorized representative and answer all questions regarding the 
study.  
• Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorized representative will be required to sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health 
Insurance Portability and Accountability Act (HIPAA) requirements, where applicable, 
and the IRB/IEC or study center.  
• The medical record must include a statement that written informed consent was obtained 
before the subject was entered in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF. 
• Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study.  
• A copy of the ICF(s) must be provided to the subject or the subject’s legally authorized 
representative.  
• A subject who is rescreened is not required to sign another ICF if the rescreening occurs 
within 30 days from the previous ICF signature date. 
Data Protection 
• Subjects will be assigned a unique identifier by the Sponsor. Any subject records or 
datasets that are transferred to the Sponsor will contain the identifier only; subject names 
or any information which would make the subject identifiable will not be transferred.  
• The subject must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also 
be explained to the subject.  
• The subject must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
 


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Quality Control and Quality Assurance 
 
 


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 Quality control will be applied to each stage of data 
handling. 
The following steps will be taken to ensure the accuracy, consistency, completeness, and 
reliability of the data: 
• Central laboratories for clinical laboratory parameters. 
• Study center Initiation visit. 
• Early study center visits post-enrollment. 
• Routine study center monitoring. 
• Ongoing study center communication and training. 
• Data management quality control checks. 
• Continuous data acquisition and cleaning. 
• Internal review of data. 
• Quality control check of the final clinical study report (CSR). 
In addition, Sponsor 
may conduct periodic audits 
of the study processes, including, but not limited to study center, central laboratories, vendors, 
clinical database, and final CSR. When audits are conducted, access must be authorized for all 
study-related documents including medical history and concomitant medication documentation 
to authorized Sponsor’s representatives and regulatory authorities. 
Monitoring 
Sponsor has engaged the services of a contract research organization,
 to perform all 
monitoring functions within this clinical study. 
monitors will work in accordance with 
SOPs. The monitor will establish and maintain regular contact between the Investigator 
and Sponsor. 
The monitor will evaluate the competence of the study center, informing Sponsor about any 
problems relating to facilities, technical equipment, or medical staff. During the study, the 
monitor will check that written informed consent has been obtained from all subjects correctly 
and that data are recorded correctly and completely. The monitor is also entitled to compare 
entries in the eCRFs with corresponding source data and to inform the Investigator of any errors 
or omissions. The monitor will also assess and control adherence to the protocol and ICH/GCP 
guidelines at the study center. The monitor will arrange for the supply of study treatment, ensure 
proper study treatment dispensing/accountability, and appropriate storage conditions are 
maintained. 
Monitoring visits will be conducted according to all applicable regulatory requirements and 
standards. Regular monitoring visits will be made to each center while subjects are enrolled in 
the study.  


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During monitoring visits, all entries in the eCRFs will be compared with the original source 
documents (source data verification). For the following and all other items, this check will be 
100%: 
• Subject identification number. 
• Subject consent obtained. 
• Subject eligibility criteria (inclusion and exclusion criteria). 
• Efficacy variables (not directly entered into PRO). 
• Safety variables. 
• Medical record of AE. 
Quality Management 
A system should be implemented to manage quality throughout all stages of the study process 
with the focus on study activities essential to ensuring human subject protection and the 
reliability of study results. The methods used to assure and control the quality of the clinical 
study should be proportionate to the risks inherent in the trial and the importance of the 
information collected. All aspects of the study should be operationally feasible and should avoid 
unnecessary complexity, procedures, and data collection.  
During protocol development, processes and data that are critical to ensure human subject 
protection and the reliability of trial results should be identified. Risks should be considered at 
both the system level (eg, standard operating procedures, computerized systems, personnel) and 
clinical trial level (eg, trial design, data collection, informed consent process). The approach used 
to reduce risk to an acceptable level should be proportionate to the significance of the risk. 
Predefined quality tolerance limits should be established, taking into consideration the medical 
and statistical characteristics of the variables as well as the statistical design of the trial, to 
identify systematic issues that can impact subject safety or reliability of trial results. Detection of 
deviations from the predefined quality tolerance limits should trigger an evaluation to determine 
if action is needed. 
Quality management activities should be documented and communicated to those who are 
involved in or affected by such activities, to facilitate risk review and continual improvement 
during clinical trial execution. 
Data Management/Coding 
 
 
Electronic data capture will be used for this study, meaning that all eCRF data will be entered in 
electronic forms at the study centers. Data collection will be completed by authorized study 
center staff designated by the Investigator. Appropriate training and security measures will be 


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completed with the Investigator and all designated study center staff prior to the study being 
initiated and any data being entered into the system for any study subjects. 
All data must be entered in English. The eCRFs should always reflect the latest observations on 
the subjects participating in the study. Therefore, the eCRFs are to be completed as soon as 
possible during or after the subject’s visit. To avoid inter-observer variability, every effort should 
be made to ensure that the same individual who made the initial Baseline determinations 
completes all efficacy and safety evaluations. The Investigator must verify that all data entries in 
the eCRFs are accurate and correct. If some assessments are not done, or if certain information is 
not available or not applicable or unknown, the Investigator should indicate this in the eCRF. 
The Investigator will be required to electronically sign off on the clinical data when all the data 
is clean prior to database lock. 
The monitor will review the eCRFs and evaluate them for completeness and consistency. The 
eCRF will be compared with the source documents to ensure that there are no discrepancies 
between critical data. The monitor cannot enter data in the eCRFs. All entries, corrections and 
alterations are to be made by the responsible Investigator or his/her designee. If additional 
corrections are needed, the responsible monitor or Data Manager will raise a query in the EDC 
application. The appropriate study center staff will answer queries sent to the Investigator. This 
will be audit trailed by the EDC application meaning that the name of investigational staff, time, 
and date stamp are captured. 
The eCRF is essentially considered a data entry form and should not constitute the original (or 
source) medical records unless otherwise specified. Source documents are all documents used by 
the Investigator or hospital that relate to the subject’s medical history, that verify the existence of 
the subject, the inclusion and exclusion criteria and all records covering the subject’s 
participation in the study. They include but are not limited to laboratory notes, ECG results, 
memoranda, pharmacy dispensing records, subject files, etc. Source data should be attributable, 
legible, contemporaneous, original, accurate, and complete. Any changes to the source 
documents or cancellations should be signed and initialed with date. Changes to source data 
should be traceable, should not obscure the original entry, and should be explained if necessary 
(eg, via an audit trail). 
The Investigator is responsible for maintaining source documents. These will be made available 
for inspection by the study monitor at each monitoring visit. The Investigator must submit a 
completed eCRF for each subject who is screened and enrolled in the study regardless of 
duration. All supportive documentation submitted with the eCRF, such as laboratory or hospital 
records, should be clearly identified with the study and subject number. Any personal 
information, including subject name, should be removed or rendered illegible to preserve 
individual confidentiality. 


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User Roles and Responsibilities:  
Once clinical data of the eCRF have been submitted to the central server, corrections to the data 
fields will be audit trailed, meaning that the reason for change, the name of the person who 
performed the change, together with time and date will be logged. Roles and rights of the study 
center staff responsible for entering the clinical data into the eCRF will be determined in 
advance. 
Electronic CRF records will be automatically appended with the identification of the creator, by 
means of their unique User ID. Specified records will be electronically signed by the Investigator 
to document his/her review of the data and acknowledgement that the data are accurate. This will 
be facilitated by means of the Investigator’s unique User ID and password; date and time stamps 
will be added automatically at time of electronic signature.  
Data Handling and Record Keeping 
The Investigator must maintain essential study documents (protocol and protocol amendments, 
completed eCRFs, signed ICFs, relevant correspondence, and all other supporting 
documentation). The study center should plan on retaining such documents for approximately 
15 years after study completion. The study center should retain such documents until at least 
2 years after the last approval of a marketing application in an ICH region and until there are no 
pending or contemplated marketing applications in an ICH region or at least 2 years after the 
formal discontinuation of clinical development of the study treatment. These documents should 
be retained for a longer period if required by the applicable regulatory requirements or the 
hospital, institution, or private practice in which the study is being conducted. Subject 
identification codes (subject names and corresponding study numbers) will be retained for this 
same period of time. These documents may be transferred to another responsible party, 
acceptable to Sponsor, who agrees to abide by the retention policies. Written notification of 
transfer must be submitted to Sponsor. The Investigator must contact Sponsor prior to disposing 
of any study records. 
Direct Access to Source Documents 
The Investigator will prepare and maintain adequate and accurate source documents to record all 
observations and other pertinent data for each subject randomized into the study. 
The Investigator will allow Sponsor, 
 and authorized regulatory authorities to have direct 
access to all documents pertaining to the study, including individual subject medical records, as 
appropriate. Such information must be kept confidential and must have locked facilities that 
allow for this. Subject identification number will be recorded on all documents related to the 
study. 
 


