A Long-Term Extension Study to Demonstrate Safety of Tildrakizumab in Subjects With Psoriatic Arthritis Who Have Previously Completed Study With Tildrakizumab.
Phase: PHASE2
Conditions: Psoriatic Arthritis
Sponsor: Sun Pharmaceutical Industries Limited

Official title: A Long‐Term extension study to demonstrate safety of Tildrakizumab in subjects with 
Psoriatic Arthritis who have previously completed study with Tildrakizumab.    
Document: Clinical Study Protocol 
NCT number: NCT03552276 
Document date: 22‐Jul‐2020 

 
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Protocol CLR_18_07 
Amendment 1.0 (Final)  
 
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Name of Sponsor/Company: 
Sun Pharma Global FZE 
Individual Study 
Table Referring to Part of the 
Dossier: 
 
 
Volume: 
 
Page: 
(For National Authority Use Only) 
Name of Product: 
Tildrakizumab 
Name of Active Ingredient: 
Tildrakizumab 
The study will consist of a Baseline visit (Week 0) which will be the same as Week 52 of the parent study 
12-weekly visits (from Week 8) up to approximately 2 years from the start of the extension study, followed by 
24-weekly visits thereafter (from Week 104) up until approximately 4 years after the start of the study 
(approximately 5 years from the start of the parent study).   
The parent Phase 2 study will retain a blind status at the time of the initiation of the extension study 
(double-blind for the PsA study, i.e., only the Sponsor and designated contract research organization [CRO] 
team members not directly related to the clinical conduct of the study will have been unblinded).  Safety 
assessments will be conducted at the 12 weekly or 24-weekly visits in accordance with the Schedule of 
Assessments.  
All scheduled visits will occur at the study site.  However, should unusual circumstances such as public health 
emergency (i.e. pandemic with an infectious agent) or natural disasters arise, video conference or 
teleconference between the subject and site investigator will be permitted as deemed appropriate by the Sponsor 
provided no physical examination is needed for the visit.  In this unusual circumstance, self-injection  made by 
the subject at subject’s home is allowed in order to guarantee treatment continuity. 
When all subjects have completed the PsA parent Phase 2 study, the blind will no longer need to be maintained 
for the cohort, and this long-term extension study will have the option to become   open-label for those subjects.  
Note: the timing of switch to an open-label design may differ across the cohorts of subjects entered, depending 
on the parent study.  If other studies are also included in the long-term extension study, similar considerations 
for maintenance of blind will be necessary.  Those subjects will be entered as separate cohorts and procedures 
such as continued double-dummy dosing regimens will be utilized, even after other parent Phase 2 cohorts 
have the option to switch to open-label. 
Subjects not deriving sufficient clinical benefit in the opinion of the Investigator at any time after the initiation 
of this long-term extension study should be discontinued from investigational medicinal product (IMP), and 
receive clinical care as determined by the Investigator. 
With the exception of those who withdraw informed consent, subjects who withdraw from IMP during the 
long-term extension study will undergo the EoT assessments approximately 4 weeks after their last 
administration of IMP.  Subjects who complete treatment to Week 200 will return for a Follow-up assessment 
at Week 208 (4 years). 
No independent assessor is needed to assess efficacy measurements.  There will be no efficacy assessments 
during the LTE study. The Principal Investigator (PI)/designee will be responsible for performing safety 
evaluations. 
Clinical Adjudication Committee will be established to evaluate cardiovascular events. 
End of study is defined as the last visit of the 4-year treatment period (Week 208, EoT/Follow-up) for the last 
global subject. 

 
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Amendment 1.0 (Final)  
 
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Name of Sponsor/Company: 
Sun Pharma Global FZE 
Individual Study 
Table Referring to Part of the 
Dossier: 
 
 
Volume: 
 
Page: 
(For National Authority Use Only) 
Name of Product: 
Tildrakizumab 
Name of Active Ingredient: 
Tildrakizumab 
Number of Subjects: 
Up to 286 subjects with PsA could be enrolled from the parent Phase 2 study.  
Diagnosis and Main Criteria for Inclusion: 
Inclusion Criteria: 
Subjects may be included in the study if they meet all of the following criteria: 
1. Subject has provided written informed consent for this long-term extension study. 
2. Subjects with PsA who met the inclusion criteria of the parent study and completed the parent study 
treatment period (e.g., up to Week 48 for the parent Phase 2 study, with return for the EoT assessment at 
Week 52). 
3. PsA subjects who achieved a 20% reduction from Baseline in American College of Rheumatology 
(ACR)20 response criteria at Week 52, AND the subject has received sufficient clinical benefit, in the 
opinion of the Investigator, to support continued treatment with tildrakizumab. 
This criterion using response criteria at Week 52 will apply to all subjects, including those subjects who 
enter the study from the wash-out phase of their parent study (after Week 52) due to the timing of study 
site activation of the long-term extension study.   
4. No concomitant use of both leflunomide and methotrexate simultaneously. 
5. No history of active tuberculosis (TB) or symptoms of TB. 
Exclusion Criteria: 
Subjects should be excluded from the study if they meet any of the following criteria: 
1. New onset during the parent study of arthritic conditions other than the subject's original condition. 
2. Female subjects of childbearing potential who do not agree to abstain from heterosexual activity or practice 
a dual method of contraception, for example, a combination of the following: (1) oral contraceptive, 
depo-progesterone, or intrauterine device; and (2) a barrier method (condom or diaphragm).  Male subjects 
with female partners of childbearing potential who are not using birth control as described above must use 
a barrier method of contraception (e.g., condom) if not surgically sterile (i.e., vasectomy).  Contraceptive 
methods must be practiced upon entering the study and through 16 weeks after the last dose of IMP.  If a 
subject discontinues prematurely, the contraceptive method must be practiced for 16 weeks following final 
administration of IMP. 
3. Female is pregnant or breastfeeding, or planning to become pregnant or initiate breastfeeding while 
enrolled in the study or up to 16 weeks after the last dose of IMP. 
4. Subject has previously been enrolled in this long-term extension study. 
5. Any condition that in the opinion of the Investigator represents an obstacle for study conduct and/or 
represents a potential unacceptable risk for the subject. 
6. Subject has an active infection or history of infections as follows: 
− 
a serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks 
prior to the first IMP dose of the extension study, with the last dose having been received within 7 days 
of start of the extension study, 
− 
recurrent or chronic infections, e.g., chronic pyelonephritis, chronic osteomyelitis, bronchiectasis, or 
other active infection that, in the opinion of the Investigator, might cause this extension study to be 
detrimental to the subject. 

 
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Amendment 1.0 (Final)  
 
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Name of Sponsor/Company: 
Sun Pharma Global FZE 
Individual Study 
Table Referring to Part of the 
Dossier: 
 
 
Volume: 
 
Page: 
(For National Authority Use Only) 
Name of Product: 
Tildrakizumab 
Name of Active Ingredient: 
Tildrakizumab 
7. Major chronic inflammatory or connective tissue disease other than PsA (e.g., rheumatoid arthritis, 
systemic lupus erythematosus, Lyme disease, gout, Crohn’s disease, etc). 
8. Known diagnosis of fibromyalgia, regional pain syndromes or active uveitis/symptomatic inflammatory 
bowel disease requiring therapy. 
9. Subject has any concurrent medical condition or uncontrolled, clinically significant systemic disease (e.g., 
renal failure, heart failure, hypertension, liver disease, diabetes, or anemia) that, in the opinion of the 
Investigator, could cause continued treatment to be detrimental to the subject. 
10. Subject has a known history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus 
during the parent study. 
11. Subject had myocardial infarction, unstable angina pectoris, or ischemic stroke within the past 6 months 
prior to the first IMP dose for this extension study. 
12. Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or 
melanoma. 
13. Subject has a history of malignancy EXCEPT treated and considered cured cutaneous basal or squamous 
cell carcinoma, in situ cervical carcinoma, OR in situ breast ductal carcinoma. 
14. Subjects with a history of alcohol or drug abuse during the parent study. 
15. Significant risk of suicidality at the Baseline assessment of this extension study based on the Investigator's 
judgment or, if appropriate, as indicated by a response of "yes" since the last visit to question 4 or 5 in the 
suicidal section, or any response in the behavioral section of the C-SSRS. 
16. Subject has a need for use of a live vaccine within 10 weeks of final anticipated dose of IMP for the 
long-term extension study. 
17. Concomitant use of prohibited medications or use of commercially available or investigational biologic 
therapies (other than tildrakizumab) for psoriasis or PsA. 
General 
18. Subjects who have been placed in an institution on official or judicial orders. 
19. Subjects who are related to or dependent on the Investigator, Sponsor, or study site such that a conflict of 
interest may arise. 
Test Product, Dose and Mode of Administration: 
The IMP will be supplied as a 
 and administered subcutaneously (SC).  All subjects 
will be dosed at the same time points with 100 mg tildrakizumab Q12 weeks (one 1-mL injection of 
100 mg/mL) at Weeks 0, 8, 20, 32, 44, 56, etc and all subsequent 12-weekly time points to Week 200. 
Reference Therapy, Dose and Duration of Administration: 
There will be no placebo comparator in this study.   
Investigational 
 and administered SC. Self-administration made by 
the subject at the subject’s home is contemplated only if unusual circumstances, such as public health 
emergency (i.e. pandemic with an infectious agent) or natural disasters, arise. 
Duration of Treatment: 
Up to 200 weeks of continued tildrakizumab treatment from the parent study, followed by an EoT/Follow-up 
assessment at Week 208 (4 years), or approximately 4 weeks after last dose of IMP for those withdrawing 
early. 

 
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Name of Sponsor/Company: 
Sun Pharma Global FZE 
Individual Study 
Table Referring to Part of the 
Dossier: 
 
 
Volume: 
 
Page: 
(For National Authority Use Only) 
Name of Product: 
Tildrakizumab 
Name of Active Ingredient: 
Tildrakizumab 
Concomitant Medications, Supportive Care, and Study Restrictions: 
Permitted medications include: 
• 
Acetaminophen, except within 24 hours before a scheduled study efficacy evaluation, 
• 
Non-steroidal anti-inflammatory drugs or low potency opioids,  
• 
Methotrexate or leflunomide.  Subjects may not be receiving both treatments concomitantly, 
• 
Oral corticosteroids (no more than 10 mg for maintenance dose), 
• 
Non-drug therapy (including but not limited to physical therapy, massage, diet, exercise, emollients, and 
joint taping). 
Use of and adjustment of permitted medication is permitted throughout the study per Investigator discretion 
and therapeutic needs of the subject. 
In accordance with the parent study, subjects are prohibited from use of the following at the time of written 
informed consent for and during the long-term extension study: 
• 
High potency opioid analgesics (e.g., methadone, hydromorphone, or morphine) for the treatment of 
arthritis (allowed for treatment of other conditions for periods of up to 2 weeks), 
• 
Sulfasalazine, 
• 
Systemically administered calcineurin inhibitors (e.g., cyclosporine, tacrolimus), 
• 
Azathioprine, 
• 
Parenteral corticosteroids including intramuscular or intra-articular administration (topical, ophthalmic, 
intra-nasal, and inhaled corticosteroids are permitted) for the treatment of arthritis (allowed for treatment 
of other conditions for periods of up to 2 weeks),  
• 
Live vaccines. 
Any prohibited treatments must be discontinued prior to IMP initiation for the long-term extension study. 
Additionally, subjects must not use systemic immunosuppressive therapies including commercially available 
or investigational therapies for psoriasis (PsO) and/or PsA such as: 
• 
Use of all anti-tumor necrosis factor agents, including etanercept, 
• 
Use of B-cell and T-cell depleting/inhibiting agents, 
• 
Use of any other commercially available or investigational biologic therapies (other than tildrakizumab) 
for PsO and/or PsA within 3 months or 5 half-lives (whichever is longer) prior to or during IMP in the 
long-term extension study, 
• 
Use of apremilast, or other approved or investigational medications for the treatment of current condition 
which are not identified as permitted therapies, 
• 
Use of secukinumab, ustekinumab, ixekizumab, brodalumab, or any drug targeting interleukin (IL)-17, 
IL-23, or the IL-12/IL-23-shared p40 molecule. 
Variables: 
All endpoints will be presented for the measured time points indicated in the flow diagram of the study design. 
Pharmacokinetics:  Serum tildrakizumab concentration data. 
Safety:  The following data will be collected for assessment of safety: 
• 
AEs. 

