Conditions: Chronic Plaque Psoriasis Moderate to Severe Nail Psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 99
Healthy volunteers: no

Brief summary:
Phase 3b study to Assess the Efficacy and Safety of Tildrakizumab in the Treatment of Moderate to Severe Nail Psoriasis

Detailed description:

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: Tildrakizumab intervention 2: Placebo
Intervention descriptions: intervention 1: PART 1: Double-blind Placebo-controlled PART 2: Double-blind Active Treatment Extension PART 3: Observational Safety Follow-up intervention 2: PART 1: Double-blind Placebo-controlled PART 2: Double-blind Active Treatment Extension PART 3: Observational Safety Follow-up

Protocol document:
Prot_000.pdf: 
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Assess 
the Efficacy and Safety of Tildrakizumab in the Treatment of Moderate to Severe Nail Psoriasis. 
Document: Study Protocol 
NCT number: NCT03897075 
Document date: 23 Dec 2022 


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TITLE PAGE 
Protocol Title:   
A Multicenter, Randomized, Double-Blind, Placebo-Controlled 
Clinical Study to Assess the Efficacy and Safety of Tildrakizumab in 
the Treatment of Moderate to Severe Nail Psoriasis  
Protocol Number:   
  
TILD-18-19  
Amendment Number:    
Amendment 3, 23-Dec-2022  
Product:   
  
 
Tildrakizumab 
Short Title:   
Efficacy and Safety Profile of Tildrakizumab in Subjects with 
Moderate to Severe Nail Psoriasis  
Study Phase:   
3b  
Sponsor Name:  
Sun Pharmaceutical Industries Limited [SPIL] 
Legal Registered Address:   
SUN HOUSE, CTS No. 201 B/1, 
Western Express Highway, Goregaon (E), 
Mumbai 400063  
 
 
 
 Date of Initial Protocol:   
22 February 2019 
Date of Amendment 1:  
03 Nov 2020  
Date of Amendment 2:  
25 Sep 2021 
Date of Amendment 3:  
23 Dec 2022 
 
 
 
 
 
 
 
 


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TABLE OF CONTENTS 
TABLE OF CONTENTS ..............................................................................................................3 
LIST OF TABLES .........................................................................................................................6 
LIST OF FIGURES .......................................................................................................................6 
ABBREVIATIONS ........................................................................................................................7 
1.0 
PROTOCOL SUMMARY ................................................................................................9 
1.1 
Synopsis ...................................................................................................................9 
1.2 
Schema ...................................................................................................................16 
1.3 
Schedule of Activities ............................................................................................17 
2.0 
INTRODUCTION............................................................................................................20 
2.1 
Background ............................................................................................................20 
2.2 
Study Rationale ......................................................................................................20 
2.3 
Benefit/Risk Assessment .......................................................................................22 
3.0 
OBJECTIVES AND ENDPOINTS ................................................................................24 
4.0 
STUDY DESIGN ..............................................................................................................27 
4.1 
Overall Design .......................................................................................................27 
4.1.1 
PART 1: Double-blind Placebo-controlled (Day 1 to Week 28) ..........27 
4.1.2 
PART 2: Double-blind Active Treatment Extension (Week 28 to 
Week 52) ...............................................................................................28 
4.1.3 
PART 3: Observational Safety Follow-up (Week 52 to Week 72) .......28 
4.2 
Scientific Rationale for Study Design....................................................................29 
4.3 
Justification for Dose .............................................................................................29 
4.4 
End of Study Definition .........................................................................................30 
5.0 
STUDY POPULATION ..................................................................................................31 
5.1 
Inclusion Criteria ...................................................................................................31 
5.2 
Exclusion Criteria ..................................................................................................32 
5.3 
Lifestyle Considerations ........................................................................................34 
5.4 
Screen Failures .......................................................................................................34 
6.0 
STUDY TREATMENT ...................................................................................................36 
6.1 
Study Treatment Administered ..............................................................................36 
6.2 
Preparation/Handling/Storage/Accountability .......................................................37 
6.3 
Measures to Minimize Bias: Randomization and Blinding ...................................37 
6.4 
Study Treatment Compliance ................................................................................38 
6.5 
Concomitant Therapy.............................................................................................38 
6.5.1 
Rescue Medicine ...................................................................................39 
6.5.2 
Allowed Concomitant Medication ........................................................39 


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6.6 
Dose Modification .................................................................................................39 
6.7 
Treatment after the End of the Study .....................................................................39 
6.8 
Excluded Medication .............................................................................................39 
7.0 
DISCONTINUATION OF STUDY TREATMENT AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ......................................................................41 
7.1 
Discontinuation of Study Treatment ......................................................................41 
7.1.1 
Temporary Discontinuation ..................................................................41 
7.2 
Subject Discontinuation/Withdrawal from the Study ............................................42 
7.3 
Lost to Follow-up ...................................................................................................42 
8.0 
STUDY ASSESSMENTS AND PROCEDURES ..........................................................44 
8.1 
Efficacy Assessments.............................................................................................45 
8.1.1 
Nail Psoriasis Severity Index (NAPSI) .................................................45 
8.1.2 
Phy
- Whole body (PGA-S) ..........46 
8.1.3 
Psoriasis Area and Severity Index (PASI) ............................................46 
8.1.4 
Nail Pain Numeric Rating Scale (NRS) ................................................47 
8.1.5 
Total Body Surface Area (BSA) ...........................................................47 
8.1.6 
Visual Medical Scale to Evaluate Nail Psoriasis Severity 
(ViSENPsO) ..........................................................................................47 
8.1.7 
-PGA).....................................48 
8.1.8 
Clinician Global Impression of Change (CGIC) ...................................48 
8.1.9 
Clinician Global Impression of Severity (CGIS) ..................................48 
8.1.10 
Quality of life ........................................................................................48 
8.1.10.1 
Dermatology Life Quality Index (DLQI) ......................................48 
8.1.10.2 
Nail Assessment in Psoriasis and Psoriatic Arthritis QoL 
(NAPPA-QoL) ...............................................................................48 
8.1.10.3 
Patient Global Impression of Change (PGIC) ...............................48 
8.1.10.4 
Patient Global Impression of Change for pain (PGIC-P) ..............49 
8.1.10.5 
Patient Global Impression of Severity (PGIS) ...............................49 
8.1.10.6 
Patient Global Impression of Severity for pain (PGIS-P) ..............49 
8.2 
Safety Assessments ................................................................................................49 
8.2.1 
Physical Examinations ..........................................................................49 
8.2.2 
Vital Signs .............................................................................................49 
8.2.3 
Assessment of Suicidal Ideation and Behavior .....................................50 
8.2.4 
Electrocardiograms ...............................................................................50 
8.2.5 
Tuberculosis Testing .............................................................................50 
8.2.6 
Chest X-ray ...........................................................................................51 
8.2.7 
Clinical Safety Laboratory Assessments ...............................................51 