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Study and Study Center Closure 
The Sponsor designee reserves the right to close the study center or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study centers will be closed upon study 
completion. A study center is considered closed when all required documents and study supplies 
have been collected and a study center closure visit has been performed. 
The Investigator may initiate study center closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study center by the Sponsor or Investigator may include but 
are not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the Sponsor’s procedures, or GCP guidelines. 
• Inadequate recruitment of subjects by the Investigator. 
• Discontinuation of further study treatment development. 
Publication Policy 
The data generated by this study are confidential information of the Sponsor. The Sponsor will 
make the results of the study publicly available. The publication policy with respect to the 
Investigator and study center will be set forth in the Clinical Trial Agreement. 
 
 
 
 
 
 
 
 
 
 
 
 


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APPENDIX 4: 
ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a patient or subject, temporally associated with the use 
of study treatment, whether or not considered related to the study treatment. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of 
study treatment. 
Events Meeting the AE Definition  
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (eg, ECG, radiological scans, vital signs measurements), including those that worsen from 
Baseline, considered clinically significant in the medical and scientific judgment of the Investigator 
(ie, not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even though it may have 
been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an intentional 
overdose taken with possible suicidal/self-harming intent. Such overdoses should be reported 
regardless of sequelae. 
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported as an AE 
or SAE. Such instances will be captured in the efficacy assessments. However, the signs, symptoms, 
and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if they fulfill the 
definition of an AE or SAE. 
 


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Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments which are 
associated with the underlying disease, unless judged by the Investigator to be more severe than 
expected for the subject’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the disease/disorder 
being studied, unless more severe than expected for the subject’s condition. 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at the 
start of the study that do not worsen. 
• 
Pregnancy itself is not regarded as an AE unless there is suspicion that the study treatment may have 
interfered with the effectiveness of a contraceptive medication. If a pregnancy is reported for a subject, 
no further study treatment will be administered to this subject and the outcome of all pregnancies 
(spontaneous miscarriage, elective termination, normal birth or congenital abnormality) must be 
followed up and documented. Follow-up should be performed up to delivery and examination of the 
newborn, after which a follow-up report should be sent with any new information regarding the 
pregnancy and the outcome of the birth. 
• 
All congenital abnormalities/birth defects should be classified as SAEs. Spontaneous miscarriages 
should also be reported and handled as SAEs. Elective abortions without complications should not be 
handled as SAEs but should be reported as a follow-up report for the pregnancy. All outcomes of 
pregnancy must be reported to the Sponsor on a Pregnancy Outcomes Report Form. 
• 
Pregnancy outcomes must be collected for the female partners of any males who took study treatment 
in this study. Consent to report information regarding these pregnancy outcomes should be obtained 
from the female partner. 
• 
The pregnancy shall be followed every 3 months during pregnancy till its outcome and 1 month post-
delivery. If there are abnormalities present at delivery, the newborn will be followed for an appropriate 
period, or up to 3 months, to assess the functional and health status of the child. 
• 
Pregnancies must be reported to 
 using the 
reporting details provided in Section 8.3.4within 24 hours of awareness. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
An SAE is defined as, but is not limited to, an event that: 
a) Results in death 
Death is not an AE in itself, but an outcome. The cause of the death is the AE which resulted in death. 
b) Is life-threatening 
Life-threatening means that the subject was at immediate risk of death at the time of the SAE; it does not 
refer to an SAE that hypothetically might have caused death if it had been more severe. . 


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c) Requires inpatient hospitalization or prolongation of existing hospitalization 
Hospitalization is defined as at least 1 overnight formal admission into hospital, usually in order to perform 
additional tests, provide treatment which it is not possible to provide at home and/or due to an unstable 
medical condition which requires specific monitoring of the subject. Pre-planned hospitalizations (known 
already prior to signing the ICF) for pre-existing condition, or a procedure required by the Clinical 
Investigation Plan, without a serious deterioration in health or if the hospitalization is clearly not associated 
with an AE (eg, social hospitalization) will not be considered an SAE, unless any of the above criteria are 
fulfilled over the course of the hospitalization due to unplanned complications. Any Hospitalization due to 
logistic reason will not be considered as SAE” “Social” hospitalization whereby it is administratively 
impossible to release the subject home is not necessarily an SAE. Complications that occur during 
hospitalizations are AEs unless they would qualify as an SAE for any of the above criteria. If the 
complication delays subject release from hospital, then the AE becomes an SAE. Hospitalizations which 
are not performed due to an AE are not regarded as SAEs. 
d) Results in persistent or significant disability/incapacity 
The term significant disability refers to any condition that impairs physical/physiological well-being to the 
extent that the subject is unable to function normally. Physical disability may include, but is not limited to, 
permanent disability of locomotion or motility, but also systemic permanent dysfunction including heart 
failure, liver insufficiency or pulmonary fibrosis. 
e) Is a congenital anomaly/birth defect 
f) 
Is an important medical event: 
Important medical events that may not result in death, be life-threatening or require hospitalization may be 
considered as an SAE when, based on appropriate medical judgment, they may jeopardize the subject, or 
the subject may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. 


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Recording and Follow-up of AE and/or SAE 
Definition of the Adverse Event Reporting Period 
The AE/ SAE reporting period for safety surveillance begins after subject signs ICF. The safety 
surveillance continues until 20 weeks from last dose of study treatment administration. Any 
AE/-SAE occurred post 20 weeks from last dose of study treatment administration will be 
reported if it is considered related to study treatment by the Investigator. 
Unexpected Adverse Event 
Any adverse event that is not identified in nature, severity, frequency or outcome in Investigator 
Brochure (IB) will be considered as unexpected. Most recent version of IB will serve as 
reference safety information for assessment of expectedness of SAEs. 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation (eg, 
hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The Investigator will then record all relevant AE/SAE information in the eCRF. Each event must be 
recorded separately. 
• 
It is not acceptable for the Investigator to send photocopies of the subject’s medical records to 
 
 in lieu of completion of the/AE/SAE eCRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by 
 
. In this case, all subject identifiers, with the exception 
of the subject number, will be redacted on the copies of the medical records before submission to 
. 
• 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) will 
be documented as the AE/SAE. 
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the study and 
assign it to 1 of the following categories:  
• 
Mild: An event that is easily tolerated by the subject, causing minimal discomfort and not interfering 
with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe should not 
be confused with a SAE. Severe is a category utilized for rating the intensity of an event; and both AEs 
and SAEs can be assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as described in the 
definition of an SAE, NOT when it is rated as severe. 
 


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Assessment of Causality 
• 
The Investigator is obligated to assess the relationship between study treatment and each occurrence of 
each AE/SAE. The AE must be characterized as certainly/definitely related, unrelated, unlikely to be 
related, possibly related, or probably related. 
o 
“Certainly/definitely related” suggests that a clinical event, including laboratory test 
abnormality, occurring in a plausible time relationship to drug administration, and which 
cannot be explained by concurrent disease or other drugs or chemicals. The response to 
withdrawal of the drug (de-challenge) should be clinically plausible. The event must be 
definitive pharmacologically or phenomenologically, using a satisfactory re-challenge 
procedure if necessary. 
o 
“Probably related” conveys that there are facts, evidence, and/or arguments to suggest a 
causal relationship, rather than a relationship cannot be ruled out. 
o 
“Possibly related” suggests that the association of the AE with the study treatment is 
unknown; however, the AE is not reasonably supported by other conditions. 
o 
“Unlikely to be related” suggests that only a remote connection exists between the study 
treatment and the AE. Other conditions, including chronic illness, progression or expression 
of the disease state or reaction to concomitant therapy, appear to explain the reported AE. 
o 
“Unrelated” is used if there is not a reasonable possibility that the study treatment caused the 
AE.  
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well 
as the temporal relationship of the event to study treatment administration will be considered and 
investigated. 
• 
The Investigator will also consult the IB and/or Product Information, for marketed products, in his/her 
assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred, and the Investigator has minimal information 
to include in the initial report to 
. However, it 
is very important that the Investigator always make an assessment of causality for every event before 
the initial transmission of the SAE data to 
. 
• 
The Investigator may change his/her opinion of causality in light of follow-up information and send a 
SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
Action Taken with respect to study treatment 
Action taken is categorized as “none”, “study treatment discontinued permanently”, “study treatment 
discontinued temporarily and restarted”, or unknown. 
Event Outcome 
Event outcome recorded and categorized as “Fatal”, “Resolved”, “Resolved with sequelae”, “Resolving”, 
“Not Resolved”, or “Unknown”. 
 


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Follow-up of AEs and SAEs 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by 
 
 to elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or consultation 
with other health care professionals. 
• 
If a subject dies during participation in the study or during a recognized follow-up period, the 
Investigator will provide 
 with a copy of any postmortem findings including 
histopathology.  
• 
New or updated information will be recorded in the originally completed eCRF. 
• 
The Investigator will submit any updated SAE data to the 
 
 within 24 hours of receipt of the information. 
Follow-up of unresolved AEs and SAEs 
Any AE/ SAE unresolved at end of study visit will be followed until resolution/ stabilization or as per 
medical judgment of the Investigator. 
 