 
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5 
TABLE OF CONTENTS 
1 
TITLE PAGE ......................................................................................................... 1 
2 
SIGNATURE PAGES ........................................................................................... 2 
3 
GENERAL INFORMATION ................................................................................ 3 
4 
STUDY SYNOPSIS .............................................................................................. 5 
5 
TABLE OF CONTENTS ..................................................................................... 12 
5.1 
List of Tables .......................................................................................... 15 
5.2 
List of Figures ......................................................................................... 15 
6 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ........................ 16 
7 
INTRODUCTION ............................................................................................... 18 
7.1 
Background ............................................................................................. 18 
7.2 
Rationale ................................................................................................. 19 
7.2.1 
Rationale for Dose ............................................................................. 19 
7.2.2 
Rationale for Study ............................................................................ 20 
8 
STUDY OBJECTIVES ........................................................................................ 21 
8.1 
Primary Safety Objectives ...................................................................... 21 
 
 
9 
INVESTIGATIONAL PLAN .............................................................................. 22 
9.1 
Overall Study Design and Plan ............................................................... 22 
9.1.1 
Description ......................................................................................... 22 
9.1.2 
Schedule of Assessments ................................................................... 25 
9.1.2.1 
Blood 
Samples 
for 
Determination 
of 
Anti-Drug 
Antibodies .......................................................................... 28 
9.1.2.2 
Blood Samples for Determination of Serum Concentrations 
of Tildrakizumab (Pharmacokinetics) ................................ 28 
9.1.3 
Study Assessments ............................................................................. 28 
9.1.3.1 
All Study Subjects .............................................................. 28 
9.2 
Discussion of Study Design .................................................................... 31 
9.2.1 
Risk/Benefit and Ethical Assessment ................................................ 32 
9.2.2 
Early Termination .............................................................................. 33 
9.3 
Selection of Study Population ................................................................ 33 
9.3.1 
Inclusion Criteria ............................................................................... 33 
9.3.2 
Exclusion Criteria .............................................................................. 33 
9.3.3 
Strategies for Subject Recruitment and Retention ............................. 35 
9.3.4 
Withdrawal of Subjects ...................................................................... 35 

 
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9.3.5 
Investigational Medicinal Product Discontinuation........................... 36 
9.3.6 
Lost to Follow-Up .............................................................................. 37 
9.3.7 
Discontinuation of Study Sites .......................................................... 37 
9.3.8 
Discontinuation of Study ................................................................... 38 
10 
TREATMENT OF SUBJECTS ........................................................................... 39 
10.1 
Identity of Investigational Medicinal product ........................................ 39 
10.1.1 
Administration of Investigational Medicinal Product ........................ 39 
10.2 
Investigational Medicinal Product Packaging and Labeling .................. 39 
10.2.1 
Packaging ........................................................................................... 39 
10.2.2 
Labeling ............................................................................................. 39 
10.2.3 
Storage ............................................................................................... 39 
10.2.4 
Blinding and Randomization of Investigational Medicinal Product .. 39 
10.3 
Procedure for Breaking the Randomization Code .................................. 40 
10.4 
Subject Compliance ................................................................................ 41 
10.5 
Investigational Medicinal Product Accountability ................................. 41 
10.6 
Concomitant Therapy ............................................................................. 41 
11 
ASSESSMENT OF SAFETY .............................................................................. 43 
11.1 
Adverse Events ....................................................................................... 43 
11.1.1 
Definitions ......................................................................................... 43 
11.1.1.1 Adverse Event .................................................................... 43 
11.1.1.2 Serious Adverse Event ....................................................... 43 
11.1.1.3 Adverse Events of Special Interest ..................................... 44 
11.1.1.4 Overdose ............................................................................. 45 
11.1.1.5 Product Quality Complaint ................................................. 45 
11.1.1.6 Planned Hospitalization ...................................................... 45 
11.1.1.7 Incident ............................................................................... 45 
11.1.1.8 Recording of Adverse Events ............................................. 45 
11.1.1.9 Causal Assessment ............................................................. 46 
11.1.1.10 Abnormal 
Laboratory 
Values/Vital 
Signs/12-Lead 
Electrocardiograms ............................................................. 49 
11.1.1.11 Anaphylaxis ........................................................................ 50 
11.1.1.12 Pregnancy ........................................................................... 50 
11.1.2 
Reporting of Serious Adverse Events ................................................ 51 
11.1.2.1 Safety Reporting to Sponsor............................................... 52 

 
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11.1.2.2 Safety Reporting to Health Authorities, Independent Ethics 
Committees/Institutional 
Review 
Boards 
and 
Investigators ....................................................................... 52 
11.2 
Safety Endpoints ..................................................................................... 53 
11.3 
Laboratory Assessments ......................................................................... 53 
11.3.1 
Clinical Laboratory Tests .................................................................. 53 
11.3.2 
Pregnancy Testing ............................................................................. 54 
11.4 
Assessment of Suicidal Ideation and Behavior ...................................... 54 
11.5 
Electrocardiogram Assessments ............................................................. 54 
11.6 
Physical Examination ............................................................................. 55 
11.7 
Vital Signs .............................................................................................. 55 
11.8 
Anti-Drug Antibodies ............................................................................. 55 
11.9 
24/7 Medical Emergency Coverage for Urgent Protocol-related Medical 
Questions ................................................................................................ 56 
12 
STATISTICAL EVALUATION ......................................................................... 57 
12.1 
Sample Size and Power .......................................................................... 57 
12.2 
Statistical Methods.................................................................................. 57 
12.2.1 
Study Subject Data ............................................................................ 57 
12.2.2 
Efficacy Endpoints ............................................................................. 57 
12.2.3 
Safety Endpoints ................................................................................ 57 
12.3 
Description of Statistical Analyses ......................................................... 58 
12.3.1 
Safety Analysis .................................................................................. 58 
12.3.2 
Pharmacokinetic Analysis ................................................................. 60 
12.3.3 
Interim Analysis................................................................................. 60 
12.3.4 
Data Safety Monitoring Board ........................................................... 60 
12.3.5 
Clinical Adjudication Committee ...................................................... 60 
13 
DIRECT ACCESS TO SOURCE DATA/NOTES .............................................. 62 
14 
QUALITY CONTROL AND QUALITY ASSURANCE ................................... 63 
14.1 
Conduct of the Study .............................................................................. 63 
14.2 
Study Monitoring .................................................................................... 63 
15 
ETHICS ............................................................................................................... 64 
15.1 
Independent Ethics Committee/Institutional Review Board .................. 64 
15.2 
Written Informed Consent ...................................................................... 64 
15.3 
Data Safety Monitoring Board................................................................ 64 
16 
DATA HANDLING AND RECORD KEEPING ............................................... 65 
16.1 
Case Report Forms/Source Data Handling ............................................. 65 
16.2 
Retention of Essential Documents .......................................................... 65 

 
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17 
FINANCING AND INSURANCE ...................................................................... 66 
18 
PUBLICATION POLICY ................................................................................... 67 
19 
CONFLICT OF INTEREST POLICY ................................................................ 68 
20 
SIGNATURE OF INVESTIGATOR .................................................................. 69 
21 
REFERENCE LIST ............................................................................................. 70 
22 
APPENDICES ..................................................................................................... 71 
22.1 
CASPAR (Classification criteria for Psoriatic ARthritis) Criteria ......... 71 
22.2 
American College of Rheumatology 20/50/70 Response Criteria ......... 71 
22.2.1 
Joint Counts ....................................................................................... 72 
22.2.2 
Physician Global Assessment of Disease Activity ............................ 72 
22.2.3 
Patient Global Assessment of Disease Activity ................................. 72 
22.2.4 
Patient Pain Assessment .................................................................... 72 
22.2.5 
Health Assessment Questionnaire - Disability Index (HAQ-DI)....... 72 
22.3 
Biomarkers .............................................................................................. 73 
5.1 
List of Tables 
Table 9-1 
Schedule of Assessments for PsA Subjects ................................................ 26 
 
5.2 
List of Figures 
Figure 9-1 
Flow Diagram of the Study Design ............................................................ 25 
 

 
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6 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
ACR(20/50/70) 
The proportion of subjects achieving a 20/50/70% reduction 
from Baseline in American College of Rheumatology response 
criteria 
ADA 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse event of special interest 
 
 
ASaT 
All Subjects as Treated 
AUC 
area under the curve 
 
 
 
 
 
 
CAC 
Clinical Adjudication Committee 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CPMP 
Committee for Proprietary Medicinal Products 
CRP 
C-reactive protein 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture 
EoT 
End of Treatment 
ESR 
erythrocyte sedimentation rate 
EUDRACT 
European Union Drug Regulatory Agency Clinical Trial 
EUQPPV 
European Union Qualified Person for Pharmacovigilance 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HAQ-DI 
Health Assessment Questionnaire Disability Index 
hsCRP 
high sensitivity C-reactive protein 
IA 
interim analysis 
ICF 
Informed Consent Form 
IEC 
Independent Ethics Committee 
ICH 
International Council for Harmonisation  
IgG1 
immunoglobulin G1 
IL 
Interleukin 
IMP 
investigational medicinal product 

 
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IRB 
Institutional Review Board 
IV 
Intravenous 
IVRS 
interactive voice response service 
LTE 
Long-term Extension 
MACE 
Major Adverse Cardiovascular Events 
NOAEL 
no-observed-adverse-effect-level 
 
 
PASI75 
proportion of subjects achieving a 75% reduction from Baseline 
in Psoriasis Area and Severity Index 
 
 
PGA 
Physician Global Assessment 
PI 
Principal Investigator 
PK 
Pharmacokinetic 
PQC 
product quality complaint 
PsA 
psoriatic arthritis 
PsO 
Psoriasis 
PT 
preferred term 
PtGA 
Patient Global Assessment 
Q 
Every 
QTcB 
QT corrected according to Bazett’s formula 
QTcF 
QT corrected according to the Fridericia formula 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SD 
standard deviation 
SF-36 
36-item Short Form 
SJC44 
swollen joint count of 44 joints 
SOP 
Standard Operating Procedure 
TB 
Tuberculosis 
TEAE 
Treatment-emergent adverse event 
TJC46 
tender joint count of 46 joints 
VAS 
Visual Analog Scale 
 

 
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human exposures obtained from the Phase 1 studies.  
 
.  The human exposure at steady-state for the 
Phase 2/3 dosing paradigm (once Q12 weeks) was estimated by the observed exposure of 
AUC0-∞ (1130 and 1280 µg*day/mL) following a SC single-dose of 200 mg in Phase 1 clinical 
studies (P05776 and P06303), respectively.  
 
 
 
  
 
 
 
 
 
To date, tildrakizumab has been well tolerated at doses up to 200 mg Q12 weeks and no 
dose -related toxicities have been observed.  The available accrued safety data from Phase 1 to 
Phase 3 studies in subjects with PsO supports the continued conduct of the long-term extension 
studies in PsO, and further study of tildrakizumab in subjects with moderate-to-severe chronic 
plaque PsO at doses up to and including 200 mg SC.  In PsA Phase 2 study, there was no 
statistical advantage of therapeutic efficacy observed in a higher dose of tildrakizumab 200 mg 
over tildrakizumab 100 mg.  Therefore, the dose regimen of tildrakizumab 100 mg, Q12 weeks 
was chosen for the long-term extension study.  The current data also support the conduct of 
clinical studies in-patient populations where IL-23 is anticipated to play a pathogenic role in 
inflammatory disease such as PsA, AS, and related conditions.  
7.2.2 
Rationale for Study 
The parent Phase 2 study is the first to be conducted with tildrakizumab in subjects exclusively 
with PsA, and the first to include a dosing regimen of 200 mg SC Q4 weeks.  As tildrakizumab 
is in development for the PsO indication (Phase 3 completed, long-term safety studies 
ongoing), and substantial pharmacokinetic (PK) and pharmacodynamics data exist that can 
inform dose selection used in the parent studies, evaluation of long-term safety, tolerability, 
and efficacy is necessary in these disease areas where suppression of the IL-23 pathway is 
relevant, and where patients may require life-long treatment options.  The study will include 
subjects with PsA from the Phase 2 study evaluating these subject population (e.g., future 
Phase 3 studies).  The study will provide this patient population with the opportunity for 
continued use of a treatment that has afforded clinical benefit across an approximate 52˗week 
period during their parent study. 

 
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8 
STUDY OBJECTIVES 
8.1 
Primary Safety Objectives 
To assess the long-term safety of tildrakizumab when administered to PsA subjects by 
evaluation of: 
• Incidence and intensity of all AEs, 
• Changes in vital signs, laboratory assessments, electrocardiograms (ECGs), and 
Columbia˗Suicide Severity Rating Scale (C-SSRS), 
• Immunogenicity of multiple-dose administration of tildrakizumab in these subjects. 
 