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8.3 
Adverse Events ......................................................................................................51 
8.3.1 
Time Period and Frequency for Collecting AE and SAE 
Information ............................................................................................52 
8.3.2 
Method of Detecting AEs and SAEs .....................................................53 
8.3.3 
Follow-up of AEs and SAEs .................................................................53 
8.3.4 
Regulatory Reporting Requirements for SAEs .....................................53 
8.3.5 
Pregnancy ..............................................................................................54 
8.3.6 
Adverse Events of Special Interest .......................................................54 
8.3.7 
Events of Clinical Interest .....................................................................55 
8.4 
Treatment of Overdose ..........................................................................................55 
8.5 
Pharmacokinetics ...................................................................................................55 
8.6 
Pharmacodynamics ................................................................................................55 
8.7 
Genetics..................................................................................................................55 
8.8 
Biomarkers .............................................................................................................55 
8.9 
Health Economics or Medical Resource Utilization and Health Economics ........56 
9.0 
STATISTICAL CONSIDERATIONS ...........................................................................57 
9.1 
Statistical Hypotheses ............................................................................................57 
9.2 
Sample Size Determination....................................................................................57 
9.3 
Populations for Analyses .......................................................................................57 
9.4 
Statistical Analyses ................................................................................................58 
9.4.1 
Efficacy Analyses..................................................................................59 
9.4.2 
Safety Analyses .....................................................................................60 
9.4.2.1 
Adverse Events and Serious Adverse Events ................................61 
9.4.2.2 
Physical Examinations, 12-Lead ECG, Vital Signs, and 
Clinical Safety Laboratory Tests (Hematology, Biochemistry, 
and Urinalysis) ...............................................................................61 
9.4.3 
Other Analyses ......................................................................................62 
9.4.4 
Missing Data .........................................................................................62 
9.5 
Interim Analyses (IA) ............................................................................................62 
9.6 
Monitoring Committee...........................................................................................63 
10.0 
REFERENCES .................................................................................................................64 
11.0 
APPENDICES ..................................................................................................................68 
 
Appendix 1: 
Regulatory, Ethical and Study Oversight Considerations..........................68 
Appendix 2: 
Clinical Laboratory Tests ...........................................................................75 
Appendix 3: 
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting .......................................................77 


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Appendix 4: 
Anaphylaxis ...............................................................................................84 
Appendix 5: 
Contraceptive Guidance and Collection of Pregnancy ..............................85 
Appendix 6: 
Definition and Diagnosis of Fungal Nail Infection ....................................89 
Appendix 7:  
Nail Psoriasis Severity Index (NAPSI) ......................................................90 
Appendix 8: 
modified Nail Psoriasis Severity Index (mNAPSI) ...................................91 
Appendix 9: 
-S) .............92 
Appendix 10: 
Psoriasis Area and Severity Index (PASI) .................................................93 
Appendix 11: 
Numeric Rating Scale (NRS) .....................................................................94 
Appendix 12: 
Visual Medical Scale to Evaluate Nail Psoriasis Severity (ViSENPsO) ...95 
Appendix 13: 
Dermatology Life Quality Index (DLQI) ..................................................96 
Appendix 14: 
Nail Assessment in Psoriasis and Psoriatic Arthritis QoL (NAPPA-
QoL) ...........................................................................................................97 
Appendix 15: 
Patient Global Impression of Change (PGIC) ...........................................98 
Appendix 16: 
Patient Global Impression of Change for pain (PGIC-P) ..........................99 
Appendix 17:  
Patient Global Impression of Severity (PGIS) .........................................100 
Appendix 18: 
Patient Global Impression of Severity for pain (PGIS-P) ........................101 
Appendix 19: 
Columbia-Suicide Severity Rating Scale .................................................102 
Appendix 20: 
-PGA): ......................................111 
Appendix 21: 
Clinician Global Impression of Change (CGIC) .....................................112 
Appendix 22: 
Clinician Global Impression of Severity (CGIS) .....................................113 
Appendix 23: 
Signature of Investigator ..........................................................................114 
LIST OF TABLES 
Table 1:  
Schedule of Activities ................................................................................17 
Table 2: 
Study Objectives and Endpoints ................................................................24 
Table 3: 
Study Treatment Details ............................................................................36 
Table 4: 
Excluded Medications/treatments ..............................................................40 
Table 5: 
Analysis Sets ..............................................................................................58 
Table 6: 
Efficacy Analyses ......................................................................................59 
Table 7: 
Protocol-required Safety Laboratory Assessments ....................................75 
LIST OF FIGURES 
Figure 1:  
Study Schema.............................................................................................16 
 
 
 