Reporting of SAEs 
SAE Reporting to 
 via Paper Case Report 
Form (CRF) 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this information to 
the 
 
• 
In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the SAE data collection tool sent by overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the Investigator to complete and sign the 
SAE CRF pages within the designated reporting time frames. 
Safety Reporting to Sponsor 
• 
 will forward the SAE and Pregnancy report to 
the Sponsor’s safety representatives within 1 business day or 3 calendar days (whichever is earlier) of 
becoming aware of it. 
 
 




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APPENDIX 6: 
EXCLUDED MEDICATIONS/THERAPY 
Excluded medications/therapy is listed below. The concomitant use of an excluded 
medication/therapy with study treatment is not in compliance with the study protocol and must 
be recorded in the eCRF. 
 
 
   
 
 
  
 
 
 
 
  
 
 


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APPENDIX 7: 
CONTRACEPTIVE GUIDANCE AND COLLECTION OF 
PREGNANCY  
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP 
6. Premenarchal 
7. Premenopausal female with 1 of the following: 
a) Documented hysterectomy. 
b) Documented bilateral salpingectomy. 
c) Documented bilateral oophorectomy. 
Note: Documentation can come from the study center personnel’s: review of the subject’s 
medical records, medical examination, or medical history interview. 
8. Postmenopausal female: 
a) A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient.  
b) Females on HRT and whose menopausal status is in doubt will be required to use 1 of the 
non-estrogen hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation 
of postmenopausal status before study enrollment. 
Contraception Guidance 
Male subjects 
• Male subjects with female partners of childbearing potential are eligible to participate if they 
agree to 1 of the following during the study and for 6 months after the last dose of study 
treatment:  
o Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent. 
o Agree to use a male condom plus partner use of a contraceptive method with a failure 
rate of <1% per year when having penile-vaginal intercourse with a woman of 
childbearing potential who is not currently pregnant. 


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• In addition, male subjects must refrain from donating sperm for the duration of the study and 
for 6 months after the last dose of study treatment. 
• Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile penetration 
for the duration of the study and for 6 months after the last dose of the study treatment. 
Female subjects 
Female subjects of childbearing potential are eligible to participate if they agree to use a highly 
effective method of contraception consistently and correctly as described in the table below. 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a  
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulationb  
• 
Oral.  
• 
Intravaginal.  
• 
Transdermal. 
Progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Oral. 
• 
Injectable.  
Highly Effective Methods That Are User Independent a  
Implantable progestogen only hormonal contraception associated with inhibition of ovulationb 
• 
Intrauterine device (IUD). 
• 
Intrauterine hormone-releasing system (IUS). 
Bilateral tubal occlusion. 
Vasectomized partner  
A vasectomized partner is a highly effective birth control method provided that the partner is the sole male sexual 
partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method 
of contraception should be used.  
Sexual abstinence  
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the subject.  
NOTES:  
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent with 
local regulations regarding the use of contraceptive methods for subjects participating in clinical studies.  
b Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce the efficacy 
of the contraceptive method. In this case, 2 highly effective methods of contraception should be utilized during 
the treatment period and for at least 6 months, after the last dose of study treatment.  




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Investigator is not obligated to actively seek this information in former subjects, he or she 
may learn of an SAE through spontaneous reporting.  
• Any female subject who becomes pregnant while participating in the study will discontinue 
study treatment or be withdrawn from the study. 
• The pregnancy shall be followed every 3 months during pregnancy till its outcome and one 
month post-delivery. If there are abnormalities present at delivery, the newborn will be 
followed for an appropriate period, or up to 3 months, to assess the functional and health 
status of the child. 
 
 


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APPENDIX 19: 
COLUMBIA-SUICIDE SEVERITY RATING SCALE 
1) C-SSRS Screening 
 


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2) C-SSRS Baseline  






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3) C-SSRS Since Last Visit 
 


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SAP_001.pdf: 
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled clinical study 
to assess the efficacy and safety of Tildrakizumab in the treatment of moderate to severe 
plaque psoriasis of the scalp 
 
Document: Statistical Analysis Plan (SAP) 
 
NCT number: NCT03897088 
 
Date: 30-Mar-2022 


Statistical Analysis Plan 
 
 
         Sun Pharmaceutical Industries Ltd 
Protocol TILD-18-20 
 
30-Mar-2022 
 
CONFIDENTIAL 
1 
 
 
1 
 
2 
Statistical Analysis Plan 
3 
Study Part 1: Interim Analysis (up to Week 16) 
4 
Study Part 2: Double Blind (Week 16 to Week 52) 
5 
Study Part 3: Observational Safety Follow-Up (Week 52 to Week 72) 
6 
 
7 
A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED 
8 
CLINICAL STUDY TO ASSESS THE EFFICACY AND SAFETY OF TILDRAKIZUMAB 
9 
IN THE TREATMENT OF MODERATE TO SEVERE PLAQUE PSORIASIS OF THE 
10 
SCALP 
11 
 
12 
 
13 
Protocol Number: TILD-18-20 
14 
 
15 
 
16 
IND Number: 101389 
17 
 
18 
Date:  30-Mar-2022  
19 
 
20 
 
21 
 
22 
Confidentiality Statement 
23 
The information disclosed in connection with this Clinical Study Report is the trade secret, confidential, 
24 
privileged and/or proprietary financial or commercial information of Sun Pharmaceutical Industries Ltd. and is 
25 
delivered in confidence and reliance that it will not be copied or made available to any third party without the 
26 
prior written consent of Sun Pharmaceutical Industries Ltd. except as may be required by federal, state, or local 
27 
laws or regulations.  Sun Pharmaceutical Industries Ltd. requests that this information be treated as privileged 
28 
or confidential trade secret, commercial or financial information in accordance with 5 U.S. Code, sec. 
29 
552(b)(4), and that it be provided with prior written notice of any disclosure required by law.  
30 
 
31 






Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
4 
Table of Contents 
95 
STATISTICAL ANALYSIS PLAN ........................................................................................1 
96 
STATISTICAL ANALYSIS PLAN SIGNATURES .............................................................2 
97 
 
SUMMARY OF CHANGES .........................................................................................3 
98 
TABLE OF CONTENTS .........................................................................................................4 
99 
LIST OF ABBREVIATIONS ..................................................................................................7 
100 
1 
INTRODUCTION .........................................................................................................9 
101 
2 
STUDY OBJECTIVES ...............................................................................................10 
102 
2.1 
Primary Objective .......................................................................................................10 
103 
2.2 
Secondary Objectives .................................................................................................10 
104 
2.3 
Exploratory Objective ................................................................................................11 
105 
3 
OVERALL STUDY DESIGN AND TREATMENT PLAN ....................................11 
106 
4 
STATISTICAL CONSIDERATIONS OF PROTOCOL .........................................13 
107 
4.1 
General Statistical Consideration ...............................................................................13 
108 
4.1.1 
Baseline and Study Day ..........................................................................................13 
109 
4.2 
Determination of Sample Size ....................................................................................13 
110 
4.3 
Disposition of Subjects ...............................................................................................15 
111 
4.4 
Data Sets Analysed .....................................................................................................15 
112 
4.5 
Protocol Deviations ....................................................................................................16 
113 
4.6 
Demographic and Other Baseline Characteristics ......................................................17 
114 
4.6.1 
Medical History ......................................................................................................18 
115 
4.7 
Prior/Concomitant Medications..................................................................................18 
116 
4.8 
Study Drug Exposure and Compliance ......................................................................19 
117 
4.9 
Efficacy Analysis........................................................................................................20 
118 
4.9.1 
Primary Estimand and Intercurrent Events .............................................................20 
119 
4.9.2 
Analysis of Efficacy Variables ...............................................................................20 
120 
4.9.2.1 
Primary Efficacy Analysis ...................................................................................24 
121 
4.9.2.2 
Secondary Efficacy Analysis ...............................................................................25 
122 
4.9.2.3 
Exploratory Efficacy Analysis ............................................................................29 
123 
4.9.3 
Statistical / Analytical Issues ..................................................................................29 
124 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
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5 
4.9.3.1 
Adjustments for Covariates .................................................................................29 
125 
4.9.3.2 
Handling of Dropouts or Missing Data ...............................................................30 
126 
4.9.3.3 
Interim Analyses (IA), Data Monitoring and Primary Results 
127 
Reporting .............................................................................................................31 
128 
4.9.3.4 
Multicenter Studies ..............................................................................................32 
129 
 
 
 