8.2 
Exploratory Objectives 
• 
 
 

 
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9 
INVESTIGATIONAL PLAN 
9.1 
Overall Study Design and Plan 
9.1.1 
Description 
This is a long-term extension study of tildrakizumab in subjects with PsA who have previously 
completed the treatment period of studies with tildrakizumab.  Eligible PsA subjects who have 
previously completed the treatment period of Phase 2b study (CLR_16_23) will be entered into 
this long-term extension study.   
The study will be multinational and conducted in approximately 70 study sites.  All study sites 
used in the parent study can enter subjects to this long-term extension study, based on subject 
eligibility.  Up to 286 subjects with PsA could be enrolled from the parent Phase 2 study.  
Treatment allocation will be based upon the dose regimen assigned at the end of the treatment 
period in the parent study, with all subjects receiving tildrakizumab in the long-term extension 
study.  All subjects who meet the inclusion criteria and have completed the parent study 
treatment period (up to Week 48 for the parent Phase 2 study will return for the End of 
Treatment [EoT] visit at Week 52 of the parent study). The eligible subjects will continue to 
be administered one of the following dose regimens – 200 mg Q4W, 200 mg Q12W or 100 mg 
Q12W to maintain the blind of the ongoing parent study to at least Week 52 of the parent study.  
Thereafter, all subjects began migrating to receive 100 mg tildrakizumab SC injection Q12 
weeks in an open-label fashion for up to an additional 4 years provided that they meet clinical 
response criteria (as defined in Section 9.3.1).   
Note: eligibility for the long-term extension study will be based on response criteria at Week 
52 of the parent study [using Week 48 laboratory data from the parent study where relevant for 
calculations] regardless of timing of subject entry.  Subject eligibility for continuation to the 
long-term extension study based on the clinical response criterion will be determined by the 
interactive voice response service (IVRS).  A flow diagram of the study design is presented in 
Figure 9-1 below. 
The study will consist of a Baseline visit (Week 0) which will be the same as Week 52 of the 
parent study, 12-weekly visits (from Week 12) up to approximately 2 years from the start of 
the extension study, followed by 24-weekly visits thereafter (from Week 108) up until 
approximately 4 years after the start of the study (approximately 5 years from the start of the 
parent study). 
The parent Phase 2 study blind status will be retained at the time of the initiation of the 
extension study).  The eligible subjects will continue to be administered one of the following 
dose regimens – 200 mg Q4W, 200 mg Q12W or 100 mg Q12W to maintain the blind of the 
ongoing parent study to at least Week 52 of the parent study.  Thereafter, all subjects begin 
migrating to receive 100 mg tildrakizumab SC injection Q12 weeks in an open-label fashion 

 
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4 weeks after their last administration of IMP.  Subjects who complete treatment to Week 200 
will return for a Follow-up assessment at Week 208 (4 years). 
The primary safety objectives of this study include assessment of the long-term safety of 
tildrakizumab by evaluation of incidence and intensity of AEs, and changes in vital signs, 
laboratory assessments, ECGs, C-SSRS, and immunogenicity data. 
No independent assessor is needed to assess efficacy measurements.  There will be no efficacy 
assessments during the LTE study. The Principal Investigator (PI)/designee will be responsible 
for performing safety evaluations.  
Clinical Adjudication Committee (CAC) will be established to evaluate cardiovascular events 
(Section 13.3.6). 
End of study is defined as the last visit of the 4-year treatment period (Week 208, 
EoT/Follow˗up) for the last global subject. 
This study will be conducted in compliance with the protocol and with the International 
Council for Harmonisation (ICH) of Technical Requirements for Pharmaceuticals for Human 
Use guidelines on Good Clinical Practice (GCP). 

 
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Table 9-1 
Schedule of Assessments for PsA Subjects 
Visita 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
 
1Y 
BL 
 
 
 
 
 
2Y 
 
 
 
3Y 
 
 
 
 
4Y 
 
 
 
EoT/
FU 
 
Week (± 7D) 
0b 
8 
20 
32 
44 
56 
68 
80 
92 
104 
116 
128 
140 
152 
164 
176 
188 
200 
208c 
Written informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic informationd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
AEs/Concomitant medicationse 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical/Medication historye 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
IMP administrationf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Hematology/chemistry/urinalysisg 
X 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
Lipidsh 
X 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
Urine pregnancy testi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
hsCRP and ESRi 
X 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
Anti-drug antibodies 
X 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Xj 
PK sampleh 
X 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
C-SSRSk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 

 
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Abbreviations: 
AE = adverse event; BL = Baseline; C-SSRS = Columbia-Suicide Severity Rating Scale; D = days; ECG = electrocardiogram; ESR = erythrocyte 
sedimentation rate; EoT = End of Treatment; FU = Follow-up; hsCRP = high sensitivity C-reactive protein; IMP = investigational medicinal product; 
M = months; PK = pharmacokinetic; PsA = psoriatic arthritis; W = weeks; Y = year(s). 
a 
Visits will be scheduled every 12 weeks in the first two years, followed by every 24 weeks in the last two years.  Collection of AEs and concomitant medications, as well 
as any unscheduled safety assessment deemed appropriate in the opinion of the Investigator to ensure subject safety, will be performed at each visit.  In addition, following 
completion and database lock of the parent PsA Phase 2 study, the long-term extension study will have the option to become open-label for these subjects. 
b 
The BL visit of the study Visit 1 (Week 0, Day 1) will be the same as Visit 16, Week 52 of parent PsA study (or later for subjects who entered the wash-out phase from 
the parent study due to the timing of study site activation of the long-term extension study). 
c 
Subjects who withdraw from IMP at any time will complete the EoT/FU assessments approximately 4 weeks after administration of the last dose of IMP. 
d 
To include body weight and height only.  Other demographic data including date of birth, sex, and ethnicity will be obtained from the parent study. 
e 
Report all AEs, SAEs, and concomitant medications that occur after signing of the Informed Consent Form for the long-term study.  Any occurring prior to signing the 
Informed Consent Form for the long-term study should be recorded under Medical/Medication history. 
f 
IMP administration will occur on Day 1 of Week 0; followed by subsequent dosing Q12 weeks.   
g 
Blood samples are to be collected (pre-dose where applicable), after ECG and vital sign measurements.  
h 
At visits where lipids are assessed, the blood samples are to be collected (pre-dose where applicable) after 12 hours fasting, following ECG and vital sign measurements.  
i 
Urine pregnancy tests will be performed by using a urine dip stick.  ESR will be performed at the site using materials supplied by the central laboratory.  hsCRP samples 
will be sent to the central lab and analyzed by central lab.  
j 
A final anti-drug antibodies sample needs to be collected after 20 weeks from last dose. 
k 
Evaluations will continue from the parent study using the version with questions referring to ‘since the last visit’.  No lifetime version will be repeated at BL. 
 

 
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9.1.2.1 
Blood Samples for Determination of Anti-Drug Antibodies 
A sample of blood to obtain sufficient serum for ADA determination will be collected prior to 
IMP administration at the specified time points in Table 9-1.  The sample will be collected into 
the appropriate tubes (see the laboratory manual for sample volumes, acquisition, shipping, and 
labeling instructions).  Sample collection times are to be recorded on the electronic Case Report 
Form (eCRF). 
Sample collection time deviations will be determined by the Sponsor using the actual collection 
times provided and do not need to be recorded in the eCRF.  However, any other deviation 
(e.g., missed sample, broken sample, inappropriate sample handling, etc.) must be recorded on 
the comments page of the eCRF. 
9.1.2.2 
Blood Samples for Determination of Serum Concentrations of Tildrakizumab 
(Pharmacokinetics) 
A sample of blood to obtain sufficient serum for tildrakizumab levels and PK assessment will 
be collected prior to IMP administration at the specified time points indicated in Table 9-1.  
The sample will be collected into the appropriate tubes (see the laboratory manual for sample 
volumes, acquisition, shipping, and labeling instructions).  Actual sample collection times are 
to be recorded on the eCRF. 
9.1.3 
Study Assessments 
The schedule of study assessments is presented in Table 9-1 and details of the study procedures 
are provided in Section 11 and Section 12.  The Sponsor or designated Clinical Research 
Organization (CRO) will be notified immediately of any critical deviation from study 
procedures.  All protocol deviations will be routinely examined by the Sponsor and the 
designated CRO. 
The study will consist of a Baseline assessment (Week 52 for the parent Phase 2 study, or later 
for subjects who entered the wash-out phase from the parent study due to the timing of study 
site activation of the long-term extension study) followed by a continued long-term treatment 
period using the same dosing regimen received in the parent study. 
No independent assessor is needed to assess efficacy measurements as there will be no efficacy 
assessments during the LTE study. The PI/designee will be responsible for performing safety 
evaluations. 
9.1.3.1 
All Study Subjects 
9.1.3.1.1 
Baseline Assessments (Day 1) 
Baseline (Day 1) for this long-term extension study is defined in Section 9.1.1. 
Prior to IMP administration, the assessments and procedures listed in Table 9-1 will be 
performed and include: 

 
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• Obtain and document written informed consent. 
• Check inclusion and exclusion criteria (see Section 9.3.1 and Section 9.3.2). 
Discontinue IMP for subjects who fail to show clinical response to treatment (as defined in 
Section 9.3.1 for PsA subjects), in accordance with the IVRS instruction (see 
Section 9.3.5). 
• Demographics to include body weight and height only.  Date of birth, sex, and ethnicity 
will be obtained from the parent study. 
• Record physical examination findings. 
• Record medical and medication history (including any AEs or concomitant medications 
that remain ongoing from the parent study or any relevant observations made at the Baseline 
visit prior to signing the Informed Consent Form (ICF) for this long-term extension study 
[including laboratory test results from Week 48 of the parent study] are to be recorded). 
• Perform a urine pregnancy test by urine dip stick (at the site using materials supplied by 
the central laboratory). 
• Perform safety assessments including: 
− 12-lead ECG, 
− vital signs, 
− C-SSRS, 
− routine safety laboratory assessments (hematology, chemistry, and urinalysis.).  Blood 
samples are to be collected (pre-dose) after ECG and vital sign measurements, 
− lipids (blood samples are to be collected [pre-dose] after 12 hours fasting and after ECG 
and vital sign measurements), 
− erythrocyte sedimentation rate (ESR) will be performed at the site using materials 
supplied by the central laboratory.  High sensitivity C-reactive protein (hsCRP) samples 
will be sent to the central lab and analyzed by central lab.   
These hsCRP/ESR measures will be used for determination of potential AEs should 
they rise unexpectedly. 
• Obtain a PK sample for drug concentration. 
• Obtain a blood sample for ADA testing. 
Following completion of all assessments and providing all study criteria are met, administer 
the first dose of IMP for the long-term extension study (Baseline, Day 1).  Following IMP 
administration, complete the following assessments: 

 
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• AEs, 
• Record concomitant medications. 
9.1.3.1.2 
Treatment Period (Week 0 through Week 200) 
During the 4-year long-term extension treatment period, subjects will receive 100 mg 
tildrakizumab, SC, Q12 weeks dosing regimen as described in Section 9.1.  The assessments 
and procedures listed in Table 9-1 will be performed at 12-weekly intervals to Week 104 then 
24-weekly intervals to Week 200 and include: 
• Record physical examination findings (annually at Weeks 56, 104, 152, and 200 only). 
• Perform a urine pregnancy test by urine dip stick (at the site using materials supplied by 
the central laboratory). 
• Perform safety assessments including: 
− perform a 12-lead ECG (annually at Weeks 56, 104, 152, and 200 only), 
− vital signs (all visits except Week 116, 140, 164, and 188), 
− C-SSRS (all visits except Week 140, 164, and 188), 
− routine safety laboratory assessments (hematology, chemistry, and urinalysis, 
Weeks 20, 56, 104, 152, and 200 only).  Blood samples are to be collected (pre-dose) 
after ECG and vital sign measurements, 
− lipids (Weeks 20, 56, 104, 152, and 200 only), 
− hsCRP and ESR measures at Week 8, 20, 56, 104, 152, and 200 only, to be used for 
determination of potent AEs should they rise unexpectedly (ESR will be performed at 
the site using materials supplied by the central laboratory.  hsCRP samples will be sent 
to the central lab and analyzed by central lab), 
− AEs (all visits), 
− record concomitant medications(all visits), 
• Obtain a PK sample (Weeks 20, 56, 104, 152, and 200 only). 
• Obtain a blood sample for ADA assessments (Weeks 20, 56, 104, 152, and 200 only). 
• Administer IMP (Weeks 0, 8, 20, 32, 44, 56, 68, 80, 92, 104, 116, 128, 140, 152, 164, 176, 
188, and 200). 
9.1.3.1.3 
End of Treatment/Follow-Up (Week 208 or Approximately 4 Weeks after Last 
Investigational Medicinal Product Administration) 
Subjects who complete the study and receive the last scheduled IMP administration at 
Week 200 will return for a final Follow-up assessment at Week 208 (4 years).  In addition, 

 
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subjects who withdraw from IMP at any time during this long-term extension study will return 
for the EoT/Follow-up assessment approximately 4 weeks after administration of their last dose 
of IMP. 
The assessments and procedures listed in Table 9-1 will be performed and include: 
• Record physical examination findings. 
• Perform a urine pregnancy test by urine dip stick (at the site using materials supplied by 
the central laboratory). 
• Perform safety assessments including: 
− 12-lead ECG, 
− vital signs, 
− C-SSRS, 
− routine safety laboratory assessments (hematology, chemistry, and urinalysis), 
− lipids, 
hsCRP and ESR measures, to be used for determination of potential AEs should they 
rise unexpectedly (ESR will be performed at the site using materials supplied by the 
central laboratory.  CRP samples will be sent to the central lab and analyzed by central 
lab), 
− AEs, 
− record concomitant medications. 
• Obtain a PK sample.  
• Obtain a blood sample for ADA assessments. A final ADA sample needs to be collected 
after 20 weeks from last dose. 
9.2 
Discussion of Study Design 
Subjects with PsA will be eligible for this long-term extension study if they have completed 
approximately 1 year of treatment in the parent study.  At the time of the first subjects entering 
the long-term extension study, other subjects may still be continuing in the parent Phase 2 
study. 
The study has been developed based on design features used in the ongoing parent Phase 2 
study for PsA subjects as well as ongoing Phase 3 studies for subjects with psoriasis.  No 
efficacy endpoints will be assessed for the study. 
The study has been designed to provide an immediate entry into the long-term phase from the 
end of the parent study with the last assessment from the parent study becoming the Baseline 