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ABBREVIATIONS 
Abbreviation  
Definition  
AE  
Adverse event  
AESI  
Adverse event of special interest  
ALT  
Alanine aminotransferase  
AST  
Aspartate aminotransferase  
ATWC 
Active treatment worst case  
BSA  
Body surface area  
CFR  
Code of Federal Regulations  
CGIC 
Clinician Global Impression of Change 
CGIS 
Clinician Global Impression of Severity 
ClinRO 
Clinician-reported outcome measure 
CRF  
Case report form  
CRO  
Contract research organization  
CSR  
Clinical study report  
C-SSRS  
Columbia-suicide severity rating scale  
DBF 
Database Freeze 
DBL 
Database Lock 
DLQI  
Dermatology life quality index  
DMARDs 
Disease-modifying antirheumatic agents 
DMC 
Data Monitoring Committee 
ECG  
Electrocardiogram  
ECI  
Event of clinical interest  
eCRF  
Electronic case report form  
EDC  
Electronic data capture  
ePRO 
electronic patient-reported outcome 
EoS  
End of study  
EoT  
End of treatment  
f-PGA 
Fingernail physician global assessment 
FSH  
Follicle-stimulating hormone  
GCP  
Good clinical practice  
HBsAg  
Hepatitis B surface antigen  
HCV  
Hepatitis C virus  
HIV  
Human immunodeficiency virus  
HRT  
Hormone replacement therapy  
ICF  
Informed consent form  
ICH  
International council for harmonisation  
IEC  
Independent ethics committee  
IL  
Interleukin  
IRB  
Institutional review board  
ITT  
Intent-to-Treat  


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Abbreviation  
Definition  
IV  
Intravenous  
IWRS  
Interactive web response system  
LTBI  
Latent tuberculosis infection  
MACE  
Major adverse cardiovascular events  
MMRM  
Mixed model repeated measures  
mNAPSI 
Modified Nail Psoriasis Severity Index
NAPPAQoL 
Nail assessment in psoriasis and psoriatic arthritis with three 
components: a questionnaire assessing quality of life 
NAPSI 
Nail psoriasis severity index
NRS  
Numeric rating scale  
PASI  
Psoriasis area and severity index  
PFS  
Prefilled syringe  
PGA  
Physician global assessment  
PGA-F 
Physician global assessment fingernail 
PGA-S 
Physician global assessment skin 
PGIC 
Patient global impression of change 
PGIC-P 
Patient global impression of change for pain 
PGIS 
Patient global impression of severity 
PGIS-P 
Patient global impression of severity for pain 
PPS  
Per protocol set  
PRO  
Patient-reported outcome  
QoL  
Quality of life  
SAE  
Serious adverse event  
SAP  
Statistical analysis plan  
SC  
Subcutaneous  
SoA  
Schedule of Activities  
SOP  
Standard operating procedure  
s-PGA 
 
SSRE 
Sample size re-estimation 
TB  
Tuberculosis  
TEAE  
Treatment-emergent adverse event  
TH  
T-helper cell  
TNF  
Tumor necrosis factor  
TNFI 
Tumor necrosis factor inhibitor 
ULN  
Upper limit of normal  
ViSENPsO 
Visual medical scale to evaluate nail psoriasis severity 
VPV 
ViSENPsO Psychometric Validation 
WOCBP  
Woman of childbearing potential  


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1.0 
PROTOCOL SUMMARY  
1.1 
Synopsis  
Protocol Title: A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical 
Study to Assess the Efficacy and Safety of Tildrakizumab in the Treatment of Moderate to 
Severe Nail Psoriasis  
Short Title: Efficacy and Safety Profile of Tildrakizumab in Subjects with Moderate to 
Severe Nail Psoriasis 
Rationale:  
Psoriasis is a chronic inflammatory skin disorder and affects approximately 1% to 2% of people 
worldwide. Nail psoriasis occurs in approximately 50% of patients with plaque psoriasis and is 
associated with pain and discomfort, causing a significant burden to quality of life (QoL) and 
work function. Currently approved biological treatments for moderate to severe plaque psoriasis 
include tumor necrosis factor (TNF) antagonist agents, a p40 (interleukin [IL] 12 and IL 23) 
antagonist, p19 (IL 23) antagonists, and IL-17 antagonist agents. Despite the availability of 
treatment options for plaque psoriasis, nail lesions remain difficult to treat. Thus, there remains 
an unmet need for effective therapeutic options for nail psoriasis.  
Recent studies have demonstrated that IL-23-dependent T-helper (Th)17 cells control much of 
the inflammatory damage that is observed in psoriasis. Based on this rationale, several 
therapeutic anti-IL-23 antibodies were developed and entered into clinical studies. 
Tildrakizumab, an anti-IL 23p19 antibody, demonstrates comparable efficacy in psoriasis to 
other biological compounds in the IL-23 pathway. It has a favorable safety profile and 
convenient dosing at Weeks 0, 4, and every 12 weeks after that.  
treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic 
therapy or phototherapy and in Australia on 06 September 2018 for the treatment of adults with 
moderate to severe plaque psoriasis who are candidates for systemic therapy.  
This study is planned to be a multicenter, randomized, double-blind, placebo-controlled study to 
evaluate the efficacy and safety of tildrakizumab in the treatment of moderate to severe nail 
psoriasis.  
One tool appearing in the US product labeling to assess nail involvement in plaque psoriasis is 
the 5-point 
-F). However, this 
clinician-reported outcome measure (ClinRO) scale has shown poor inter-rater reliability, relying 
on physician experience with nail psoriasis with only sparse textual descriptors to help in 
assessing severity categories (no visual exemplification of the respective severity ratings). In 
addition, the exact form of PGA-F that has supported product labeling is a proprietary measure 


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and is unavailable to SPIL. Given these measurement challenges, there is a need to develop new 
tools that evaluate nail psoriasis severity.  
Given that, a new ClinRO, the Visual Medical Scale to Evaluate Nail Psoriasis Severity 
(ViSENPsO), was developed to assess fingernail pathology severity. A Contract Research 
Organization, ICON, conducted in-depth, semi-structured qualitative interviews with 
dermatologists to support the content validity of the new measure. The interviews were 
complemented by systematic mixed methods, using rating and ranking tasks that have allowed 
the measure development team to ensure professional consensus informs elements of the new 
scale. The overall ClinRO development process will also be complemented by patient interviews 
to aid understanding of how patients experience nail psoriasis severity, contrasting evaluations 
and understandings with those of expert dermatologists.  
The next step is to psychometrically validate the ViSENPsO. A Statistical Analysis Plan (SAP) 
for the ViSENPsO Psychometric Validation (VPV) describing the methodological approaches 
that will be used to psychometrically validate the ViSENPsO in line with Food and Drug 
Administration (FDA) guidance (FDA, 2009; Powers et al., 2017) shall be prepared. The SAP 
for VPV will specifically define the analysis cohort and variables, outline the statistical methods 
and analyses to be conducted on the data, and shall describe the criteria that will be used to 
interpret results. The SAP for VPV will include corresponding unique table shells and an index 
or samples for any other analytic items (e.g., listings, figures, and replicate tables). The 
psychometric validation of the ViSENPsO will use data from SPIL
-18-19 trial to 
evaluate the efficacy and safety of tildrakizumab in the treatment of moderate to severe nail 
psoriasis. 
Objectives and Endpoints  
EFFICACY OBJECTIVES 
EFFICACY ENDPOINTS 
Primary Efficacy Objective 
Primary Efficacy Endpoint 
 
To assess the efficacy of tildrakizumab in 
subjects with moderate to severe nail psoriasis, 
as measured by the proportion of subjects who 
achieve at least a 75% improvement from 
baseline in total-modified Nail Psoriasis 
Severity Index (mNAPSI) at Week 28. . 
 