4.9.4 
Tabulation of Individual Response Data ................................................................32 
131 
4.9.5 
Drug Dose, Drug concentration, and Relationships to Response ...........................33 
132 
4.9.6 
By-Subject Displays ...............................................................................................33 
133 
4.10 
Safety Analysis ...........................................................................................................33 
134 
4.10.1 
Adverse Events .......................................................................................................33 
135 
4.10.2 
Clinical Laboratory Evaluation ...............................................................................35 
136 
4.10.3 
Vital Signs ...............................................................................................................36 
137 
4.10.4 
12-Lead Electrocardiogram (ECG) .........................................................................36 
138 
4.10.5 
Physical Examinations ............................................................................................37 
139 
4.10.6 
Performance Status .................................................................................................37 
140 
4.10.7 
Other Safety Parameters .........................................................................................37 
141 
4.11 
Sensitivity and Subgroup Analyses ............................................................................38 
142 
4.12 
COVID-19 Pandemic Impacted Subjects Assessment ...............................................40 
143 
4.13 
Changes from Planned Analyses in the Protocol .......................................................40 
144 
 
 
 
6 
PROGRAMMING CONSIDERATIONS..................................................................44 
146 
6.1 
Table, Listing, and Figure Format ..............................................................................44 
147 
6.1.1 
General ....................................................................................................................44 
148 
6.1.2 
Headers ...................................................................................................................44 
149 
6.1.3 
Display Titles ..........................................................................................................44 
150 
6.1.4 
Column Headers .....................................................................................................45 
151 
6.1.5 
Body of the Data Display ........................................................................................46 
152 
6.1.6 
Demographics and Baseline Characteristics ...........................................................47 
153 
6.1.7 
Footnotes .................................................................................................................47 
154 
6.2 
Data-Handling Rules ..................................................................................................48 
155 




Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
7 
List of Abbreviations 
171 
Abbreviations 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine transaminase 
AST 
Aspartate transaminase/serum glutamic oxaloacetic transaminase 
BSA 
Body surface area 
CMH 
Cochran-Mantel-Haenszel 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CFR 
Code of Federal Regulations 
eCRF 
Electronic case report form 
CS 
Clinically significant 
DLQI 
Dermatology Life Quality Index 
ECG 
Electrocardiogram 
ECI 
Event of clinical interest 
EoS 
End of study 
EoT 
End of treatment 
ET 
Early termination 
FDA 
Food & Drug Administration 
ICH 
International Conference on Harmonization 
ICSR 
Interim Clinical Study Report 
IGA 
Investigator Global Assessment 
ITT 
Intent-To-Treat 
LOCF 
last-observation-carried forward 
M-N 
Miettinen-Nurminen methodology 
MACE 
Major Adverse Cardiovascular Events 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple Imputation 
mIGA 
Modified Investigator’s Global Assessment 
mITT 
Modified Intent-To-Treat 
MMRM 
Mixed Model Repeated Measures 
NCS 
Not clinically significant 
NRI 
Non-responder imputation 
NRS 
Numeric Rating Scale 
OC 
Observed Cases 
PASI 
Psoriasis Area and Severity Index 
PGA 
Physician’s Global Assessment  
PGA-S 
Physician Global Assessment of Skin 
PN 
Preferred Name 
PP 
Per Protocol 
PSSI 
Psoriasis Scalp Severity Index 
PT 
Preferred term 
SAE 
Serious adverse event 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
8 
SAF 
Safety analysis set 
SD 
Standard deviation 
SOC 
System organ class 
TEAE 
Treatment-emergent adverse event 
uITT 
Uniform Intent-To-Treat 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
9 
1 
INTRODUCTION 
173 
This Statistical Analysis Plan (SAP) Amendment has been developed following the review of 
174 
Sun Pharmaceutical Industries Ltd Protocol TILD-18-20 (Version 01 Amendment 03, dated 
175 
17 Mar 2020), the corresponding case report form (CRF), SAP Version 2.0 (dated 
176 
09-June-2021).  
177 
This SAP describes the analysis sets and specific details for the statistical methods to be used 
178 
for the analysis and reporting of all efficacy and safety data collected during the conduct of 
179 
Protocol TILD-18-20 during the initial blinded treatment period to Week 16, double blinded 
180 
active treatment period from Week 16 through Week 52, and observational safety follow-up 
181 
from Week 52 to Week 72. This SAP reflects changes to the statistical considerations in the 
182 
protocol. When needed, this SAP supersedes the statistical considerations identified in 
183 
Protocol TILD-18-20 and its amendments (as applicable). Where considerations are 
184 
substantially different, they will be identified as such in this document. 
 
185 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This SAP is being written with consideration of the recommendations outlined in the 
195 
International Conference on Harmonisation of Technical Requirements for Registration of 
196 
Pharmaceuticals for Human Use (ICH) E9 Guideline entitled “Guidance for Industry: 
197 
Statistical Principles for Clinical Trials”, the E9 Addendum on Estimands and Sensitivity 
198 
Analysis in Clinical Trials (R1) revision, and the most recent ICH E3 Guideline entitled, 
199 
“Guidance for Industry: Structure and Content of Clinical Study Reports.” 
200 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
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10 
2 
STUDY OBJECTIVES 
201 
The objectives of this study are as follows:  
202 
2.1 
Primary Objective  
203 
The primary efficacy objective of this study is: 
204 
x To assess the efficacy of tildrakizumab in subjects with moderate to severe scalp 
205 
psoriasis, as measured by the proportion of subjects who achieve Investigator Global 
206 
Assessment (IGA) mod 2011 (scalp) response from baseline at week 16. Response is 
207 
defined as shown in Table 1 of Section 4.9.2 below.   
208 
The primary safety objective of this study is:   
209 
x To assess the safety and tolerability of tildrakizumab in subjects with moderate to 
210 
severe plaque psoriasis of the scalp over 52 weeks. 
211 
2.2 
Secondary Objectives 
212 
The key secondary objectives of this study are: 
213 
x To assess the efficacy of tildrakizumab in subjects with moderate to severe plaque 
214 
psoriasis of the scalp, as measured by the proportion of subjects who achieve at least 
215 
90% improvement from Baseline in the Psoriasis Scalp Severity Index (PSSI) 
216 
response at Week 16 compared with placebo. 
217 
x To assess the efficacy of tildrakizumab in subjects with moderate to severe scalp 
218 
psoriasis, as measured by the proportion of subjects who achieve IGA mod 2011 
219 
(scalp) score of “clear” and “almost clear” with at least 2-point reduction from 
220 
Baseline at Week 12 
 
221 
 
 
 
 
x To assess the efficacy of tildrakizumab in subjects with moderate to severe plaque 
224 
psoriasis of the scalp, as measured by the proportion of subjects who achieve at least 
225 
90% improvement from Baseline in the PSSI response at Week 12 compared with 
226 
placebo. 
227 
 
228 
 
 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
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11 
x To assess the efficacy of tildrakizumab in subjects with moderate to severe scalp 
230 
psoriasis, as measured by the proportion of subjects who achieve IGA (scalp only) of 
231 
“clear” and “almost clear” with at least 2-point reduction from Baseline at Week 16. 
232 
x To assess the efficacy of tildrakizumab in the treatment of moderate to severe plaque 
233 
psoriasis of the scalp compared with placebo as measured by scalp surface area (SSA) 
234 
involvement at Week 16.  
235 
x To assess the effect of tildrakizumab on IGA mod 2011 (scalp) and PSSI at other 
236 
measured time points through week 52. 
237 
x To assess the effect of tildrakizumab on IGA (scalp only), Scalp Itch NRS, PASI, 
238 
PGA-S (whole body), and IGA mod 2011 (whole body), at week 12 and other 
239 
measured time points through Week 52. 
240 
x To assess the time to response  
241 
x To assess the efficacy of tildrakizumab in the improvement of scalp itch as measured 
242 
by the proportion of subjects achieving a 4-point reduction in Scalp Itch Numeric 
243 
Rating Scale (NRS) score from Baseline at Week 16 compared with placebo 
244 
x To assess the efficacy of tildrakizumab in the treatment of moderate to severe 
245 
psoriasis (entire body including scalp) compared with placebo as measured by 
246 
Psoriasis Area and Severity Index (PASI), IGA mod 2011 (whole body), Physician 
247 
Global Assessment for skin (PGA-S) score (whole body), and total body surface area 
248 
(BSA) involvement at Week 16. 
249 
2.3 
Exploratory Objective 
250 
The exploratory objective of this study is: 
251 
x To assess the effect of tildrakizumab on Quality of Life measured by: Dermatology 
252 
Life Quality Index (DLQI).  
253 
3 
OVERALL STUDY DESIGN AND TREATMENT PLAN 
254 
The overall study design and treatment plan are described in Sections 4.1 of Clinical Protocol 
255 
TILD-18-20 
. A brief overview is included below. 
256 
This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study to assess 
257 
the efficacy and safety of tildrakizumab in the treatment of moderate to severe psoriasis of 
258 
the scalp. The study will enroll approximately 214 subjects with moderate to severe psoriasis 
259 




Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
13 
4 
STATISTICAL CONSIDERATIONS OF PROTOCOL 
292 
4.1 
General Statistical Consideration 
293 
All summaries and analyses conducted will be by assigned therapy and/or combined total 
294 
subjects. Data obtained on the eCRF and entered into the database will be provided in data 
295 
listings showing individual subject values.   
296 
Descriptive statistics (number [n], mean, standard deviation [SD], median, first quartile [Q1], 
297 
third quartile [Q3], minimum [min], and maximum [max]) for continuous variables and 
298 
frequency distributions and percentages for discrete variables will be utilized. Categorical 
299 
variables will be summarized by frequencies and percentages.  
300 
 
301 
 
 
 
 
 
 
All tabulations of summary statistics, graphical presentations, and statistical analyses will be 
306 
performed using SAS® Version 9.4 or higher. 
307 
4.1.1 
Baseline and Study Day 
308 
For purpose of the SAP, Day 1 is defined as the date of first administration of study drug. 
309 
Study day is calculated relative to the date of Day 1. 
310 
Unless otherwise specified, “Baseline” is defined as the last observed value of the parameter 
311 
of interest prior to the first intake of study treatment (this includes unscheduled visits). For 
312 
numerical variables, change from Baseline will be calculated as the difference between the 
313 
post-Baseline value and the corresponding Baseline value. Change from Baseline is defined 
314 
as: post-Baseline value – Baseline value. The percent change from Baseline will be calculated 
315 
as change from Baseline divided by the Baseline value, expressed as a percentage.  
316 
4.2 
Determination of Sample Size 
317 
The study will randomize approximately 107 subjects per treatment arm (Total N=214) 
 
318 
 randomization to either tildrakizumab 100 mg arm (Arm A) or placebo arm (Arm B), 
319 
 
 
 
 
 
 
 
 
 






Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
16 
Safety Analysis Set (SAF): All randomized subjects who have received 
 dose of 
389 
study treatment.  
390 
Per Protocol Set (PP): All subjects 
 who have completed the 
391 
 placebo-controlled treatment without any major protocol deviation that could impact 
 
data interpretability for the primary efficacy endpoint. 
 
393 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Safety endpoints will be analyzed descriptively based on the SAF, and subjects will be 
409 
summarized based on the actual treatment they received.  
410 
4.5 
Protocol Deviations 
411 
All protocol deviations (PD) will be tracked throughout the study and classified by deviation 
412 
type, either minor or major. Protocol deviations represent a failure to adhere to the clinical 
413 
study protocol. The two types of deviations are defined as: 
414 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
17 
x Minor protocol deviation is any change, divergence, or departure from the study 
415 
design or procedures of a research protocol that has not been approved by the IRB and 
416 
which does not have a major impact on the subject's rights, safety or well-being, or 
417 
the completeness, accuracy and reliability of the study data. 
418 
x Major protocol deviation is any change, divergence, or departure from the study 
419 
design or procedures of a research protocol that has not been approved by the IRB and 
420 
which has a major impact on the subject's rights, safety or well-being, or the 
421 
completeness, accuracy and reliability of the study data. 
  
422 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
Prior to interim database freeze and final database lock, each deviation will be reviewed to 
430 
determine if it excludes the patient from any of the analysis sets or any particular planned 
431 
analysis. These determinations will then be described in the relevant clinical study report. 
432 
  
433 
Minor protocol deviations will be presented as well.  All deviations will be retained within 
434 
the deviations tracker (considered the source document). 
435 
Protocol deviations attributable to the COVID-19 pandemic regardless whether deemed 
436 
major or minor will be provided in a separate listing if deemed necessary.  Protocol 
437 
deviations will be presented in summary tables, for IA and overall, respectively.  
438 
4.6 
Demographic and Other Baseline Characteristics 
439 
Demographic and baseline characteristics generally will be summarized descriptively overall 
440 
and by treatment in the ITT, mITT, uITT, SAF, and PP analysis sets. The following 
441 
demographic and Baseline variables will be included: 
442 
x Age (years) 
443 
x Gender  
444 
x Race 
445 


Statistical Analysis Plan 
 
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Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
18 
x Ethnicity 
446 
x Prior use of TNF-alpha inhibitors (Yes/No) 
447 
x Weight (kg) 
448 
x Weight category (≤90 kg or >90 kg) 
449 
x Height (cm) 
450 
x BMI (kg/m2) 
451 
x Baseline IGA mod 2011 (scalp) 
 
452 
 
 
 
 
x Baseline IGA (scalp only) 
455 
x Baseline PSSI 
456 
x Baseline SSA involvement  
457 
x Baseline total BSA involvement  
458 
x Baseline IGA mod 2011 (whole body) 
 
459 
x Baseline PGA-S score (whole body) 
460 
x Baseline Scalp itch NRS score 
461 
x Baseline PASI score 
462 
All demographic data and baseline disease characteristics data will be listed by subject. 
463 
4.6.1 
Medical History 
464 
Medical/surgical history and concurrent procedures will be coded using the MedDRA 
465 
(Medical Dictionary for Regulatory Activities) Version 24.0 or a more recent version and will 
466 
be presented in a by-subject listing. 
467 
4.7 
Prior/Concomitant Medications 
468 
Prior and concomitant medications will be coded using the World Health Organization 
469 
(WHO) Drug Dictionary September 1, 2019 B3 Global. Prior medications include 
470 
medications used to treat the disease conditions and any other medications taken within 6 
471 
months prior to enrollment and stopped prior to start of treatment. Concomitant medications 
472 
during the study are defined as any medications that are ongoing or with stop dates on or after 
473 
date of first study medication administration. 
474 
For the determination of prior vs. concomitant medications, the following rules regarding the 
475 
stop date will be applied:  
476 
x If the stop date is missing completely, the medication is assumed to be a concomitant 
477 
medication. 
478 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
19 
x If only year was recorded, and it is before Baseline, it is a prior medication; if year is 
479 
same or after Baseline, it is assumed to be a concomitant medication.  
480 
x If day is missing, but month and year are before Baseline, it is a prior medication; if 
481 
month and year are the same as Baseline, it is assumed to be a concomitant medication; 
482 
if month and year are after Baseline, it is a concomitant medication.  
483 
x If start date is after Baseline, it is a concomitant medication regardless.  
484 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The number and percentage of subjects taking prior medications or concomitant medications 
491 
(overall and by study parts) will be summarized by anatomical therapeutic chemical (ATC) 
492 
level 3 and preferred name (PN) for the SAF. Although a subject may have taken two or more 
493 
medications, the subject is counted only once within an ATC classification. The same subject 
494 
may contribute to two or more PTs in the same classification. All prior and concomitant 
495 
medications will be listed by subject. 
496 
4.8 
Study Drug Exposure and Compliance 
497 
Study drug exposure will be evaluated using total number of doses administered for the entire 
498 
treatment period, and for Part 1 
at interim analysis and later, Part 2 
 
499 
separately for final analysis. Number and percent of doses 
 
administered per subject and number of subjects with dose administered at each scheduled 
501 
visit will be summarized with descriptive statistics by treatment arm (Part 1 only) and in total 
502 
using the Safety Analysis Set.  
503 
 
 
 
 
 
 
 
The study medication was originally designed to be administered at the study center by 
508 
trained staff; however, due to the outbreak of the COVID-19 pandemic, eligible and trained 
509 
subjects could self-administer study medication during modified remote study visits. 
510 
Self-administered study doses will be indicated in a listing.   
511 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
20 
All study drug administration data will be listed by subject.  
512 
4.9 
Efficacy Analysis 
513 
4.9.1 
Primary Estimand and Intercurrent Events 
514 
The primary estimand for this study is based on composite strategy approach.
 