 
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assessment of the long-term extension.  This enables scientific evaluation of safety at all 
measured time points beyond completion of treatment in the parent study and comparison back 
to the original Baseline of the parent study.  Subjects who entered the wash-out phase of their 
parent study prior to study site activation of this long-term extension protocol will also be 
eligible for inclusion and will re-initiate the tildrakizumab dose last received in the parent 
study.  The duration of time in the wash-out phase of the parent study prior to entry to the long-
term extension is anticipated to be short, thus enabling continued efficacy assessment across 
the long-term extension study. 
All safety measures are consistent with evaluations used in clinical studies and previous studies 
with tildrakizumab. 
9.2.1 
Risk/Benefit and Ethical Assessment 
This extension study will provide subjects from parent Phase 2 study who receive clinical 
benefit from treatment after approximately 1 year, as determined by eligibility criteria and 
Investigator opinion, opportunity to receive continued long-term tildrakizumab treatment for 
up to a further 4 years.  Subjects from other studies may also be eligible for entry to this 
long-term extension study, hence offering extended use of effective dosing regimens. 
Subjects will only be eligible for continuation into this long-term extension study if they 
complete the treatment period of the parent study (Week 48 for parent Phase 2 studies, with 
return for the EoT assessment at Week 52), meet defined clinical response criteria and, in the 
opinion of the Investigator, would gain clinical benefit from long-term continuation of 
tildrakizumab. 
The study has also been designed to minimize potential risks to subjects; all subjects will 
undergo Screening procedures at the start of their parent study aimed at reducing the likelihood 
and impact of any such risks.  In addition, regular safety monitoring during the treatment period 
of the parent study and this long-term extension study for all subjects will ensure that any 
unanticipated effects of study participation are identified promptly and managed appropriately.  
The design also allows withdrawal of subjects from tildrakizumab at the end of the parent study 
(in accordance with the current parent protocol wash-out phase) and at any time thereafter 
during the extension study if, in the opinion of the Investigator, the subject is no longer 
obtaining sufficient clinical benefit, thus enabling subjects to receive other treatment in 
accordance with local clinical practice. 
Overall, based on data from non-clinical and clinical studies of tildrakizumab to date and the 
risk minimization strategies discussed above, the risk:benefit profile of the current study is 
considered acceptable. 

 
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9.2.2 
Early Termination 
This study may be terminated at any time by the Sponsor if serious side effects should occur, 
if the Investigator does not adhere to the protocol or if, in the Sponsor's judgment, there are no 
further benefits to be achieved from the study.  In this event, the Sponsor will inform the study 
Investigators, institutions and all regulatory authorities. 
9.3 
Selection of Study Population 
9.3.1 
Inclusion Criteria 
Subjects may be included in the study if they meet all of the following criteria: 
1. Subject has provided written informed consent for this long-term extension study. 
2. Subjects with PsA who met the inclusion criteria of the parent study and completed the 
parent study treatment period (e.g., up to Week 48 for the parent Phase 2 study, with return 
for the EoT assessment at Week 52). 
3. PsA subjects who achieved a 20% reduction from Baseline in American College of 
Rheumatology (ACR)20 response criteria at Week 52 (for details see Appendix 22.2), 
AND the subject has received sufficient clinical benefit, in the opinion of the Investigator, 
to support continued treatment with tildrakizumab. 
Note: This criterion using response criteria at Week 52 of the parent study will apply to all 
subjects, including those subjects who enter the study from the wash-out phase of their 
parent study (after Week 52) due to the timing of study site activation of the long-term 
extension study.  
4. No concomitant use of both leflunomide and methotrexate, 
5. No history of active tuberculosis (TB) or symptoms of TB. 
9.3.2 
Exclusion Criteria 
Subjects should be excluded from the study if they meet any of the following criteria: 
1. New onset during the parent study of arthritic conditions other than the subject’s original 
condition. 
2. Female subjects of childbearing potential who do not agree to abstain from heterosexual 
activity or practice a dual method of contraception, for example, a combination of the 
following: (1) oral contraceptive, depo-progesterone, or intrauterine device; and (2) a 
barrier method (condom or diaphragm).  Male subjects with female partners of childbearing 
potential who are not using birth control as described above must use a barrier method of 
contraception (e.g., condom) if not surgically sterile (i.e., vasectomy).  Contraceptive 
methods must be practiced upon entering the study and through 16 weeks after the last dose 

 
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of IMP.  If a subject discontinues prematurely, the contraceptive method must be practiced 
for 16 weeks following final administration of IMP. 
3. Female is pregnant or breastfeeding, or planning to become pregnant or initiate 
breastfeeding while enrolled in the study or up to 16 weeks after the last dose of IMP. 
4. Subject has previously been enrolled in this long-term extension study. 
5. Any condition that in the opinion of the Investigator represents an obstacle for study 
conduct and/or represents a potential unacceptable risk for the subject. 
6. Subject has an active infection or history of infections as follows: 
− a serious infection, defined as requiring hospitalization or intravenous anti-infectives 
within 8 weeks prior to the first IMP dose of the extension study, with the last dose 
having been received within 7 days of start of the extension study, 
− recurrent or chronic infections, e.g., chronic pyelonephritis, chronic osteomyelitis, 
bronchiectasis, or other active infection that, in the opinion of the Investigator, might 
cause this extension study to be detrimental to the subject. 
7. Major chronic inflammatory or connective tissue disease other than PsA (e.g., rheumatoid 
arthritis, systemic lupus erythematosus, Lyme disease, or gout, Crohn’s disease, etc). 
8. Known diagnosis of fibromyalgia, regional pain syndromes or active uveitis/symptomatic 
inflammatory bowel disease requiring therapy. 
9. Subject has any concurrent medical condition or uncontrolled, clinically significant 
systemic disease (e.g., renal failure, heart failure, hypertension, liver disease, diabetes, or 
anemia) that, in the opinion of the Investigator, could cause continued treatment to be 
detrimental to the subject. 
10. Subject has a known history of infection with hepatitis B, hepatitis C, or human 
immunodeficiency virus during the parent study. 
11. Subject had myocardial infarction, unstable angina pectoris, or ischemic stroke within the 
past 6 months prior to the first IMP dose for this extension study. 
12. Subject has any active malignancy, including evidence of cutaneous basal or squamous cell 
carcinoma or melanoma. 
13. Subject has a history of malignancy EXCEPT treated and considered cured cutaneous basal 
or squamous cell carcinoma, in situ cervical carcinoma, OR in situ breast ductal carcinoma. 
14. Subjects with a history of alcohol or drug abuse during the parent study. 
15. Significant risk of suicidality at the Baseline assessment (Section 9.1.1) of this extension 
study based on the Investigator's judgment or, if appropriate, as indicated by a response of 

 
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"yes" since the last visit to question 4 or 5 in the suicidal section, or any response in the 
behavioral section of the C-SSRS. 
16. Subject has a need for use of a live vaccine within 10 weeks of final anticipated dose of 
IMP for the long-term extension study. 
17. Concomitant use of prohibited medications or use of commercially available or 
investigational biologic therapies (other than tildrakizumab) for PsO and/or PsA (see 
Section 10.6). 
General 
18. Subjects who have been placed in an institution on official or judicial orders. 
19. Subjects who are related to or dependent on the Investigator, Sponsor, or study site such 
that a conflict of interest may arise. 
9.3.3 
Strategies for Subject Recruitment and Retention 
Subject recruitment will be according to satisfaction of eligibility criteria at the end of parent 
study.  The protocol requirements will be approved by an Independent Ethics Committee (IEC) 
or Institutional Review Board (IRB) prior to implementation. 
Regular study monitoring will enable identification of any potential issues related to subject 
retention. 
9.3.4 
Withdrawal of Subjects 
Subjects may voluntarily withdraw consent to participate in the long-term extension 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 IMP 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. 
For safety reasons, and particularly following an AE, Week 208 (EoT/Follow-up) assessments 
should be conducted if the withdrawn subject is willing to undergo the assessments.  Subjects 
who discontinue the study due to an AE considered related to study drug should be followed 
as described in Section 12.1.1.1. 

 
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The appropriate personnel from the study site and designated CRO will assess whether IMP 
should be discontinued for any subject whose treatment code has been broken inadvertently. 
The Investigator must also contact the IVRS to register the subject’s discontinuation from IMP. 
9.3.5 
Investigational Medicinal Product Discontinuation 
Subjects may voluntarily discontinue IMP for any reason at any time, or completely withdraw 
from the study (see Section 9.3.4).  Subjects who consent will undergo the EoT/Follow-up 
assessment approximately 4 weeks after administration of the last dose of IMP.  
At any time during this long-term extension study, subjects not deriving sufficient clinical 
benefit in the opinion of the Investigator should be discontinued from IMP.  Investigators 
should monitor the clinical benefit of each subject in an ongoing manner throughout the study 
in order to make the determination as to whether it is appropriate for them to continue to 
participate. 
IMP must be discontinued under the following circumstances and further steps need to be 
discussed with the medical monitor: 
• A serious adverse event (SAE), drug reaction or complication, or an unacceptable AE, 
whether attributed to IMP or not, that precludes continuation of treatment with IMP.  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) during study 
(treatment may be continued at the discretion of the subject and Investigator, and in 
consultation with the medical monitor), 
• Subjects who develop suicidal behavior (Section 12.4), 
• 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, site, or the study. 
The derivation of clinical response (at Week 52 for the Phase 2 parent study) will be made 
within the IVRS system using information provided by the study site.  The IVRS system will 
determine the subject's eligibility to continue into the long-term extension study.  Subjects who 
fail to meet eligibility criteria at the end of their parent study will not be eligible to continue to 
the long-term extension study in accordance with the IVRS instruction, and would continue in 
the Follow-up period of their parent study. 

 
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Reasons for Temporary Discontinuation of Investigational Medicinal Product 
Investigational medicinal product may be temporarily suspended in the event of: 
• Clinically important laboratory abnormalities, 
• Subjects who develop suicidal ideation (Section 12.4), 
• Other intercurrent illnesses or major surgery, 
• Use of prohibited treatment (according to inclusion criteria of the parent study, 
Section 9.3.1 and Section 9.3.2), 
• Any other protocol deviation that results in a significant risk to the subject's safety, 
• Sponsor decision. 
After a laboratory abnormality leading to suspension of dosing normalizes sufficiently, IMP 
may resume at the discretion of the PI in consultation with the medical monitor.  Similarly, 
IMP may resume after a prohibited medication leading to suspension of dosing is discontinued.  
A decision to discontinue IMP and/or to reinstitute IMP should be discussed with the medical 
monitor.  The Investigator may suspend IMP at any time, even without consultation with the 
medical monitor if the urgency of the situation requires immediate action and if this is 
determined to be in the subject's best interest.  However, the medical monitor should be 
contacted as soon as possible in any case of IMP discontinuation.  Resumption of IMP after 
temporary discontinuation should always be discussed with the medical monitor. 
9.3.6 
Lost to Follow-Up 
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status.  This includes follow-up with persons authorized by the subject.  Lost to follow-up is 
defined by the inability to reach the subject after a minimum of 3 documented phone calls, 
faxes or emails (not performed on the same day), as well as a lack of response by the subject 
to a registered mail letter.  All attempts should be documented in the subject’s medical records.  
If it is determined that the subject has died, the study site will use permissible local methods to 
obtain the date and cause of death and as much other information as can be obtained, including 
post mortem reports. 
Data to be collected at subsequent visits will be considered missing. 
9.3.7 
Discontinuation of Study Sites 
Study site participation may be discontinued if Sun Pharma Global FZE or designee, the 
Investigator or IRB/IEC of the study site judges it necessary for medical or safety reasons 
consistent with applicable laws, regulations and GCP.  Sun Pharma Global FZE or designee 
may also discontinue the study site or study country should there be a change in the personnel 
(or structure) of the site or political (or economic) environment of the country such that 

 
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continuation of the study in the site or country may negatively impact the study or no longer 
serves the primary objective of the study. 
9.3.8 
Discontinuation of Study 
The study will be discontinued if Sun Pharma Global FZE or designee judges it necessary for 
medical, safety, or business reasons consistent with applicable laws, regulation and GCP. 