The proportion of subjects who achieve at least 
a 75% improvement from baseline in total-
mNAPSI at Week 28. 
Secondary Objectives  
Secondary Endpoints  
 
To assess the efficacy of tildrakizumab in the 
treatment of moderate to severe nail psoriasis 
compared with placebo as measured by the 
ViSENPsO at Week 28 (Key secondary 
objective) 
 
- 
 
at 
least a 2-point decrease from baseline at Week 
28 as measured by the ViSENPsO. (Key 
secondary endpoint) 


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EFFICACY OBJECTIVES 
EFFICACY ENDPOINTS 
 
To assess the effect of tildrakizumab on nail pain 
compared with placebo as measured by nail pain 
numeric rating scale (NRS) score at Week 28.  
 
The proportion of subjects with at least 3 point 
decrease from baseline in Nail Pain NRS score 
at Week 28 in subjects with baseline nail pain 
NRS score of > 3* 
 
To assess the effect of tildrakizumab on nail pain 
compared with placebo as measured by nail pain 
numeric rating scale (NRS) score at Week 28. 
 
Change in patient-reported nail pain NRS 
score from Baseline at Week 28 
 
To assess the efficacy of tildrakizumab in the 
treatment of moderate to severe nail psoriasis 
compared with placebo as measured by 
mNAPSI, NAPSI, and ViSENPsO at Week 28. 
 
The proportion of subjects achieving total-
fingernail mNAPSI 90, mNAPSI 100, NAPSI 
75, NAPSI 90, and NAPSI 100 at Week 28.  
 
Change in total-fingernail mNAPSI score from 
baseline at Week 28.  
 
Change in total-fingernail NAPSI score from 
baseline at Week 28. 
 
The proportions of ViSENPsO category results 
at Week 28 compared between treatment 
groups. 
 
To assess the efficacy of tildrakizumab in the 
treatment of plaque psoriasis compared with 
placebo, as measured by Psoriasis Area and 
l 
Assessment-Skin (PGA-S) score and body 
surface area (BSA) involvement at Week 28.  
 
The proportion of subjects achieving PASI 75, 
PASI 90, and PASI 100 at Week 28.  
 
The proportion of subjects achieving a PGA-S 
ast 
a 2-point reduction from baseline to Week 28. 
 
Percentage change in total BSA involvement 
from baseline to Week 28.  
 
To assess the effect of tildrakizumab on nail pain 
compared with placebo as measured by nail pain 
NRS score improvement from baseline at Week 
28.  
 
The proportion of subjects with at least 30% 
decrease in Nail Pain NRS score from Baseline 
at Week 28 in subjects with a baseline nail pain 
NRS score of > 3*.   
Exploratory Objectives  
Exploratory Endpoints  
 To assess the effect of tildrakizumab over time 
at measured time points through Week 52 as 
measured by mNAPSI, NAPSI, Nail Pain NRS, 
BSA, PGA-S, s-PGA, PASI,
  
 
Change from baseline in mNAPSI, NAPSI, 
Nail Pain NRS, BSA, PGA-S, s-PGA, PASI, 
 
 
 
 
To assess the effect of tildrakizumab on QoL as 
measured by:  
o 
Dermatology Life Quality Index (DLQI) 
o 
Nail Assessment in Psoriasis and Psoriatic 
Arthritis QoL (NAPPA- QoL).  
 
Change from Baseline in DLQI score (total and 
6 domain scores) and NAPPA-QoL score at 
measured time points through Week 52.  
 
To assess the effect of tildrakizumab measured 
by using anchor scales: 
o 
Clinician Global Impression of Change 
(CGIC). 
o 
Clinician Global Impression of Severity 
(CGIS) 
o 
Patient Global Impression of Change 
(PGIC).
 Change from baseline in CGIC, CGIS, PGIC, 
PGIC-P, PGIS, and PGIS-P at measured time 
points through Week 52. 


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EFFICACY OBJECTIVES 
EFFICACY ENDPOINTS 
o 
Patient Global Impression of Severity 
(PGIS). 
o 
Patient Global Impression of Severity for 
pain (PGIS-P). 
o 
Patient Global Impression of Change for 
pain (PGIC-P). 
*
be based on average score from 7-daily records at Baseline. 
 
SAFETY OBJECTIVE 
SAFETY ENDPOINT 
 
To assess the safety and tolerability of 
tildrakizumab in subjects with moderate to 
severe nail psoriasis over 52 weeks.  
 The percentage of subjects with incidence, 
seriousness, and severity of all adverse events. 
 The percentage of subjects with severe 
infections defined as any infection meeting 
the regulatory definition of a serious adverse 
event (SAE), or any infection requiring 
intravenous (IV) antibiotics, whether or not 
reported as a serious event as per the 
regulatory definition.  
 The percentage of subjects with malignancies 
(excluding carcinoma in situ of the cervix).  
 The percentage of subjects with non-
melanoma skin cancer.  
 The percentage of subjects with melanoma 
skin cancer.  
 The percentage of subjects with major adverse 
cardiovascular events (MACE).  
 The percentage of subjects with study 
treatment-related hypersensitivity reactions 
(e.g., anaphylaxis, urticaria, angioedema, 
etc.).  
 The percentage of subjects with injection site 
reactions (e.g., pain, erythema, edema, etc.)  
Overall Design:  
This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy 
and safety of tildrakizumab in the treatment of moderate to severe psoriasis of the nails.  
Subjects with a clinical diagnosis of chronic plaque psoriasis for at least 6 months and moderate 
to severe psoriasis of the nails at screening and baseline (
, ViSENPsO of 
) as well as moderate to severe plaque psoriasis at screening and baseline (s-
PGA score of at least 3
) and who are considered candidates for 
systemic therapy will be enrolled in the study.   