515 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
4.9.2 
Analysis of Efficacy Variables 
529 
Efficacy endpoints will be summarized descriptively by randomized treatment and by visit 
530 
for subjects within ITT, mITT, and uITT Sets as per the specifications below. The mITT will 
531 
be considered as the primary population for primary efficacy analysis and the uITT and PP 
532 
Sets as supportive; the ITT will be considered as the primary population for key secondary 
533 
and all other efficacy endpoint analysis. The mITT and uITT Sets will be considered as the 
534 
sensitivity analysis populations for primary efficacy analyses. Subgroup analyses 
535 
incorporating multiple definitions of response may also be performed if sufficient subjects are 
536 
identified to contribute to such analyses.  
. 
537 
 
 
  
 
  
 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
21 
 
 
 
 
  
 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
CONFIDENTIAL 
 
22 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
CONFIDENTIAL 
 
23 










Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
28 
x PASI 90 at Week 16 
656 
x PASI 100 at Week 16 
657 
x PGA-S response at Week 16 
658 
Continuous endpoints 
659 
The following continuous endpoints will be analyzed based on the ITT population using a 
660 
mixed model for repeated measures (MMRM) procedure
661 
 
 
 
 
 
 
 
x Mean percentage change in PSSI score from Baseline to Week 16 
666 
x Mean percentage change in SSA involvement from Baseline to Week 16 
667 
x Mean percentage change in total BSA involvement from Baseline to Week 16 
668 
Treatment difference between tildrakizumab arm and placebo arm will be reported,
 
669 
  
 
Time to treatment response: 
671 
Time to IGA mod 2011 (scalp) response and time to PSSI-75 will be analyzed using the 
672 
Kaplan-Meier method 
 
673 
 
 
 
 
Other endpoints: 
677 
Change from Baseline for the following endpoints at measured time points 
 
678 
will be summarized in the mITT, 
 
 
or ITT population as appropriate, using descriptive statistics:  
680 
x IGA mod 2011 (scalp)  
681 
x PSSI 
682 
x IGA (scalp only) 
683 
x Scalp Itch NRS 
684 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
29 
x PASI 
685 
x PGA-S (whole body) 
686 
x IGA mod 2011 (whole body) 
687 
x SSA involvement  
688 
x BSA involvement 
689 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
4.9.2.3 
Exploratory Efficacy Analysis 
699 
Exploratory efficacy endpoints include change from Baseline at measured time points through 
700 
Week 52 
 for DLQI score (total and 6 
701 
domain scores). 
702 
 
 
.  
 
Exploratory efficacy endpoints also include subjects achieving IGA mod 2011 (scalp) 
704 
response and PSSI 90 response
 
705 
 
The exploratory efficacy endpoint of the proportion of IGA mod 2011 (scalp) and PSSI 90 
707 
maintained response includes subjects with a response at Week 16 and maintained the 
708 
response through Week 52. 
709 
All efficacy endpoints will be summarized for the ITT or mITT population using descriptive 
710 
statistics for all scheduled visits, for each randomized treatment arm and overall. 
711 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
30 
4.9.3 
Statistical / Analytical Issues 
712 
 
 
 
 
 
 
 
4.9.3.2 
Handling of Dropouts or Missing Data 
717 
Data from subjects who withdraw from the study, including AEs and any follow-up, will be 
718 
included in the analyses as applicable.  
719 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
31 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
4.9.3.3 
Interim Analyses (IA), Data Monitoring and Primary Results Reporting 
763 
Following the last subject’s Week 16 visit, the IA (primary analysis) will be conducted on 
764 
available data to evaluate efficacy and safety.   
765 
  
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
32 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
4.9.3.4 
Multicenter Studies 
795 
Descriptive summaries of the primary and key secondary efficacy endpoints will be presented 
796 
for each individual study center to evaluate potential heterogeneity across sites. 
797 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
33 
 
 
 
 
 
 
4.9.4 
Tabulation of Individual Response Data 
810 
All efficacy variables will be listed by subject.  
811 
4.9.5 
Drug Dose, Drug concentration, and Relationships to Response 
812 
 Not applicable.  
813 
4.9.6 
By-Subject Displays 
814 
No individual subject profile data will be produced.  
815 
 
 
 
 
 
   
 
4.10 Safety Analysis 
820 
The safety and tolerability of the study drugs will be evaluated by reported adverse events 
821 
(AEs), physical examinations, electrocardiogram results (ECGs), vital signs, laboratory test 
822 
results (Hematology, Biochemistry, and Urinalysis), and Columbia-Suicide Severity Rating 
823 
Scale (C-SSRS).  
824 
All safety summaries will be based on the Safety Analysis Set. 
825 
Following reporting of interim Week 16 results, a group comprising formerly placebo-treated 
826 
subjects who migrate to tildrakizumab 100 mg for the remainder of the study will be 
827 
identified for reporting at the end of the study. 
828 
4.10.1 
Adverse Events 
829 
The incidence of treatment-emergent AEs (TEAE) will be summarized and tabulated by 
830 
treatment group, MedDRA (Version 24.0 or higher) System Organ Class (SOC) and 
831 
Preferred Term (PT). A TEAE is defined as an AE that first occurred or worsened in severity 
832 
after the first administration of study treatment.  
833 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
34 
Several occurrences of the same AE in one subject will be counted once at the worst severity 
834 
grade.
 
835 
 
The relationship of each AE to the study drug will be grouped as related (definitely, probably, 
837 
possibly related) or unrelated (unlikely to be related, unrelated). Several occurrences of the 
838 
same AE in one subject will be counted once and the one with the closest relationship to 
839 
study medication will be counted. If an AE is missing the relationship to study medication, 
840 
the event will be assumed to be related to study drug for analysis and summarization. 
841 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Non-TEAEs will be listed only and will not be included for analysis and summarization.  
848 
All AEs will be presented in a by-treatment and by-subject listing, detailing the verbatim 
849 
term, SOC, PT, application site reaction or not, related to study indication or not, start date, 
850 
stop date, time since most recent dose of IP, severity, outcome, relationship to study drug, 
851 
action taken regarding study drug, action taken to treat AE, seriousness and criteria for 
852 
seriousness. Serious AEs (SAEs) and TEAEs leading to study medication discontinuation, 
853 
AEs of Special Interest (AESI), and events of clinical interest (ECI) will also be presented in 
854 
separate listings.  
855 
An AE profile for the Safety Analysis Set will be provided for Part 1, Parts 2 and 3, and 
856 
overall, which summarizes the subject incidence, by treatment received for the following 
857 
information: 
858 
x Any TEAEs; 
859 
x Non-TEAEs; 
860 
x Drug-related TEAEs; 
861 
x Any TEAEs with an outcome of death; 
862 
x Treatment-emergent SAEs; 
863 
x Drug-related treatment-emergent SAEs; 
864 
x TEAEs leading to discontinuation of study medication;  
865 
x Drug-related TEAEs leading to discontinuation of study medication; 
866 




Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
36 
COVID-19 related adverse events may also be summarized separately if deemed necessary. 
903 
4.10.2 
Clinical Laboratory Evaluation 
904 
Absolute values and changes from Baseline of clinical laboratory data (hematology, 
905 
chemistry, continuous urinalysis parameter and lipids) will be summarized with descriptive 
906 
statistics at Baseline, and Week 16 
 at the interim 
 
907 
 
 
 
 
  
 
All clinical laboratory data relevant to the reporting period 
 will be 
912 
listed by subject. Values outside the normal ranges will be flagged. Flags will describe 
913 
direction relative to normal range in relevant parameters. 
914 
4.10.3 
Vital Signs 
915 
Vital signs measurements including temperature, pulse rate, systolic blood pressure, and 
916 
diastolic blood pressure, respiratory rate at each scheduled visit and changes from baseline 
917 
during the treatment period will be summarized by treatment arm. Vital signs will also be 
918 
presented in a shift table displaying the cross tabulation of the Baseline result category versus 
919 
the result of the post-treatment period at each scheduled visit. The categories of each vital 
920 
sign parameters are as below: 
921 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
37 
4.10.4 
12-Lead Electrocardiogram (ECG) 
923 
The ECG measurements at each scheduled visit 
 
924 
 and change from baseline 
 
during the treatment period will be summarized by treatment arm.  
926 
All ECG measurements and the overall interpretation will be listed by subject
927 
 
 
 