 
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10 
TREATMENT OF SUBJECTS 
10.1 
Identity of Investigational Medicinal product 
10.1.1 
Administration of Investigational Medicinal Product 
Investigational medicinal product will be supplied as 
 and 
administered SC.  All subjects will be dosed at the same time points to maintain the study blind 
of the parent study where applicable (see Section 10.2.4).  All subjects will be receiving 
tildrakizumab in accordance with their parent study dose regimen until at least Week 52 in the 
parent study and will transition to tildrakizumab 100 mg Q12 weeks thereafter there will be no 
placebo comparator group in this study.   
If a subject misses a visit and/or a scheduled dose of IMP, the study site must reschedule a visit 
to ensure the dose of IMP is taken as soon as possible within the visit window.  If after 
2 attempts to reschedule or the visit window was missed and the subject still is not able to take 
the dose, the Sponsor should be contacted to determine if the subject should be discontinued 
from the study. 
10.2 
Investigational Medicinal Product Packaging and Labeling 
10.2.1 
Packaging 
Each 
of IMP contains 1 mL of solution.  A 
 of tildrakizumab contains 100 mg 
(100 mg/mL) of active drug. 
10.2.2 
Labeling 
Medication labels will comply with the legal requirements of each country and be printed in 
the local language.  They will supply no information about the subjects. 
10.2.3 
Storage 
All drug supplies for this study must be stored under refrigerated conditions (2ºC to 8ºC) and 
according to labeled storage conditions.  Until dispensed for administration to subjects, the 
IMP will be stored in a securely locked area, accessible to authorized personnel only.  If a study 
nurse is selected to administer IMP in a home setting (Section 9.1.3.3), the study IMP should 
be stored and transported in accordance with the study recommendations.  The IMP should not 
be stored at the subject’s home and should accompany the study nurse on the day of the 
scheduled visit. 
10.2.4 
Blinding and Randomization of Investigational Medicinal Product 
Subjects will be not be randomized and will enter the long-term extension study with one fixed 
dose regimen of tildrakizumab, 100 mg at Week 52 of the parent study.  However, subject 
numbers based on allocation from an IVRS system will remain in place from the parent study 
until such time the blind is no longer required to be maintained. 

 
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A copy of the randomization code with true treatment allocations will be held by the designated 
CRO during the study.  Another randomization list (containing kit number and treatment) will 
be provided to clinical supplies.  The randomization codes associated with each subject will be 
disclosed to PK analysts who will keep PK results confidential until treatment completion of 
the parent study (for Phase 2 parent study, this will be following completion and database lock 
of all PsA subjects). 
The long-term extension study is designed initially to maintain as last dosing regimen in the 
parent study followed by a regimen of 100 mg Q12 week, in an open-label fashion as blinding 
of IMP is no longer necessary to maintain.  If a subject does not receive the scheduled dose, 
every effort should be made to administer the dose as soon as possible (see Section 10.1.1). 
All safety assessments will be administered by the study coordinator or PI/designee. 
Should a situation arise where unblinding is required, the Investigator at that study site may 
perform immediate unblinding via the IVRS without the need for communication with the 
Sponsor.  This can only occur in emergency situations (Section 10.3). 
At the time of the first IA for this extension study, the Phase 2 parent study will have been 
unblinded and hence no considerations of maintenance of blind will be necessary for those 
cohorts of subjects. 
10.3 
Procedure for Breaking the Randomization Code 
Subjects, study site personnel, persons performing the assessments, and data analysts will 
remain blind to the identity of the treatment from the time of randomization until such time the 
long-term study can become open-label for the relevant cohort of subjects (Section 9.1.1). 
Emergency treatment code breaks should only be undertaken when it is essential to treat the 
subject safely and efficaciously.  Most often, IMP discontinuation and knowledge of the 
possible treatment assignments are sufficient to treat a study subject who presents with an 
emergency condition.  Emergency code breaks are performed using the IVRS.  When the 
Investigator contacts the system to break a treatment code for a subject, he/she must provide 
the requested subject identifying information and confirm the necessity to break the treatment 
code for the subject.  The Investigator will then receive details of the IMP for the specified 
subject and a fax or email confirming this information.  The system will automatically inform 
the designated site monitor, medical monitor, and the project manager that the code has been 
broken, but no treatment assignment will be communicated. 
It is the Investigator’s responsibility to ensure that there is a procedure in place to allow access 
to the IVRS in case of emergency.  The Investigator will inform the subject how to contact 
his/her backup in case of emergency when he/she is unavailable.  The Investigator will provide 
the protocol number, IMP name if available, subject number, and instructions for contacting 
the local entity which has responsibility for emergency code breaks to the subject in case an 

 
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emergency treatment code break is required at a time when the Investigator and backup are 
unavailable. 
10.4 
Subject Compliance 
The dosage, timing and mode of administration of IMP may not be changed.  Any departures 
from the intended regimen must be recorded in the eCRF. 
Investigational medicinal product accountability and subject compliance will be documented 
throughout the treatment period using study-specific IMP 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 (Section 10.1.1). 
Deviations from the intended regimen could occur due to: 
• Receiving unscheduled IMP injections, 
• Missing an injection, 
• Receiving the incorrect IMP dose. 
10.5 
Investigational Medicinal Product Accountability 
Records shall be maintained of the delivery of IMP to the study sites, the inventory at the study 
sites, the use of each subject and the return to the Sponsor. 
These records shall include dates, quantities, batch numbers, expiry dates, and the unique code 
numbers assigned to the IMP and to the study subjects. 
The Investigator shall be responsible for ensuring that the records adequately document that 
the subjects were provided the doses specified in the protocol and that all IMP received from 
the Sponsor is reconciled.  All IMP must be returned to the Sponsor at the end of the study. 
10.6 
Concomitant Therapy 
Subjects should abide by inclusion and exclusion restrictions for this long-term extension 
study. 
Permitted medications include: 
• Acetaminophen, except within 24 hours before a scheduled study efficacy evaluation, 
• Non-steroidal anti-inflammatory drugs or low potency opioids (e.g., tramadol),  
• Methotrexate or leflunomide, 
• Oral corticosteroids (no more than daily 10 mg for maintenance dose), 
• Non-drug therapy (including but not limited to physical therapy, massage, diet, exercise, 
emollients, and joint taping).. 

 
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Use of and adjustment of permitted medication is permitted throughout the study per 
Investigator discretion and therapeutic needs of the subject. 
In accordance with the parent study, subjects are prohibited from use of the following at the 
time of written informed consent for and during the long-term extension study: 
• High potency opioid analgesics (e.g., methadone, hydromorphone, or morphine) for the 
treatment of arthritis (allowed for treatment of other conditions for periods of up to 
2 weeks), 
• Sulfasalazine, 
• Systemically administered calcineurin inhibitors (e.g., cyclosporine, tacrolimus), 
• Azathioprine, 
• Parenteral corticosteroids including intramuscular or intra-articular administration (topical, 
ophthalmic, intra-nasal, and inhaled corticosteroids are permitted) for the treatment of 
arthritis (allowed for treatment of other conditions for periods of up to 2 weeks),  
• Live vaccines. 
Any prohibited treatments must be discontinued prior to IMP initiation for the long-term 
extension study. 
During this long-term extension study, subjects must not use systemic immunosuppressive 
therapies including commercially available or investigational therapies for PsO or PsA such 
as: 
• Use of all anti-tumor necrosis factor agents, including etanercept, 
• Use of B-cell and T-cell depleting/inhibiting agents, 
• Use of any other commercially available or investigational biologic therapies (other than 
tildrakizumab) for PsO and/or PsA within 3 months or 5 half-lives (whichever is longer) 
prior to or during IMP in the long-term extension study, 
• Use of apremilast, or other approved or investigational medications for the treatment of 
current condition which are not identified as permitted therapies, 
• Use of secukinumab, ustekinumab, ixekizumab, brodalumab, or any drug targeting 
interleukin (IL) 17, IL 23, or the IL-12/IL-23-shared p40 molecule. 
 

 
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11 
ASSESSMENT OF SAFETY 
The timing and frequency of safety assessments are described in Section 9.1.2 and 
Section 9.1.3. 
11.1 
Adverse Events 
The definitions for AEs and SAEs are provided in Section 11.1.1.  The PI is responsible for 
ensuring all personnel involved in the study are familiar with the content of this section. 
11.1.1 
Definitions 
11.1.1.1 
Adverse Event 
An AE is defined as “any untoward medical occurrence in a subject, or clinical investigation 
subject administered a pharmaceutical product, and which does not necessarily have a causal 
relationship with this treatment.  An AE can therefore be any unfavorable and unintended sign, 
symptom or disease temporally associated with the use of a medicinal (investigation) product, 
whether or not related to the medicinal (investigational) product”. 
Any relevant observations made at the Baseline visit (including laboratory test results, and until 
the ICF is signed) are to be recorded on the AE eCRF, but will not be considered treatment-
emergent AEs (TEAEs) for the long-term extension study, and will be reported separately from 
TEAEs.  A TEAE includes any relevant observations following signing of the ICF for the 
long˗term extension study, and will be recorded as an AE in the subject’s AE eCRF; this 
includes physical examination findings, clinically relevant abnormal vital signs, clinically 
relevant laboratory abnormalities, and clinically relevant ECG findings.  An AE relating to a 
pre˗existing condition or ongoing at the start of the long-term extension study will only be 
recorded as a TEAE if there is a worsening of the pre-existing condition during the long-term 
study conduct with regard to nature, intensity or frequency. 
An adverse drug reaction is an “untoward and unintended response to an IMP related to any 
dose administered”. 
All AEs judged by either the reporting Investigator or the Sponsor as having a reasonable causal 
relationship to a medicinal product qualify as adverse drug reactions.  The expression of 
“reasonable causal relationship” means to convey in general that there are facts or arguments 
which suggest a causal relationship.  Subjects who discontinue the study due to an AE 
considered related to study drug should be followed until the event is resolved, considered 
stable, or the Investigator determines the event is no longer clinically significant. 
11.1.1.2 
Serious Adverse Event 
An SAE is defined as, but is not limited to, an event that: 
• Results in death, 

 
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Death is not an AE in itself, but an outcome.  The cause of the death is the AE which 
resulted in death. 
• 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. 
• Requires in-patient hospitalization or prolongs 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) will not 
be considered an SAE, unless any of the above criteria are fulfilled over the course of the 
hospitalization due to unplanned complications.  "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. 
• 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. 
• Is a congenital anomaly/birth defect, 
• 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. 
11.1.1.3 
Adverse Events of Special Interest 
The events of severe infections (defined as any infection meeting the regulatory definition of a 
SAE or requiring intravenous antibiotics whether or not reported as a serious event), 
malignancies (including non-melanoma and melanoma skin cancer), confirmed Major Adverse 
Cardiovascular Events (MACE), and drug-related hypersensitivity reactions) will each be 

 
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identified a priori as an AE of special interest (AESI) for summarizing in this study.  Major 
Adverse Cardiovascular Events include non-fatal stroke, non-fatal myocardial infarction, and 
cardiovascular death.  All MACE events will be evaluated and adjudicated by a CAC 
(Section 12.3.4).  An AESI must be reported as if it were an SAE (Section 11.1.2) 
11.1.1.4 
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.  Every overdose must 
be reported to the designated pharmacovigilance/safety services within 24 hours of awareness, 
irrespective of whether the overdose was associated with an AE/SAE. 
Overdose in this study is specifically defined as any dose greater than the intended protocol 
dose (Section 10.1.1).  In case of overdose, it is recommended that the subject be monitored 
for any signs or symptoms of adverse reactions or effects and appropriate symptomatic 
treatment be instituted immediately. 
11.1.1.5 
Product Quality Complaint 
A product quality complaint (PQC) is related to a potential quality issue during manufacturing, 
release testing, stability monitoring, dose preparation, storage, or distribution of the product or 
delivery system.  In addition, it includes any reports in which a suspicion of 
counterfeit/tampering exists.  It is important to note that not all PQCs involve a subject.  A 
PQC should be reported within 24 hours, using the details provided in Section 11.1.2. 
11.1.1.6 
Planned Hospitalization 
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. 
11.1.1.7 
Incident 
A device-related incident is any product complaint that led to or might have led to death or 
serious deterioration of health/serious injury/serious illness for the user of the product or any 
other person.  Note that "device" refers to the 
for this study.  The incident should be 
reported within 24 hours, using the details provided in Section 11.1.2. 
11.1.1.8 
Recording of Adverse Events 
Any relevant observations made before the end of the Baseline visit (prior to signing the ICF 
for this long-term extension study) are to be recorded on the AE eCRF, but will not be 
considered TEAEs and will be reported separately from TEAEs.  Any relevant observations 

 
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made after signing the ICF will be recorded as an AE in the subject's AE eCRF (see 
Section 11.1.1.1). 
For the purposes of this study, any detrimental change in the subject's condition, after the first 
dose of IMP for the long-term extension study and up to completion of the EoT/Follow-up 
visit, should be considered an AE. 
The following variables will be recorded for each AE: verbatim/AE description and date for 
AE start and stop, intensity, seriousness, causality rating, whether or not the AE caused the 
subject to discontinue, and the outcome.  A new AE must be recorded if the intensity of the AE 
changes. 
All AEs/SAEs have to be reported to the Sponsor, whether or not considered causally related 
to the IMP or to the study procedure(s). 
All ongoing AEs/SAEs should be followed up until resolution or stabilization or the last visit 
if in the Investigator's opinion, the AE is unlikely to resolve due to the subject's underlying 
disease. 
At any time after the subject has taken the first dose of IMP, if an Investigator learns of an SAE 
that can be reasonably related to IMP, he/she should promptly notify the Sponsor. 
The Investigator will assess the intensity of AEs based on the following definitions: 
• Mild (awareness of sign or symptom, but easily tolerated), 
• Moderate (discomfort sufficient to cause interference with normal activities), 
• Severe (incapacitating, with inability to perform normal activities). 
It is important to distinguish between serious and severe AEs.  Severity is a measure of intensity 
whereas seriousness is defined by the criteria in Section 11.1.1.2. 
An AE of severe intensity need not necessarily be considered serious.  For example, nausea 
that persists for several hours may be considered severe nausea, but not an SAE.  On the other 
hand, a stroke that results in only a limited degree of disability may be considered a mild stroke 
but would be an SAE. 
For an AE to be a suspected drug-related event, there should be at least a reasonable possibility 
of a causal relationship between the IMP and the AE. 
11.1.1.9 
Causal Assessment 
The relationship of AEs to IMP will be assessed by the Investigator (Global Introspection 
assessment), and will be a clinical decision based on all available information. 