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After a screening period of 28 days, all eligible subjects will be randomly allocated (in a 1:1 ratio 
after stratification according to previous use of TNF-alpha inhibitors [yes/no] and baseline body 
weight [<90 kg or >90 kg]) on Day 1 to receive either tildrakizumab 100 mg or placebo by 
subcutaneous (SC) injection on Week 0 (Day 1), 4, and 16. Subjects should receive the first dose 
of study treatment within 24 hours of randomization.   
At Week 16, subjects who experience significant worsening of plaque psoriasis (defined as an 
increase in s-PGA by at least 2 from the baseline measurement) will be eligible for an early 
escape. Subjects selected for early escape by the Principal Investigator at Week 16 will have 
study medication discontinued and will complete the End of Treatment visit assessment, 
followed by the observational safety follow-up period. Subjects entering early escape may be 
replaced to meet the planned evaluable sample size goal for the primary endpoint analysis. 
At Week 28, subjects initially randomized to placebo will be switched over to receive 
tildrakizumab 100 mg at Weeks 28, 32, and 44. Subjects initially randomized to tildrakizumab 
100 mg will continue to receive tildrakizumab at Weeks 28, 40, and 52. In order to maintain the 
blind, subjects in both treatment arms will receive matching placebo injections at specified time 
points as described in the Schedule of Assessment (SoA).  
Subjects who experience significant worsening of plaque psoriasis at Week 28 (defined as an 
increase in s-PGA by, at least 2 from the baseline measurement) will be discontinued from 
treatment. Subjects who do not fulfill this criterion at Week 28 will continue to receive 
tildrakizumab in Part 2, as described above.  
After Week 52 (or early termination of study treatment prior to Week 52), the study treatment 
should be stopped, and the subjects will enter the 20-week observational safety follow-up period 
following the last dose of study treatment. During the follow-up period, subjects should continue 
on study-approved concomitant medications only; however, may be placed on other appropriate 
therapies for safety concerns or significant worsening of psoriasis based on the judgment of the 
Investigator. The subjects will not receive study treatment during the follow-up period.  
ViSENPsO, mNAPSI, NAPSI, NRS, BSA, s-PGA, PGA-S, PASI, CGIC, CGIS, NAPPA-QoL, 
PGIC, PGIS, PGIS-P, PGIC-P, and DLQI. CGIC, CGIS, PGIC, PGIS, PGIS-P, and PGIC-P are 
considered anchor scales in this study.  
Safety assessments, including adverse event (AE)/serious adverse event (SAE) monitoring, vital 
signs, physical examinations, electrocardiograms, and laboratory measurements will be 
performed during the study.  
An interim analysis may be performed that could include an unblinded sample size re-estimation 
(SSRE). Sample size of the study could be increased as a result of this SSRE. In the event of an 
increase in sample size, the total sample size of the study will not exceed a total of approximately 
282 randomized subjects.  


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Week 28 
analysis may be conducted on available data to evaluate safety and efficacy, and a Week-28 
clinical study report (CSR) may be developed after database lock (DBL). In this case, when all 
the randomized patients have either completed the Week 28 evaluations or have stopped study 
participation prior to the Week 28 visit, the first database freeze (DBF) will occur (referred to as 
Week 28 DBF hereafter). When all patients randomized in this trial have either completed the 
Week 72 evaluations or have ceased study participation prior to the Week 72 visit, the second 
DBL will take place [referred to as the Final (Week 72) DBL henceforth], and subsequent CSR 
will be generated. The sponsor might opt to have a single DBL and CSR at the 
Week 72 visit (or early termination prior to Week 72) without a DBL at Week 28. 
A final analysis will be performed when the last subject has completed the study.  
Number of Investigators and Study Centers:  
Up to approximately 35 Investigators and study centers globally, are expected to participate in 
this study.  
Number of Subjects:  
Approximately 96 eligible subjects will be randomly assigned to study treatment for an estimated 
total of 48 subjects per treatment arm. It is assumed up to 10% of the subjects may drop out, 
leaving 43 evaluable subjects per arm for the primary endpoint analysis at Week 28. 
Treatment Groups and Duration:  
The study duration per subject will be approximately 18 to 19 months, and the total duration of 
the study will be approximately 3 years.   
The study consists of a screening period of 28 days, a 52-week treatment period (a 28-week 
double-blind placebo-controlled treatment period followed by a 24-week double-blind, active 
treatment period), and a 20-week observational follow-up period.   
Part 1: Double-blind, placebo-controlled part, where subjects will receive either tildrakizumab 
100 mg (Arm A) or placebo (Arm B) SC at Weeks 0, 4, and 16. At Week 16, subjects who 
experience significant worsening of plaque psoriasis (defined as an increase in s-PGA by at least 
2 from the baseline measurement) will be eligible for an early escape. Subjects selected for early 
escape by the Principal Investigator at Week 16 will have study medication discontinued and will 
complete the End of Treatment visit assessment, followed by the observational safety follow-up 
period. 
Part 2: At Week 28, subjects initially randomized to placebo will be switched over to receive 
tildrakizumab 100 mg at Weeks 28, 32, and 44. Subjects initially randomized to tildrakizumab 
100 mg will continue to receive the active drug at Weeks 28, 40, and 52. In order to maintain the 
blind, subjects in both treatment arms will receive matching placebo injections at specified time 