 
4.10.5 
Physical Examinations 
930 
The frequency of subjects with abnormal evaluations of body system findings for physical 
931 
examinations will be summarized by visit and treatment group; abnormal physical 
932 
examination findings will also be presented in a by-subject listing. 
933 
4.10.6 
Performance Status 
934 
Not applicable. 
935 
4.10.7 
Other Safety Parameters  
936 
The subjects will be assessed for suicidal ideation and behavior using Columbia-Suicide 
937 
Severity Rating Scale (C-SSRS) at screening, baseline and each subsequent visit. C-SSRS 
938 
contains two categories: (1) Suicidal Ideation (questions 1-5), most severe ideation will also be 
939 
collected; (2) Suicidal behavior (questions 6-10).  
940 
The following outcomes are C-SSRS categories and have binary responses (yes/no).  The 
941 
categories listed below have been re-ordered from the actual scale in an increasing order of 
942 
severity from 1 to 10 to facilitate the definitions of the comparative endpoints.  
943 
Table 2 C-SSRS Outcomes 
944 
Categories 
Suicidal Ideation (1-5) 
1 – Wish to be dead 
2 – Non-specific active suicidal thoughts 
3 – Active suicidal ideation with any methods (not plan) without intent to act 
4 – Active suicidal ideation with some intent to act, without specific plan 
5 – Active suicidal ideation with specific plan and intent 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
38 
Categories 
Suicidal behavior (6-10) 
6 – Preparatory acts or behavior 
7 – Aborted attempt 
8 – Interrupted attempt 
Suicidal acts (9-10) 
9 – Non-fatal suicide attempt 
10 – Completed suicide 
The following are numerical scores derived from the above C-SSRS categories.  
945 
x Suicidal Ideation Score: The maximum suicidal ideation category (1-5 on the C-SSRS) 
946 
present at the assessment. Assign a score of 0 if no ideation is present. 
947 
x Suicidal Behavior Score: The maximum suicidal behavior category (6-10 on the 
948 
C-SSRS) present at the assessment. Assign a score of 0 if no behavior is present. 
949 
x Suicidal Ideation or Behavior Score: The maximum suicidal ideation or behavior 
950 
category (1-10 on the C-SSRS) present at the assessment. Assign a score of 0 if no 
951 
ideation or behavior is present. 
952 
Subjects are also classified into two risk levels: 
953 
x Intermediate risk level is indicated by a response of “yes” to Questions 1 to 3 and the 
954 
absence of a “yes” response to Questions 4 and 5. 
955 
x High risk level is indicated by a response of “yes” to Questions 4 or 5 in the suicidal 
956 
ideation section, or any positive response in the behavioral section of the C-SSRS. 
957 
Change in binary response to the questions from no to yes in any questions will be summarized 
958 
in a shift table describing baseline vs post-baseline per visit, and worst post-baseline overall. 
959 
Categorical scores will be analyzed similarly. C-SSRS risk levels are also summarized by visit. 
960 
Results from the C-SSRS will be listed by subject.  Results to Week 16 will be described in the 
961 
Part 1 interim analysis, and overall results to Week 52 and 72 will be described in the final 
962 
analysis. 
963 
4.11 Sensitivity and Subgroup Analyses 
964 
Sensitivity and subgroup analyses will be performed to confirm the robustness of primary 
965 
analysis results.  
966 
  
 
.  
 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
39 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
40 
common risk difference and the associated 
 
991 
 
 
 
 
 
 
 
 
 
Tipping point analysis 
997 
A tipping point analysis under a missing not at random (MNAR) assumption will be 
998 
performed as a sensitivity analysis to assess assumptions about any missing outcomes on 
999 
the two treatment arms. 
 
1000 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
4.12 COVID-19 Pandemic Impacted Subjects Assessment 
1021 
COVID-19 impacted subjects will be identified from study tracking documentation and event-
1022 
level impacts will be integrated to the EDC. Events that exceed 5% subject-level incidence of 
1023 




Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
42 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
Sensitivity analyses are revised to include only primary and key secondary endpoints, 
1073 
since other secondary efficacy endpoints are less meaningful to the objectives of the 
1074 
study. 
1075 
Section 4.11 defines examinations of subgroups and sensitivity analyses. 
1076 
Multiple sections identify removal of sensitivity analyses related to secondary 
1077 
endpoints. Section 3 defines dose-relative criteria for completion of Part 1 and 
1078 
initiation of Parts 2 and 3 of the protocol. 
1079 
Handling of COVID-19 pandemic-related events are specified in the SAP in the 
1080 
sections shown below: 
1081 
o 4.3 
Disposition of Subjects, 
1082 
o 4.5 
Protocol Deviations, 
1083 
o 4.8 
Study Drug Exposure and Compliance, 
1084 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
43 
o 4.9.1 Primary Estimand and Intercurrent Events, 
1085 
o 4.12 
COVID-19 Pandemic Impacted Subject Assessments 
1086 
Section 4.9.6 describes by-subject displays  
1087 
Section 6.2.1 describes COVID-19 impacts to Visits  
1088 
Section 6.2.4 describes SAS® Procedures for M-N methodology implementation 
1089 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
44 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
45 
6 
PROGRAMMING CONSIDERATIONS 
1105 
All tables, data listings, figures (TLFs), and statistical analyses will be generated using SAS® 
1106 
Version 9.4 or above. Generated outputs will adhere to the following specifications. 
1107 
6.1 
Table, Listing, and Figure Format 
1108 
6.1.1 
General 
1109 
1) All TLFs will be produced in landscape format. 
1110 
2) All TLFs will be produced using the Courier New font, size 8. 
1111 
3) The data displays for all TLFs will have a 1.5-inch binding margin on top of a 
1112 
landscape oriented page and a minimum 1-inch margin on the other 3 sides. 
1113 
4) Headers and footers for figures will be in Courier New font, size 8. 
1114 
5) Legends will be used for all figures with more than 1 variable, group, or item 
1115 
displayed. 
1116 
6) TLFs will be in black and white (no color). 
1117 
7) Specialized text styles, such as bolding, italics, borders, shading, and superscripted 
1118 
and subscripted text, will not be used in the TLFs. On some occasions, superscripts 1, 
1119 
2, or 3 may be used (see below). 
1120 
8) Only standard keyboard characters will be used in the TLFs. Special characters, such 
1121 
as non-printable control characters, printer-specific, or font-specific characters, will 
1122 
not be used. Hexadecimal-derived characters will be used, where possible, if they are 
1123 
appropriate to help display math symbols (e.g., μ). Certain superscripts (e.g., cm2) will 
1124 
be employed on a case-by-case basis. 
1125 
9) Mixed case will be used for all titles, footnotes, column headers, and programmer-
1126 
supplied formats. 
1127 
6.1.2 
Headers 
1128 
1) All output should have the following header at the top of the page: 
1129 
Sun Pharmaceutical Industries Ltd     Status – Draft/Final      Page  n of N  
1130 
Study: TILD-18-20                                   Interim/Final Analysis 
1131 
All output should have page number. TLFs should be internally paginated in relation to the 
1132 
total length (i.e., the page number should appear sequentially as page n of N, where N is the 
1133 
total number of pages in the table, listing or figure). 
1134 
6.1.3 
Display Titles 
1135 
Each TLF should be identified by a numeral, and the designation (i.e.,  
1136 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
46 
1) Table 1) should be centered above the title. A decimal system (Table 14.x.y.z, Figure 
1137 
14.x.y.z, and Listing 16.2.x.y) should be used to identify TLFs with related contents. 
1138 
The title is centered in initial capital characters. The analysis set should be identified 
1139 
on the line immediately following the title. The title and table designation are single 
1140 
spaced. A solid line spanning the margins will separate the display titles from the 
1141 
column headers. There will be 1 blank line between the last title and the solid line. 
1142 
Table 14.x.y.z 
1143 
First Line of Title 
1144 
Second Line of Title if Needed 
1145 
FAS 
1146 
6.1.4 
Column Headers 
1147 
1) Column headings should be displayed immediately below the solid line described 
1148 
above in initial upper-case characters. 
1149 
2) For numeric variables, include “unit” in column or row heading when appropriate. 
1150 
3) Analysis set sizes will be presented for each treatment group in the column heading as 
1151 
(N=xx) (or in the row headings if applicable). This is distinct from the ‘n’ used for the 
1152 
descriptive statistics representing the number of subjects in the analysis set. 
1153 
4) The order of treatments in the tables and listings will be: Placebo and Tildrakizumab 
1154 
100 mg, and Total (if applicable). 
1155 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
47 
6.1.5 
Body of the Data Display 
1156 
1) Listings data will be sorted for presentation in order of treatment groups as above, 
1157 
subject ID, collection day, and collection time. 
1158 
2) If the categories of a parameter are ordered, then all categories between the maximum 
1159 
and minimum category should be presented in the table, even if n=0 for all treatment 
1160 
groups in a given category that is between the minimum and maximum level for that 
1161 
parameter. For example, the frequency distribution for symptom severity would 
1162 
appear as: 
1163 
Severity Rating 
n 
severe 
0 
moderate 
8 
mild 
3 
Where percentages are presented in these tables, any counts of 0 will be presented as 
1164 
0 and not as 0 (0%). 
1165 
3) If the categories are not ordered (e.g., Medical History, Reasons for Discontinuation 
1166 
from the Study, etc.), then only those categories for which there is at least 1 subject 
1167 
represented in 1 or more groups should be included. 
1168 
4) An Unknown or Missing category for categorical summarization should be added to 
1169 
any parameter for which information is not available for 1 or more subjects. 
1170 
5) Unless otherwise specified, the estimated mean and median for a set of values should 
1171 
be printed out to 1 more significant digit than the original values, and standard 
1172 
deviations should be printed out to 2 more significant digits than the original values. 
1173 
The minimum and maximum should report the same significant digits as the original 
1174 
values. For example, for systolic blood pressure: 
1175 
n 
XX 
Mean 
XXX.X 
SD 
X.XX 
Median 
XXX.X 
Range 
(XXX, XXX) 
 