 
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Term 
Definition 
Clarification 
Unrelated 
Those AEs which, after careful consideration, are clearly due to extraneous causes (disease, 
environment, etc.) 
Unlikely 
A clinical event, including 
laboratory test abnormality, with 
a temporal relationship to drug 
administration which makes a 
causal relationship improbable, 
and in which other drugs, 
chemicals or underlying disease 
provide plausible explanations. 
1. It does not follow a reasonable temporal sequence 
(Improbable temporal relationship) from administration 
of the drug.  
2. It could also be explained by subject's concurrent 
disease, environmental factors, medical history, and 
other concomitant drugs or chemicals including 
food-drug interactions. 
Possibly 
A clinical event, including 
laboratory test abnormality, with 
a reasonable time sequence to  
administration of the drug, but 
which could also be explained by 
concurrent disease or other drugs 
or chemicals.  Information on 
drug withdrawal may be lacking 
or unclear. 
1. It follows a reasonable temporal sequence from 
administration of the drug.  
2. It could also be explained by subject's concurrent 
disease, environmental factors, medical history, and 
other concomitant drugs or chemicals (including food-
drug interactions).  
3. There is no information or uncertainty with regard to 
what has happened after stopping the drug. 
Probably 
A clinical event, including 
laboratory test abnormality, with 
a reasonable time sequence to 
administration of the drug, 
unlikely to be attributed to 
concurrent disease or other drugs 
or chemicals, and which follows 
a clinically reasonable response 
on withdrawal (de-challenge).  
Re-challenge information is not 
required to fulfil this definition. 
1. It follows a reasonable temporal sequence from 
administration of the drug.  
2. It could not be readily explained (unlikely) by the 
subject's concurrent disease, environmental factors, 
medical history, and other concomitant drugs or 
chemicals including food-drug interactions.  
3. It disappears or decreases in intensity on cessation or 
reduction in dose or on administration of a specific 
antagonist wherever possible. There are important 
exceptions when an AE does not disappear upon 
discontinuation of the drug, yet drug relatedness clearly 
exists.  
4. No re-challenge information is available or possible. 
Certain 
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. 
1. It follows a plausible time sequence to drug intake; this 
means that there is a positive argument in sufficient 
detail to support the view that the drug is causally 
involved, pharmacologically or pathologically e.g., 
pharmacokinetics and type of reaction.   
2. It could not be explained by subject's concurrent 
disease, environmental factors, medical history, and 
other concomitant drugs or chemicals including 
food-drug interactions (i.e., no alternative causes).  
3. It disappears or decreases in intensity on cessation or 
reduction in dose or on administration of a specific 
antagonist wherever possible.  
4. It is an objective and specific medical disorder or a 
recognized pharmacological phenomenon for instance 
‘grey baby syndrome’ and chloramphenicol or 
anaphylaxis immediately after the administration of a 

 
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Term 
Definition 
Clarification 
drug that had been given previously. This means that 
any other event is automatically excluded and can never 
qualify for ‘Certain’ (even in the case of a positive re-
challenge observation).   
5. It reappears on re-administration of the drug (only if 
ethically correct i.e. in case of non-serious and easily 
treatable AEs). 
Abbreviations: 
AE(s) = adverse event(s). 
The Investigator should consider the following, before reaching a decision on causality 
assessment: 
• Time relationship between IMP intake and event's onset, 
• De-challenge, 
• Re-challenge, 
• Medical history, 
• IMP, 
• Mechanism of action of IMP, 
• Class effect, 
• Concomitant treatments in use, 
• Withdrawal of IMP, 
• Lack of efficacy/worsening of existing condition, 
• Erroneous treatment with IMP or concomitant medication, 
• Protocol-related process. 
Action taken with IMP due to the AE: 
• None, 
• Drug permanently discontinued, 
• Drug temporarily discontinued, 
• Unknown/not applicable. 
Other action taken: 
• Specific therapy/medication, 
• Surgical medical procedure, 

 
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• (Prolonged) hospitalization. 
Each single AE must be rated by choosing one of the following outcomes: 
• Recovered/resolved, 
• Recovering/resolving, 
• Not recovered/not resolved, 
• Recovered with sequelae/resolved with sequelae, 
• Fatal, 
• Unknown. 
11.1.1.10 Abnormal Laboratory Values/Vital Signs/12-Lead Electrocardiograms 
Laboratory/vital signs/12-Lead ECG abnormalities should be reported as AEs/SAEs if it is 
clinically significant and any of the following criteria are met: 
• Result is associated with signs/symptoms, 
• Requires additional diagnostic testing and/or intervention, 
• Leads to discontinuation or interruption of the IMP. 
Any test result determined to be an error or simple repetition of a laboratory test is not required 
to be reported as an AE. 

 
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11.1.1.11 Anaphylaxis 
The clinical criteria for diagnosing anaphylaxis are as follows: 
Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both 
(e.g. generalized hives, pruritus or flushing, or swollen lips-tongue-uvula) 
AND AT LEAST ONE OF THE FOLLOWING: 
a) Respiratory compromise (e.g. dyspnea, wheeze-bronchospasm, stridor, reduced PEF, or hypoxemia), 
b) Reduced BP or associated symptoms of end-organ dysfunction (e.g. hypotonia [collapse], syncope, or 
incontinence). 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that subject (minutes 
to several hours): 
a) Involvement of the skin-mucosal tissue (e.g. generalized hives, pruritus or flushing, or swollen lips-tongue-
uvula), 
b) Respiratory compromise (e.g. dyspnea, wheeze-bronchospasm, stridor, reduced PEF, or hypoxemia), 
c) Reduced BP or associated symptoms (e.g. hypotonia [collapse], syncope, or incontinence), 
d) Persistent gastrointestinal symptoms (e.g. crampy abdominal pain, or vomiting). 
3. Reduced BP after exposure to known allergen for that subject (minutes to several hours): 
a) Infants and children: low systolic BP (age specific) or >30% decrease in systolic BP, 
b) Adults: systolic BP of <90 mm Hg or >30% decrease from that person’s Baseline. 
Abbreviations: 
BP = blood pressure; PEF = peak expiratory flow 
Data source: 
Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, et al. 
Second symposium on the definition and management of anaphylaxis: Summary report – Second National 
Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium.  J Allergy Clin 
Immunol 2006;117(2):391-7. 
11.1.1.12 Pregnancy 
Pregnancy itself is not regarded as an AE unless there is suspicion that the IMP may have 
interfered with the effectiveness of a contraceptive medication.  If a pregnancy is reported for 
a subject, no further IMP 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 new-born, 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. 

 
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Pregnancy outcomes must be collected for the female partners of any males who took IMP in 
this study.  Consent to report information regarding these pregnancy outcomes should be 
obtained from the female partner. 
Pregnancies must be reported to the designated pharmacovigilance/safety services using the 
reporting details provided in Section 11.1.2 within 24 hours of awareness. 
11.1.2 
Reporting of Serious Adverse Events 
All SAEs must be reported according to ICH GCP or local regulations, applying the regulation 
with the stricter requirements. 
Investigators and other site personnel must inform the designated pharmacovigilance/safety 
services of any SAE that occurs during the course of the study (from the time of written 
informed consent until 30 days after the last EoT/Follow-up visit), whether or not it is 
considered causally related to the IMP or to the study procedure(s), and within 24 hours of 
when he/she becomes aware of it.  An SAE with an onset day greater than 30 days from the 
EoT/Follow-up visit will be recorded only for fatal SAEs and those deemed by the Investigator 
to be drug-related or AESIs (Section 11.1.1.3).  The Investigator should make every effort to 
obtain follow-up information on the outcome until the event is considered resolved, chronic 
and/or stable. 
If a non-serious AE becomes serious, this and other relevant follow-up information must also 
be provided to the designated CRO within 24 hours as described above.  The start date of the 
SAE is not the start date, but the date when the AE becomes serious; analogously, the stop date 
is the date when any seriousness criterion is no longer applicable, not the date when the AE is 
resolved. 
All SAEs will also be recorded in the eCRF.  The Investigator is responsible for informing the 
Ethics Committee of the SAE as per local requirements. 
Paper SAE forms should be completed at the site and faxed/emailed to the designated 
pharmacovigilance/safety services or emailed to the global email distribution list within 
24 hours of awareness of the event. 
SAE and AESI reports should be sent or faxed to the designated pharmacovigilance/safety 
services provided in Section 3. 
There may be situations when an SAE (or AESI) has occurred and the Investigator has minimal 
information to include in the initial SAE report.  However, it is very important that the 
Investigator always makes an assessment of causality for every event prior to transmission of 
the SAE Report Form.  Minimum criteria are identifiable subject (number), a suspect product 
(i.e., IMP or concomitant medication), an identifiable reporting source (Investigator/study site 
identification), and an event or outcome that can be identified as serious.  The Investigator may 

 
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responsible for promptly notifying the concerned IEC/IRB of any Safety Reports provided by 
the designated pharmacovigilance/safety services and of filing copies of all related 
correspondence in the Investigator Site File. 
11.2 
Safety Endpoints 
All safety endpoints are listed in Section 12.3.1. 
11.3 
Laboratory Assessments 
Laboratory measurements for blood chemistry, hematology, and urinalysis will be performed 
according to Table 9-1.  Specific details not mentioned in this section (including shipping 
requirements) are included in the laboratory manual. 
For visits where lipid panel laboratory parameters will be assessed (see Table 9-1), blood 
samples are to be collected (pre-dose where applicable) after 12 hours fasting, and after ECG 
and vital sign measurements. 
11.3.1 
Clinical Laboratory Tests 
Unless otherwise indicated, all chemistry and hematology parameters will be analyzed using a 
central laboratory.  The following parameters will be collected: 
Laboratory Testing Profile 
Tests Included 
Blood Chemistry 
Sodium, potassium, chloride, bicarbonate/CO2, blood 
urea nitrogen, serum creatinine, fasting glucose, 
albumin, alkaline phosphatase, AST, ALT, total 
bilirubin, direct bilirubin, indirect bilirubin, total 
protein, calcium, gamma-glutamyl transferase, 
creatine kinase 
Hematology 
Hemoglobin, hematocrit, WBC with differentials 
(monocytes, eosinophils, basophils, neutrophils, 
lymphocytes) as an absolute value, RBC count, 
platelet count, ESRa 
Urinalysis 
Specific gravity, pH, semi-quantitative “dipstick” 
evaluation of glucose, protein, bilirubin, ketones, 
leukocytes, blood 
 
Microscopy and/or culture to be performed if 
clinically indicated or if urinalysis results positive 
(blood, protein or leukocyte esterase/WBC). 
 
Urine hCG pregnancy testing for women of 
childbearing potentiala; may be repeated more 
frequently than indicated if required by local 
practice, if a menstrual cycle is missed, or if potential 
pregnancy is suspected. 