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points as described in the SoA. Subjects who experience significant worsening of plaque 
psoriasis at Week 28 (defined as an increase in s-PGA by, at least 2 from the baseline 
measurement) will be discontinued from treatment.  
Part 3: After Week 52 (or early termination of study treatment prior to Week 52), subjects will 
enter the 20-week observational safety follow-up period when tildrakizumab treatment will be 
stopped.  
Statistical methods:  
The primary efficacy endpoint is the proportion of subjects who achieve at least a 75% 
improvement from baseline in the total modified Nail Psoriasis Severity Index (mNAPSI). The 
key secondary efficacy endpoint is the proportion of subjects with 
- 
 
at least a 2-point decrease from baseline at Week 28 as measured by 
the ViSENPsO. For each endpoint, the tildrakizumab 100 mg dose will be compared with the 
placebo at Week 28. Both the primary and key secondary efficacy endpoints will be analyzed 
using the Cochran-Mantel-Haenszel (CMH) test, incorporating prior use of TNF-alpha inhibitors 
and baseline body weight as stratifications factors. In addition, the Miettinen and Nurminen 
(M&N) common risk (the response rate) difference between tildrakizumab 100 mg and placebo 
arm, along with the 95% confidence interval (CI) will be estimated. The analyses will be based 
on the Intent-to-treat (ITT) population. All analyses will also be conducted for the Per Protocol 
Set (PPS) populations as supportive.  
Efficacy hypothesis testing will be controlled for multiplicity using a step-down sequential 
testing approach for the primary and key secondary endpoints. If the test on the primary endpoint 
is significant at the alpha = 0.05 level, then the test comparing the key secondary endpoint 
between treatment arms will also be conducted at the 0.05 level. The subsequent test will not be 
conducted if the null hypothesis of the previous test is not rejected.  
Secondary and exploratory efficacy endpoints obtained from Week 28 to Week 52 will be 
evaluated using summary statistics.  
Safety endpoints will be analyzed descriptively based on the safety analysis set (SAF), defined as 
all subjects who received at least 1 dose of study treatment. Subjects will be summarized based 
on the actual treatment they received.   
Intent-to-Treat (ITT): All randomized subjects who were dispensed study treatment, regardless of 
whether treatment was taken by the subject or not. The primary efficacy population will be the 
ITT.   
Per Protocol Set (PPS): All subjects in the ITT population who complete the 28-week placebo-
controlled treatment without any major protocol deviations.  
Safety Analysis Set: All randomized subjects who have taken at least one dose of study treatment, 
based on the treatment received.  


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Sample Size Determination:  
Conservatively assuming the mNAPSI75 response rates between active drugs and placebo of 35 
vs. 10 (Results from a similar therapeutic agent, Adalimumab had shown response rates of 46 vs.
3 ) and assuming Normal Approximation and a Z-test (pooled) for proportions and a two-sided 
3 subjects per treatment arm (for a total 86) will need to be 
randomized in a 1:1 ratio, stratified for prior use of TNF-alpha inhibitors (yes/no) and baseline 
8 subjects in each arm, after 
accounting for up to 10% dropout, will yield at least 80% power. Accordingly, approximately 96 
subjects [48 per arm] shall be randomized in the study. 
Data Monitoring Committee: An independent Data Monitoring Committee (DMC) may be 
established for periodic review of safety data from the study. The composition and 
responsibilities of the DMC will be described in the DMC Charter.  The DMC will have access 
to unblinded data.
 
 
 


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1.3 
Schedule of Activities  
Table 1:  
Schedule of Activities  
 
Screening  
PART 1 
Double-blind Placebo-controlled 
PART 2 
Double-blind Active Treatment 
PART 3 
OSFU 
Week  
  
0 
(Baseline) 
4 
 
8 
12 
16a 
20 
24 
28b 
32 
36 
40 
44 
52c 
EoT 
72 
EoS 
Visit Number  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
Day  
Within 28 
Days 
1 
+/- 
3 days 
+/- 
3 days 
+/- 
3 days 
+/- 
3 days 
+/- 
3 days 
+/- 
3 days 
+/- 
3 days 
+/- 
3 days 
+/- 
7 days
+/- 
7 days 
+/- 
7 days 
+/- 
7 days 
+/- 
7 days 
Written informed consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion criteria  
X 
Xd 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic information  
X 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Vital signs  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEf /Concomitant medications  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical/ Medication history  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest X-rayg  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
QuantiFERONh  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, HbsAg, and HCV serology  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG  
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Randomizationi  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
IWRS entry 
X 
X 
X 
 
 
X 
 
 
X 
X 
 
X 
X 
X 
X 
Study treatment administrationj  
 
X 
X 
 
 
X 
 
 
X 
X 
 
X 
X 
X 
 
Hematology/chemistry/Urinalysisk 
Xl 
X 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
Lipidsk  
 
X 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
Serum pregnancy test  
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Urine pregnancy testm  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
C-SSRSn  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Efficacy assessments 
(ViSENPsO, NAPSI, mNAPSI, 
PGA-S, pain NRS, BSA, and 
PASI)o, p 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
s-PGA q 
X 
X 
 
 
 
X 
 
 
X 
 
 
 
 
 
 
CGIS 
X 
X 
 
 
X 
 
 
 
X 
 
X 
 
 
X 
 


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Screening  
PART 1 
Double-blind Placebo-controlled 
PART 2 
Double-blind Active Treatment 
PART 3 
OSFU 
Week  
  
0 
(Baseline) 
4 
 
8 
12 
16a 
20 
24 
28b 
32 
36 
40 
44 
52c 
EoT 
72 
EoS 
Visit Number  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
Day  
Within 28 
Days 
1 
+/- 
3 days 
+/- 
3 days 
+/- 
3 days 
+/- 
3 days 
+/- 
3 days 
+/- 
3 days 
+/- 
3 days 
+/- 
3 days 
+/- 
7 days
+/- 
7 days 
+/- 
7 days 
+/- 
7 days 
+/- 
7 days 
CGIC 
 
 
 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
DLQI and NAPPA-QoL 
 
X 
 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
PGIS 
X 
X 
 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
PGIS-P 
X 
X 
 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
PGIC 
 