1176 
6) All p-values should be output in the format: “0.xxxxx”, where xxx is the value 
1177 
rounded to 5 decimal places. Any p-value less than 0.00001 will be presented as 
1178 
<0.00001. 
1179 
7) Data in columns of a table should be formatted as follows: 
1180 
• 
alphanumeric values are left-justified; 
1181 
• 
whole numbers (e.g., counts) are right-justified; and 
1182 
• 
numbers containing fractional portions are decimal aligned. 
1183 
8) Percentage values should be printed with 1 digit to the right of the decimal point in 
1184 
parentheses set 1 space after the count (e.g., 7 (12.8%), 13 (5.4%)). Less-than-signs 
1185 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
48 
“<0.1%” should be printed when values are >0.0% and <0.1% (not 0.0%). Unless 
1186 
otherwise noted, for all percentages, the number of subjects in the analysis set for the 
1187 
treatment group who have an observation will be the denominator. 
1188 
9) Tabular display of data for prior / concomitant medications, and all tabular displays of 
1189 
adverse event data should be presented by the body system, drug class, or SOC with 
1190 
the highest occurrence in the active treatment group in decreasing order. Within the 
1191 
body system, drug class and SOC, medical history (by PT), drugs (by ATC3 code), 
1192 
and adverse events (by PT) should be displayed in decreasing order. If incidence for 
1193 
more than 1 term is identical, they should then be sorted alphabetically. 
1194 
10) Missing data should be represented on subject listings as either a hyphen (“-”) with a 
1195 
corresponding footnote (“ - = unknown or not evaluated”), or as “N/A”, with the 
1196 
footnote “N/A = not applicable”, whichever is appropriate. For summary tables, 
1197 
missing descriptive statistics or p-values due to non-estimability should be reported as 
1198 
“-” with a corresponding footnote (“- = not estimable”).. 
1199 
11) Date should be printed in ISO date format (“yyyy-mm-dd”: 2000-07-01). Missing 
1200 
portions of dates should be represented on subject listings as partial dates (2000-07). 
1201 
Dates that are missing because they are not applicable for the subject are output as 
1202 
“N/A”, unless otherwise specified. 
1203 
12) All observed time values must be presented using a 24-hour clock HH:MM:SS format 
1204 
(e.g., 01:35:45, or 11:26). Time will only be reported if it was measured as part of the 
1205 
study. 
1206 
6.1.6 
Demographics and Baseline Characteristics 
1207 
1) Age = (Date of informed consent - Date of birth + 1) / 365.25 and truncated to 
1208 
complete years. 
1209 
2) Conversion factors and calculations for height, weight, and BMI: 
1210 
• 
Height (in cm) = height (in inches) * 2.54 
1211 
• 
Weight (in kg) = weight (in lbs) * 0.4536 
1212 
• 
BMI (kg/m2) = Weight(kg)/[Height(m)2] 
1213 
3) The value of XX (e.g. age or day of assessment) will be calculated relative to a 
1214 
reference time point X (e.g. time of enrollment/first dose). If reference day/month is 
1215 
missing, the first day of the month/year will be used to create a SAS® date for 
1216 
variables ‘Date of X ’. 
1217 
6.1.7 
Footnotes 
1218 
1) A solid line spanning the width between the left and right margins will separate the 
1219 
body of the data display from the footnotes.  
1220 
2) All footnotes will be left justified with single-line spacing immediately below the 
1221 
solid line underneath the data display. 
1222 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
49 
3) Footnotes should always begin with “Note:” if an informational footnote, or asterisks 
1223 
and other non-numeric symbols if an annotated footnote. Each new footnote starts on 
1224 
a new line. 
1225 
4) Footnotes will be present on the page where they are first referenced and thereafter on 
1226 
each page of the table, unless the footnote is specific only to certain pages. Subject 
1227 
specific footnotes should be avoided. 
1228 
5) Footnotes will be used sparingly and must add value to the table, figure, or data 
1229 
listing. If more than 4 footnotes are planned, then a cover page may be used to display 
1230 
footnotes, and only those essential to comprehension of the data will be repeated on 
1231 
each page. Footnotes should not repeat definitions already provided in the SAP. 
1232 
6) The last line of the footnote section will be a standard source line that indicates the 
1233 
data source called in by the program, the name of the program used to produce the 
1234 
data display, and the listing source (i.e., ‘Data source: xyzabc.sas7bdat    Program 
1235 
source: myprogram.sas    Listing source: 16.x.y.z’). 
1236 
6.2 
Data-Handling Rules 
1237 
This section describes naming conventions and rules for calculations that would be common 
1238 
to all applicable tables. Some rules specific to a table can be found in the relevant mock-ups. 
1239 
6.2.1 
Visits 
1240 
1) Relative Study Day: The first day of treatment is Day 1. A minus (-) sign indicates 
1241 
days prior to the start of treatment (e.g., Day -5 represents 5 days before start of 
1242 
therapy. There is no Day 0. The relative study day for a specific post-baseline visit is 
1243 
calculated as (Visit Date - Date of First Dose +1). 
1244 
2) Baseline: Evaluation taken on baseline visit or the last available evaluation prior to 
1245 
the first dose of study drug if the former is missing. 
1246 
3) COVID-19 affected week 16 visit: by-subject listing will show imputed and modeled 
1247 
results. See Section 4.11 for additional details.  
1248 
6.2.2 
Prior and Concomitant Medications 
1249 
1) Prior and concomitant medications will be coded and classified using the treatment 
1250 
start and stop dates relative to date of first study medication. The specific dictionary 
1251 
version will be provided in the actual tables/listings. 
1252 
2) Counting rules for prior/concomitant medications: Prior medications refer to all 
1253 
medications that were taken within 6 months prior to enrollment and stopped prior to 
1254 
start of treatment. Concomitant medications refer to all medications that started at any 
1255 
time and were taken at any time after the start of treatment until the end of the entire 
1256 
treatment period including those continued from pre-treatment. 
1257 
3) Medications missing both start and stop dates, or having a start date prior to the last 
1258 
dose of study drug and missing the stop date, or having a stop date after the start of 
1259 


Statistical Analysis Plan 
 
Protocol TILD-18-20 
Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
50 
study drug and missing the start date, will be counted as concomitant. When partial 
1260 
dates are present in the data, both a partial start date and/or a partial stop date will be 
1261 
evaluated to determine whether it can be conclusively established that the medication 
1262 
either ended prior to the start of study drug or started after the end of study drug. If 
1263 
the above cannot be conclusively established based on the partial and/or present dates, 
1264 
then the medication will be counted as concomitant. 
1265 
6.2.3 
Safety 
1266 
1) If multiple results (e.g., lab test results) are reported at a study visit, then the last 
1267 
available result reported for that visit will be used in that visit summary. 
1268 
2) Adverse events will be coded and classified using MedDRA. The specific dictionary 
1269 
version will be provided in the actual tables/listings. 
1270 
3) Counting rules for AEs: AEs with missing start dates, but with stop dates either 
1271 
overlapping into the treatment period or missing, will be counted as treatment-
1272 
emergent, taking the worst-case approach. Special care will be taken regarding partial 
1273 
dates with similar logic to that of the prior/concomitant medications applied. 
1274 
4) For purposes of flagging individual subject data, laboratory test result abnormalities 
1275 
are defined as values above or below the normal range. 
1276 
5) Conversion factor for temperature: 
1277 
Temperature (in °C) = 5/9 (Temperature [in °F]-32). 
1278 
Conversion factors for ECG QT to QTcF if any subjects do not have reported QTcF 
1279 
values but have reported QT and RR values: 
1280 
Fridericia formula: QTcF = QT / (RR 1/3) 
1281 
6.2.4 
SAS® Procedures 
1282 
This section provides sample SAS® code to illustrate statistical tests specified in the statistical 
1283 
methods section. All computer output from SAS® statistical procedures serving as a basis for 
1284 
extracted results (e.g., MIXED, FREQ/CMH) will be retained for quality control procedures 
1285 
and will be included in CSR appendices. 
1286 
1) The percentage change from baseline is calculated as the post-baseline score minus 
1287 
the baseline score, and the difference divided by the baseline score, expressed in units 
1288 
of percent. The mean percentage change is derived as the least squares mean for 
1289 
treatment/visit interaction from the mixed model shown in 4) below.   
1290 
2) M-N  Method:  
1291 
The M-N  method will be used for the primary efficacy analysis, which provides 
1292 
point estimates for the difference between treatments, and their corresponding 
1293 
  
1294 
  
 






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Statistical Analysis Plan 
 
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Sun Pharmaceutical Industries Ltd 
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30-Mar-2022 
 
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IA 


Statistical Analysis Plan 
 
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Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
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Statistical Analysis Plan 
 
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Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
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58 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 


Statistical Analysis Plan 
 
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Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
CONFIDENTIAL 
 
59 
  
  
 
  
 
  
 
  
 
  
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
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Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
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Statistical Analysis Plan 
 
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Sun Pharmaceutical Industries Ltd 
30-Mar-2022 
 
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62 
APPENDIX 1  
PASI SCORING 
1340 
PASI is evaluated within each of the four body regions: a) head, b) upper limbs, c) trunk, and 
1341 
d) lower limbs;  
1342 
 
 
1343