 
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Lipid Panel 
Total cholesterol, low density lipoprotein, high 
density lipoprotein, triglycerides, apolipoprotein A-1, 
B 
Acute-phase Reactants 
hsCRP 
Abbreviations: 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; CO2 = carbon dioxide; 
ESR = erythrocyte sedimentation rate; hCG = human chorionic gonadotropin; hsCRP = high 
sensitivity C-reactive protein; RBC = red blood cells; WBC = white blood cells. 
a 
Urine pregnancy tests and ESR will be performed at the study site using materials supplied by the central 
laboratory. 
11.3.2 
Pregnancy Testing 
For female subjects of childbearing potential, a serum pregnancy test will be performed at the 
Screening visit of the parent study only.  Urine pregnancy test with sensitivity of at least 
25 mIU/mL, will be performed according to the Schedule of Assessments (Table 9-1).  If at 
any point during the study there is a case of a positive urine human chorionic gonadotropin 
test, the subject will have IMP stopped and will be withdrawn from the study. 
Pregnancy tests will also be performed whenever 1 menstrual cycle is missed during the 
treatment period (or when potential pregnancy is otherwise suspected), to confirm the subject 
has not become pregnant during the study.  Pregnancy tests may also be repeated as per request 
of IECs/ IRBs or if required by local regulations. 
11.4 
Assessment of Suicidal Ideation and Behavior 
Subjects will be assessed for suicidal ideation and behavior at Baseline (Section 9.1.1) and each 
subsequent visit using the C-SSRS since Last Visit version.  There are 5 questions relating to 
levels of suicidal ideation which prompt questioning about suicidal behavior or intensity of 
ideation, depending on response.  Subjects acknowledging active thoughts of self-harm but 
lacking an articulated plan for doing so are classified at the intermediate risk level; those 
presenting a defined self-harm plan or lacking needed impulse control are judged to be at the 
high-risk level.  Subjects who develop suicidal ideation during the study rated as high-risk 
according to the above classification must be temporarily discontinued from receiving IMP and 
referred promptly for psychiatric evaluation.  Subjects rated as displaying the intermediate level 
of suicidal ideation should receive psychological support and be assessed on an individual 
basis.  All individuals assessed as exhibiting suicidal behavior, except preparatory acts, must 
discontinue IMP permanently.  The presence of non-suicidal self-injurious behavior should be 
assessed on an individual basis. 
11.5 
Electrocardiogram Assessments 
Computerized 12-lead ECG recordings will be obtained at scheduled study visits after the 
subject has rested for at least 5 minutes in the supine position.  ECG data will be submitted to 
a central laboratory for measurement.  The Investigator will document the occurrence of any 
clinically significant 12-lead ECG abnormalities within the eCRF (AE module) based on 

 
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correlation between the central reading report and clinical findings.  Repeat measurements will 
be performed if needed. 
The following ECG parameters will be obtained directly from the computerized 12-lead ECG 
recordings: rhythm, ventricular rate, P-R interval (the portion of the ECG between the onset of 
the P-wave and the QRS-complex), QRS duration and QT/QTcF where, according to the 
Fridericia formula (QTcF), is the observed QT interval (the time from the beginning of the 
Q-wave to the end of the T-wave) divided by the cubed root of the R-R interval (interval from 
the peak of a QRS-complex to the peak of the next) in seconds: 
𝑄𝑄𝑇𝑇𝑇𝑇𝑇𝑇= 𝑄𝑄𝑄𝑄
√𝑅𝑅𝑅𝑅
3
൘
 
 
 
 
QTcB (QT corrected according to Bazett’s formula) will also be recorded, where: 
𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄= 𝑄𝑄𝑄𝑄
√𝑅𝑅𝑅𝑅
൘
 
 
 
 
11.6 
Physical Examination 
A standard complete physical examination will be performed at the weeks specified in 
Table 9-1.  The following parameters and body systems will be examined and any 
abnormalities described: height, weight, general appearance, skin (presence of rash), head, ears, 
eyes, nose, throat, lungs (auscultation), heart (auscultation for presence of murmurs, gallops, 
or rubs), lower extremity examination, abdomen (palpation and auscultation), neurologic 
(mental status, station, gait, reflexes, motor and sensory function, and coordination), and lymph 
nodes.  Any clinically significant changes from Baseline (after signing of the ICF for the long-
term extension study) should be recorded as AEs. 
11.7 
Vital Signs 
Body temperature (oral/tympanic or axillary), systolic and diastolic cuff blood pressure 
(measured after at least 5 minutes in the supine position), and pulse rate (measured after at least 
5 minutes in the supine position) will be recorded according to the Schedule of Assessments 
(Table 9-1).  Automatic or manual devices may be used, but the same device will be used for 
any given subject throughout the study.  The same method of measuring body temperature will 
be used throughout the study.  The same arm will be used for all measurements.  All devices 
must hold valid calibration at the time of use. 
11.8 
Anti-Drug Antibodies  
The presence of ADA for tildrakizumab will be assessed at the time points specified in 
Table 9-1.  Samples will be collected as detailed in Section 9.1.2.1.  Sample testing will be 
conducted as specified in the laboratory manual. 

 
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12 
STATISTICAL EVALUATION 
12.1 
Sample Size and Power 
The sample size of this study is determined by the number of subjects who rollover from the 
parent PsA study.  No power is calculated because the primary objective is to assess the long-
term safety of tildrakizumab. 
12.2 
Statistical Methods 
The All Subjects as Treated (ASaT) population consists of all subjects who entered the 
extension study.  The ASaT is the primary population for safety/tolerability, efficacy, and PK 
analyses.  The analysis will be based on the treatment subjects actually received. 
All endpoints will be presented for the measured time points provided in Table 9-1.  In addition, 
all data collected for subjects who entered the wash-out period of the parent study (whilst 
awaiting start of the long-term extension study at their study site) will be valid for data 
presentation.  This includes data collected at visits beyond Week 52 of the parent study and 
prior to the Baseline visit of the long-term extension study. 
12.2.1 
Study Subject Data 
Subject disposition and demographic data for subjects in the extension study will be 
summarized descriptively. 
Exposure and compliance with IMP will be summarized descriptively. 
Incidence of concomitant medication use will be summarized by World Health Organization 
Drug dictionary coded terms - Anatomical Therapeutic Chemical (ATC) classification and 
preferred name. 
12.2.2 
Efficacy Endpoints 
No efficacy endpoints will be measured. 
12.2.3 
Safety Endpoints 
The following data will be collected for assessment of safety: 
• AEs, 
• AESI, 
• Laboratory assessments, 
• Suicidal ideation and behavior (C-SSRS), 
• Vital signs, 
• ECG, 

 
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• Physical examination, 
• ADA to tildrakizumab. 
12.3 
Description of Statistical Analyses 
All the safety and efficacy data will be summarized descriptively through appropriate data 
tabulations and descriptive statistics.  For continuous variables, unless otherwise stated, the 
number of available observations (n), mean, standard deviation (SD), median, and range will 
be provided.  For categorical variables, the number and percentage in each category will be 
displayed. 
The last value of a variable taken before the first dose of IMP in parent study will be used as 
the original Baseline value.  The last value before the first dose of IMP in the long-term 
extension study will be used as the LTE Baseline value.   Unless otherwise specified, missing 
or dropout data will not be imputed for the purpose of data analysis. 
A more detailed description of study analyses will be presented in the Statistical Analysis Plan 
(SAP). 
12.3.1 
Safety Analysis 
The subjects in this long-term extension study will be summarized separately according to 
parent PsA studies and indication.  Any additional summaries including pooling of indications, 
common dosing regimens, or studies will be provided in the SAP. 
The subjects will be summarized based on the actual treatment received at specific time points 
when applicable. 
Adverse Events 
AEs will be coded using the most recent version available of the Medical Dictionary for 
Regulatory Activities (MedDRA). 
Due to the various durations of exposure to a treatment, the exposure-adjusted AE incidence 
rate (per 100 subject-years) will be summarized by treatment group.  The incidence of AEs will 
be summarized by system organ class and PT.  If a subject experiences the same PT multiple 
times then the event will be counted only once for the greatest intensity during a treatment 
period.  Separate tables will be presented by intensity; AEs considered to be related to IMP by 
the Investigator will be summarized similarly. 
AEs of special interest will be summarized descriptively. 
All AEs will be presented in full in a comprehensive listing including subject number, treatment 
(or sequence) received, intensity, seriousness, action taken, outcome, relationship to treatment, 
treatment received at AE onset, onset/stop and duration.  Details of SAEs and AEs leading to 

 
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withdrawal will be listed separately.  A more detailed description regarding presentation of AE 
data will be provided in the SAP. 
Clinical Laboratory 
Clinical laboratory parameters will have observed values and changes from Baseline 
summarized at each scheduled visit by treatment group. 
Values outside the normal range will be categorized as above the normal range (H) or below 
the normal range (L) based on the laboratory's reference range and these will be flagged in the 
listings of individual subject data. 
Vital Signs 
Vital sign observed values and changes from Baseline will be summarized at each scheduled 
visit by treatment group. 
ECG 
The overall ECG interpretation will be summarized by presenting the number and percentage 
of subjects with "Normal" "Abnormal, not clinically significant", and "Abnormal, clinically 
significant". 
ECG parameters (e.g., QTcF) will have observed values and changes from Baseline 
summarized at each scheduled visit by treatment group. 
Physical Examination 
Physical examination results will be summarized with incidence of "Normal" and "Abnormal" 
by body system at each scheduled visit by treatment group. 
Assessment of Suicidal Ideation and Behavior 
Subjects will be assessed for suicidal ideation and behavior using C-SSRS. 
The C-SSRS consists of 2 major aspects: Suicidal Ideation and Suicidal Behavior.  The 
following endpoints will be used to analyze C-SSRS data: 

 
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• Presence of Suicidal Ideation:  Set to 1 if any ideation is present and 0 otherwise, 
• Presence of Suicidal Behavior:  Set to 1 if any type of suicidal behavior is present and 
0 otherwise, 
• Suicidal ideation score: Defined as the maximum suicidal ideation category (1-5) present 
on the C-SSRS at the assessment.  A score of 0 is assigned if no ideation is present.  
The number (%) of subjects with presence of suicidal ideation and behavior will be summarized 
at each assessment time.  The C-SSRS data will be summarized using worst-case shift from 
baseline tables. 
ADA to Tildrakizumab 
For each subject, tildrakizumab serum concentrations and ADA sample results are matched to 
actual sampling times and treatment.  Subjects are grouped based on the actual treatment 
received.  The anti-tildrakizumab immunogenicity status of evaluable subjects, along with titer 
will be summarized by dose level. 
 
 
12.3.2 
Pharmacokinetic Analysis 
Serum tildrakizumab concentration data will be listed by individual subject and summarized 
by visit.  The subjects will be summarized based on the ASaT population with the actual 
treatment received at a specific visit.  All samples for PK and ADA studies will also be saved 
for future safety or biomarkers analysis as deemed appropriate by Sun Pharmaceuticals.  A list 
of biomarkers is provided in Appendix 22.3. 
PK parameters may be used to refine previous PK models. 
12.3.3 
Interim Analysis 
An IA to review safety data will be performed at one year of this long-term extension study.  
Additional IAs may be performed as needed to support reporting requirements or as needed for 
internal decision-making. 
12.3.4 
Data Safety Monitoring Board 
According to FDA Guideline “Establishment and Operation of Clinical Trial Data Monitoring 
Committees” 3, March 2006, a Data Safety Monitoring Board is not required for this extension 
study. 
12.3.5 
Clinical Adjudication Committee 
A CAC will evaluate an extensive set of cardiovascular events and all deaths to determine 
which of these meet pre-specified endpoint criteria.  Cardiovascular events for adjudication 

 
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will be identified based on Investigator reports with specific AE terms.  Instructions for 
obtaining source documentation for all events to be adjudicated will be provided to the 
Investigator study sites in a separate document.  All personnel involved in the adjudication 
process will remain blinded to treatment allocation throughout this long-term extension study 
until such time the study may become open-label.  Specific details regarding the cardiovascular 
endpoints to be analyzed, including the endpoint definitions and criteria can be found in the 
Adjudication Committee Charter. 

 
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13 
DIRECT ACCESS TO SOURCE DATA/NOTES 
The Investigator/institution shall provide direct access to source data/documents for 
study-related monitoring, audits, IEC/IRB review and regulatory inspection. 

 
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14 
QUALITY CONTROL AND QUALITY ASSURANCE 
14.1 
Conduct of the Study 
The designated CRO and Sun Pharma Global FZE shall implement and maintain quality control 
and quality assurance procedures with written Standard Operating Procedures (SOPs) to ensure 
that the study is conducted and data are generated, documented and reported in compliance 
with the protocol, ICH GCP, and applicable regulatory requirements. 
This study shall be conducted in accordance with the provisions of the Declaration of Helsinki 
(October 2013)4, United States Food and Drug Administration (FDA, Code of Federal 
Regulations [CFR], Sections 312.50 and 312.56), European Union (Annex 1, Directive 
2001/83/EC) and United Kingdom regulations (The Medicines for Human Use [Clinical Trials] 
Regulations 2004 [No. 1031]), and with ICH GCP (Committee for Proprietary Medicinal 
Products [CPMP] 135/95). 
The Investigator may not deviate from the protocol without a formal protocol amendment 
having been established and approved by an appropriate IEC/IRB, except when necessary to 
eliminate immediate hazards to the subject or when the change(s) involve(s) only logistical or 
administrative aspects of the study.  Any deviations may result in the subject having to be 
withdrawn from the study and render that subject non-evaluable. 
14.2 
Study Monitoring 
The Investigator shall permit the designated CRO site monitor to review study data as 
frequently as deemed necessary to ensure that data are being recorded in an adequate manner 
and that protocol adherence is satisfactory. 
The Investigator will provide access to medical records for the designated CRO site monitor in 
order that entries in the eCRF may be verified.  The Investigator, as part of his/her 
responsibilities, is expected to co-operate with the designated CRO in ensuring that the study 
adheres to GCP requirements. 
The Investigator may not recruit subjects into the study until such time that a visit, or with the 
agreement of the Sponsor, attendance at the Investigator meeting, has been made by a 
Sponsor/designated CRO site monitor to conduct a detailed review of the protocol and eCRF. 