 
 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
PGIC-P 
 
 
 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
Abbreviations:  AE=Adverse event, BSA = body surface area; CGIC = Clinician Global Impression of Change; CGIS = Clinician Global Impression of 
Severity; C-SSRS = Columbia-Suicide Severity Rating Scale; DLQI = Dermatology Life Quality Index; ECG = electrocardiogram; EoT = End of Treatment; 
EoS = End of Study; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IWRS = Interactive Web 
Response System; mNAPSI=modified Nail Psoriasis Severity Index; NAPPA-QoL = Nail Assessment in Psoriasis and Psoriatic Arthritis Quality of Life; 
NAPSI = Nail Psoriasis Severity Index; NRS = Numeric Rating Scale; OSFU = Observational Safety Follow-up; PASI = Psoriasis Area and Severity Index;  
PGA-S = Physician Global Assessment-Skin; PGIC = Patient Global Impression of Change; PGIC-P = Patient Global Impression of Change for pain; PGIS = 
Patient Global Impression of Severity; PGIS-P = Patient Global Impression of Severity for pain; SC = subcutaneous; TB = tuberculosis; SC = subcutaneous; s-
TB = tuberculosis; ViSENPsO= Visual Medical Scale to Evaluate Nail Psoriasis Severity; TEAE = Treatment-
emergent Adverse Event  
a. 
Subjects who experience significant worsening of plaque psoriasis at Week 16 (defined as an increase 
-PGA] 
by at least 2 from the baseline measurement) will be eligible for an early escape.  
b. Subjects initially randomized to the placebo arm will begin tildrakizumab subcutaneous (SC) treatment at Week 28 for Part 2 of the study.  
c. Subjects who withdraw from the study will undergo the assessment corresponding to the last assessment of the study part from which they are leaving.  
Week 52 assessments (EoT) should be conducted approximately 4 weeks after administration of the last dose of study treatment.  
d. Perform a check that all inclusion/exclusion criteria remain satisfied at Baseline, including those related to results from tests performed at the Screening 
visit.   
e. Height and weight only.  
f. 
Adverse events reported prior to initiation of study treatment (Day 1) are to be recorded as non-TEAE.  
g. Chest X-ray is required only if a subject has positive or 2 indefinite QuantiFERON results.  
h. Any subject who is started on prophylactic treatment for latent TB during the Screening Period may be randomized 4 weeks after initiation of treatment 
without the need for rescreening.  
i. 
Following completion of Baseline assessments and confirmation that all inclusion/exclusion criteria have been met.  


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l 
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j. 
All study procedures of Baseline should be completed prior to study treatment administration. Following randomization, study treatment administration 
will begin on Day 1 of Week 0, Week 4, Week 16, and Week 28. At Week 28, subjects initially randomized to placebo will be switched over to receive 
tildrakizumab 100 mg at Weeks 28, 32, and 44. Subjects initially randomized to tildrakizumab 100 mg will continue to receive the active drug at Weeks 
28, 40, and 52. In order to maintain blind, subjects who were initially randomized to placebo will receive matching placebo injections at Weeks 40 and 
52, while subjects who were initially randomized to tildrakizumab will receive matching placebo injections at Weeks 32 and 44. Study treatment will be 
administered after performing all study-specific procedures for a particular visit.  
k. Blood samples are to be collected (pre-SC dose where applicable), after ECG and vital signs measurements. At visits where lipids are to be assessed, the 
blood samples are to be collected (pre-SC dose where applicable) after at least 12 hours fasting, following ECG and vital signs measurements. The 
following parameters will be reported at Screening only: Serum pregnancy, hepatitis B, hepatitis C, and HIV.  
l. 
Subjects with fungal nail infection whose fungal culture will be sent to the laboratory would have a Screening Period of 6 weeks.  
m. Urine pregnancy tests will be performed at the study center using materials supplied by the central laboratory.  
n. The subjects will be assessed for suicidal ideation and behavior at Screening using Screening C-SSRS, at Baseline, using Baseline C-SSRS, and each 
subsequent visit using the C-SSRS Since Last Visit version as specified in SoA.  
o. The efficacy assessments, ViSENPsO, NAPSI, mNAPSI, PGA-S, BSA, and PASI will be assessed at each visit during the study, starting at the 
Screening visit. Nail pain NRS will be based on the average score from 7-daily records at Baseline (if average of at least 4 out of the 7 daily recall 
observations in the week prior to baseline) and single-day recording at Screening.  
At all visits where efficacy assessments are made, the PROs (in particular nail pain NRS, PGIS, PGIS-P, PGIC, PGIC-P, C-SSRS, and QoL 
questionnaires) must be completed by the subject prior to efficacy assessments performed by the Investigator or designee. The order of the efficacy 
assessments evaluated by the Investigator should be the global assessments (e.g. ViSENPsO, s-PGA, PGA-S, CGIC and CGIS) followed by other 
efficacy assessments (e.g., mNAPSI, NAPSI, BSA and PASI). 
p. For a subset of n=50 subjects, the ViSENPsO will be administered to the same patient by two internal experts to assess inter-rater reliability at the 
Baseline and at EoT visits. The subset at EoT need not be the same set of subjects who had these assessments at baseline.  
q.  s-PGA criteria will be applicable for assessing eligibility and early escape at week 16 and week 28. 
 