 
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15 
ETHICS 
15.1 
Independent Ethics Committee/Institutional Review Board 
Prior to the start of the study, the Investigator is responsible for ensuring that the protocol and 
ICF have been reviewed and approved by a relevant IEC/IRB.  The IEC/IRB shall be 
appropriately constituted and perform its functions in accordance with FDA, ICH GCP, and 
local requirements as applicable. 
The IEC/IRB shall approve all protocol amendments (except for logistical or administrative 
changes), written informed consent documents and document updates, subject recruitment 
procedures (e.g., advertisements), written information to be provided to the subjects, 
Investigator's Brochure, available safety information, information about payment and 
compensation available to subjects, the Investigator's curriculum vitae and/or other evidence 
of qualifications, and any other documents requested by the IEC/IRB and Regulatory Authority 
(Competent Authority) as applicable. 
15.2 
Written Informed Consent 
The nature and purpose of the study shall be fully explained to each subject (or their legally 
responsible guardian). 
Written informed consent must be obtained from each subject (or guardian) prior to any study 
procedures being performed.  The process of obtaining informed consent must be documented 
in the subject source documents. 
The consent documents to be used for the study shall include all the elements of informed 
consent as outlined in accordance with FDA, ICH GCP, and local requirements as applicable 
and be reviewed and approved by the appropriate IEC/IRB prior to use.  
15.3 
Data Safety Monitoring Board 
According to FDA Guideline “Establishment and Operation of Clinical Trial Data Monitoring 
Committees” 3, Mach 2006, a Data Safety Monitoring Board is not required for this extension 
study.  

 
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16 
DATA HANDLING AND RECORD KEEPING 
16.1 
Case Report Forms/Source Data Handling 
All required study data must be entered in the eCRF created for the study.  This data collection 
tool is a validated electronic data capture (EDC) system that contains a system generated audit 
trail.  Data required according to this protocol are recorded by investigational study site 
personnel via data entry into the internet based EDC software system.  The Investigator shall 
ensure that all data from subject visits are promptly entered into the eCRFs in accordance with 
the specific instructions given.  The Investigator must sign each eCRF to verify the integrity of 
the data recorded.  All internal designated CRO and external investigational study site 
personnel seeking access to the eCRF are supported by a Service Desk (if applicable).  At the 
end of the study all data captured electronically will be provided to the Investigator on 
CD-ROM for archiving at the investigational study site. 
A list of the normal ranges for all laboratory tests to be undertaken forms part of the 
documentation to be collated prior to study start.  It is essential that all samples be analyzed at 
the central laboratory, unless otherwise specified (e.g., ESR). 
The Investigator must maintain source documents, such as laboratory reports, X-rays, ECGs, 
consultation reports, and complete medical history and physical examination reports.  All 
information in the eCRF must be traceable to the source documents in the subject’s file. 
16.2 
Retention of Essential Documents 
The Investigator/institution should maintain the study documents as specified in the ICH 
guidelines on GCP and as required by the applicable regulatory requirements.  The 
Investigator/institution should take measures to prevent accidental or premature destruction of 
these documents. 
Essential documents should be retained 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 until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the IMP.  These documents should be retained for a 
longer period, however, if required by the applicable regulatory requirements or by an 
agreement with the Sponsor.  It is the responsibility of the Sponsor to inform the 
Investigator/institution as to when these documents no longer need to be retained. 

 
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17 
FINANCING AND INSURANCE 
The Sponsor shall carry an insurance policy to cover compensation of subjects' health injuries 
arising from the study.  The subject may be treated (and other necessary measures taken) at the 
study site and/or another medical institution if a study-related injury is incurred.  If it is 
necessary to compensate for the treatment, the Sponsor will cover the cost.  The Sponsor shall 
not impose on the subject the burden of proving the causal relation between the study and the 
injury. 
If any of the following is confirmed, the Sponsor may refuse or restrict the payment of the 
compensation: 
• A serious GCP or protocol deviation by the Investigator or Sub-Investigator (except 
deviation medically necessary to avoid an immediate hazard to the study subjects), 
• Intentional act or negligence on the part of the Investigator or Sub-Investigator or 
malpractice thereby, 
• Injury caused by unlawful act or delinquency of a third party, 
• Injury caused by intentional act or negligence of the subject. 
If compensation becomes necessary for a study-related injury, the study site will promptly 
notify the Sponsor and will co-operate with the Sponsor and its insurer (or their legal 
representatives) in their handling thereof. 

 
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18 
PUBLICATION POLICY 
The Sponsor shall retain the ownership of all data. When the study is complete, the Sponsor 
shall arrange the analysis and tabulation of data.  A final clinical study report shall then be 
prepared, which may be used for publication, presentation at scientific meetings, or submission 
to regulatory authorities.  All proposed publications based on this study must conform to the 
Sponsor's approval requirements. 
The Sponsor assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov in the United States.  In addition, upon study 
completion and finalization of the clinical study report, the results of this study will be 
submitted for publication and/or posted in a publicly accessible database of clinical study 
results. 
 

 
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19 
CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical.  Therefore, any actual conflict(s) of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this study will be 
disclosed and managed.  Furthermore, persons who have a perceived conflict of interest will 
be required to have such conflicts managed in a way that is appropriate to their participation in 
the study.  The study leadership in conjunction with the Sponsor has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest. 

 
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20 
SIGNATURE OF INVESTIGATOR 
I agree to conduct the study outlined above in accordance with the terms and conditions of the 
protocol, ICH guidelines on GCP and with applicable regulatory requirements.  All information 
pertaining to the study shall be treated in a confidential manner. 
 
 
 
 
 
 
((Type name and job title))   
 
 
 
 
 
Date (day/month/year) 
 

 
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21 
REFERENCE LIST 
1. MK-3222 (SCH 900222) Investigator’s Brochure, Edition 8, 06 October 2017. 
2. Randomized, Double-Blinded, Placebo-Controlled, Parallel-Design, Dose-Range Finding 
Study of Subcutaneous SCH 900222 in Subjects with Moderate-to-Severe Chronic Plaque 
Psoriasis (Protocol No. P05495).  16 July 2010. 
3. Guidance for Clinical Trial Sponsors; Establishment and Operation of Clinical Trial Data 
Monitoring Committees. U.S. Department of Health and Human Services, Food and Drug 
Administration, Center for Biologics Evaluation and Research (CBER), Center for Drug 
Evaluation and Research (CDER), Center for Devices and Radiological Health (CDRH), 
March 2006.  
4. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human 
Subjects. 
 
Available 
at 
http://www.wma.net/en/20activities/10ethics/10helsinki/ 
DoH-Oct2013-JAMA.pdf.  Accessed 07 October 2016. 
5. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al.  American 
College of Rheumatology Preliminary Definition of Improvement in Rheumatoid Arthritis.  
Arthritis Rheum.  1995;38(6):727-35. 

 
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22 
APPENDICES 
All subjects in this long-term study were required to meet the following criteria relating to a 
diagnosis of PsA, in accordance with the parent study inclusion criteria. 
22.1 
CASPAR (Classification criteria for Psoriatic ARthritis) Criteria 
A subject must have inflammatory articular disease (joint, spine or entheseal) and ≥ 3 points 
from the following categories: 
 
Category 
Description 
Points 
Current psoriasis or personal or 
family history of psoriasis 
Current psoriasis: skin or plaque disease confirmed by 
rheumatologist or dermatologist 
Personal history: obtained from subject, family physician, 
dermatologist, 
rheumatologist, 
or 
other 
qualified 
healthcare provider 
Family history: presence of psoriasis in 1° or 2° relative 
as reported by subject 
2 (current) 
OR 
1 (history) 
Psoriatic nail dystrophy on current 
examination 
Onycholysis, pitting, hyperkeratosis 
1 
Negative rheumatoid factor 
Any method except latex, but preferably Enzyme-linked 
immunosorbent assay (ELISA) or nephelometry, using 
local laboratory reference range 
1 
Dactylitis (current or on history as 
recorded by rheumatologist) 
Swelling of an entire digit 
1 
Radiographic evidence of 
juxta-articular new-bone formation 
Ill-defined ossification near joint margins but excluding 
osteocyte formation on plain X-rays of the hand or foot 
1 
 
Sensitivity 91.4%; Specificity 98.7% 
Data source: 
Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H; CASPAR Study 
Group.  Classification Criteria for Psoriatic Arthritis: development of new criteria from a large 
international study. Arth Rheum.  2006;54:2665-2673. 
22.2 
American College of Rheumatology 20/50/70 Response Criteria 
The ACR20/50/70 response measures the percentage of subjects with at least a 20/50/70% 
improvement from Baseline in both tender joints (68) and swollen joints (66) along with 
associated percentage improvements in 3 of 5 other items: 1) the PGA of disease activity (as 
measured using a Visual Analog Scale [VAS]), 2) the Patient Global Assessment (PtGA) of 
disease activity (as measured using a VAS), 3) patient pain assessment (as measured using a 
VAS), 4) patient self-assessed disability (as measured using the HAQ-DI), and 5) acute-phase 
C-reactive protein (CRP)5.  A sensitivity analysis will be performed by evaluating 
ACR20/50/70 response calculated using ESR. 

 
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22.2.1 
Joint Counts 
In accordance with the parent studies, the measure used is the ACR joint count initially 
developed for the assessment of patients with rheumatoid arthritis.  The ACR joint count of 
68 tender and 66 swollen joints count will continue to be used in this long-term study and 
includes the majority of joints affected in PsA subjects.  It includes the temporomandibular, 
sternoclavicular, acromioclavicular, shoulder, elbow, wrist (including the carpometacarpal and 
intercarpal joints as 1 unit), metacarpophalangeal, proximal interphalangeal, distal 
interphalangeal, hip, knee, talotibial, midtarsal (including subtalar), metatarsophalangeal, and 
interphalangeal joints of the toes (proximal and distal joints of each toe is counted as 1 unit). 
22.2.2 
Physician Global Assessment of Disease Activity 
The treating physician will evaluate the status of the subject's disease by means of a VAS.  The 
subject will be assessed according to how their current disease is.  The VAS will be anchored 
with verbal descriptors of "very good" to "very poor". 
22.2.3 
Patient Global Assessment of Disease Activity 
The subject will assess their current global status of PsA by means of a VAS ("Considering all 
the ways your disease affects you, on average, how have you been doing today?"), anchored 
with verbal descriptors of "very well" to "very poorly". 
22.2.4 
Patient Pain Assessment  
The subject will assess their level of present pain ("How much pain due to your arthritis are 
you currently experiencing?") using a VAS.  The subject will be asked to rate their pain at that 
time on the scale that is anchored with verbal descriptors of "no pain" to "worst possible pain". 
22.2.5 
Health Assessment Questionnaire - Disability Index (HAQ-DI) 
The subject will assess their general disability over the past week using the HAQ-DI 
questionnaire. 
The HAQ-DI is designed to assess subjects’ usual abilities using their usual equipment.  
Subjects usually find the HAQ-DI self-explanatory, and clarifications are seldom required.  
There are 8 categories assessed by the HAQ-DI: 1) dressing and grooming, 2) arising, 3) eating, 
4) walking, 5) hygiene, 6) reach, 7) grip, and 8) common daily activities.  For each of these 
categories, subjects report the amount of difficulty they have in performing 2 or 3 specific 
activities.  The time frame for the disability questions is the PAST WEEK and each question 
can be scored as 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) 
or 3 (unable to do).  The use of aids and devices for these activities is also recorded.  Use of 
any device or aid will result in a minimum score of 2 for that category.  The score for the 
disability index is the mean of the 8 category scores.  If >2 of the categories, or 25%, are 

 
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missing, the scale is not scored.  If <2 of the categories are missing, the sum of the categories 
is divided by the number of answered categories.  A higher score indicates greater disability. 
22.3 
Biomarkers 
The Sponsor, SUN Pharma Global FZE (SUN) would like to perform additional analysis on 
the following remaining blood samples: 
• 
Samples collected to measure anti-drug antibodies (ADA) 
• 
Samples collected to measure how much study medicine is in your blood 
(pharmacokinetics, PK) 
Upon completion of ADA and PK analysis, samples will be used to analyze additional 
biomarkers 
 
Taking part in this optional biomarkers research is voluntary and subjects who sign amended 
informed consent will participate in Biomarker research. Samples will be destroyed once all 
the biomarkers tests have been completed. 
 

 
Sun Pharma Global FZE 
 
22 Jul 2020 
Tildrakizumab 
 
 
Protocol CLR_18_07 
Amendment 1.0 (Final) 
 
Page 74 of 74