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2.0 
INTRODUCTION  
2.1 
Background  
Psoriasis is a chronic inflammatory skin disorder and affects approximately 1% to 2% of people 
worldwide, with approximately 25% of subjects suffering from moderate to severe chronic 
plaque psoriasis. Plaque psoriasis, the most common form, affects 80% to 90% of patients. Nail 
psoriasis occurs in approximately 50% of patients with plaque psoriasis and is associated with 
pain and discomfort, causing a significant burden to quality of life (QoL) and work function (1). 
Nail psoriasis affects the nail matrix and the nail bed. The clinical manifestations of psoriasis of 
the nail matrix include pitting (most common lesion), nail plate crumbling, and leukonychia, 
while clinical manifestations of psoriasis of the nail bed include the presence of oil-drop or 
salmon patch dyschromia, onycholysis, subungual hyperkeratosis and splinter hemorrhages (2). 
Treatment includes topical agents, phototherapy, and/or systemic agents (conventional agents 
and biological treatments) (3, 4).  
2.2 
Study Rationale  
Biological therapies are indicated for the treatment of subjects with moderate to severe chronic 
plaque psoriasis who are candidates for phototherapy or systemic therapy. Currently approved 
biological treatments for moderate to severe plaque psoriasis include tumor necrosis factor 
(TNF) antagonist agents, i.e., etanercept (Enbrel®), infliximab (Remicade®), and adalimumab 
(Humira®), and the p40 (IL-12 and IL-23) antagonist ustekinumab (Stelara®). Despite the 
availability of treatment options for plaque psoriasis, nail lesions remain difficult to treat. The 
use of topical therapy, typically the first line of treatment for plaque psoriasis, is often 
challenging because of the poor diffusion into the nail tissue (1, 5). Patient satisfaction and 
compliance with topical therapy are known to be low (6). Thus, there remains an unmet need for 
effective therapeutic options for nail psoriasis.  
In recent years, accumulating data have implicated the IL-23/Th17 pathway in psoriasis 
pathogenesis. Recent genome-wide association studies have identified psoriasis risk alleles 
around gene regions that encode IL-23 (IL23A, IL12B) and the IL-23 receptor (IL-23R) (7, 8). 
Both p19 and p40 sub-units of IL-23 are over-expressed in psoriatic skin lesions, while the 
unique p35 sub-unit of IL-12 is not (9). Th17 cells, and the cytokines they elaborate, are 
abundant in psoriasis lesions, where they exert pro-inflammatory and pro-acanthotic effects (10, 
11). Compelling evidence for the functional role of IL-23p19 in psoriasis is demonstrated by a 
xenotransplant mouse model of psoriasis using AGR-129 mice wherein the administration of 
anti-human IL-23p19 inhibited the development of psoriatic lesions comparable to anti-TNF-  
blockers, the current benchmark in psoriasis treatment (12). It has been shown that disease 
improvement with anti-TNF- therapy correlated with the rapid down-modulation of IL-23 and 
Th17 cell products, and successful response to treatment was dependent on the inactivation of 
the IL-23/Th17 pathway (13, 14). Thus, while the use of IL-12/IL-23 p40 antagonists (e.g., 
ustekinumab and briakinumab) have been clinically validated in psoriasis (15-18), recent data 
suggest that the efficacy of these antagonists likely depends primarily, if not exclusively, on their 


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ability to neutralize IL-23 rather than IL-12 (8, 19, 20). This provides the rationale for selectively 
targeting IL-23p19 in subjects with nail psoriasis.  
Tildrakizumab is a high affinity (297 pM), humanized IgG1/  antibody that specifically binds to 
IL-23p19 (SN 08197) but does not bind human IL-12 (IL-12p40 and p35 heterodimer) or human 
p40. Tildrakizumab 100 mg by subcutaneous (SC) injection has recently been approved by the 
Food and Drug Administration for the treatment of moderate to severe chronic plaque psoriasis. 
Detailed information regarding the safety/tolerability of tildrakizumab can be found in the 
(21).  
Some special populations of patients will not be included in this study, such as those with 
hepatic, renal, and blood abnormalities, as well as infections, malignancy, myocardiopathy, and 
psychiatric disorders. Once we are evaluating a biological product to treat a nail condition, and 
based on the intrinsic characteristic of side effects that are generally observed in the class of 
biological products, we believe that these clinical conditions do not warrant the risk of 
generating or aggravating any of these clinical conditions, based on the following data: 
 Liver function test elevations have been reported with the use of tumor necrosis factor 
inhibitors (TNF-I) in patients with rheumatoid arthritis receiving adalimumab, etanercept, 
or infliximab (22). The overall incidence of liver function test elevations >1x ULN with 
TNF-I use was uncommon, and abnormalities >2x ULN were rarely observed. Significant 
differences were most consistently observed with infliximab, less commonly with 
adalimumab, and were not observed with etanercept compared with comparator disease-
modifying antirheumatic agents (DMARDs) (23).  
 It is already described in the literature cases of vasculitis developed in association with 
the use of tumor necrosis factor-  (TNF-
-vessel 
vasculitis was the most common finding, but systemic vasculitis, including peripheral 
nerve and renal vasculitis, was also frequently observed. (23, 24)  
 Cases of drug-induced hemolytic anemia after treatment with infliximab and adalimumab 
for treating ulcerative colitis and psoriasis, respectively, were described. (25, 26) 
 An observational cohort study was conducted using medical and outpatient pharmacy 
claims from 2 large US health insurance claims databases from January 1, 2003, through 
September 30, 2015. The databases included 31,595 patients in the Optum Clinformatics 
Data Mart and 76,112 patients in Truven MarketScan who were new users of acitretin, 
adalimumab, apremilast, etanercept, infliximab, methotrexate, and ustekinumab. The 
pooled PS-matched analysis yielded a decreased rate of overall serious infection in users 
of apremilast (hazard ratio [HR], 0.50; 95% CI, 0.26-0.94), etanercept (HR, 0.75; 95% 
CI, 0.61-0.93), and ustekinumab (HR, 0.65; 95% CI, 0.47-0.89) compared with 
methotrexate. We did not find a different rate of overall serious infection among users of 
acitretin, adalimumab, and infliximab compared with methotrexate. (27) 


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 There is little research on the use of biologic treatment in psoriasis patients with a history 
of established malignancy (28). The existing evidence is not in all cases sufficient in 
order to provide adequate insight into the management of these complex situations (29); 
however, positive associations between cutaneous squamous cell carcinomas and certain 
therapies have been found, and there is conflicting evidence regarding the risk of 
lymphoma and melanoma. Further studies are needed to determine the long-term safety 
of newer psoriasis treatments (interleukin [IL]-12/23, IL-17, Janus kinase 1/3, and 
phosphodiesterase-4 inhibitors), specifically their safety in patients with a history of 
cancer (30). 
 In a Korean, nationwide population-based prospective cohort study with a 15-year 
observational period. During the baseline period (1997-2000), total 1,773,786 Korean 
subjects who received health insurance from the National Health Insurance System were 
enrolled, and 5,788 subjects were defined as a psoriasis group. The number of new-
onset malignancies was collected during the observational period (2001-2015). Patients 
with psoriasis had a higher adjusted hazard ratio (aHR) for the development of 
overall malignancy (aHR 1.08, 95% confidence interval [CI] 1.00-1.18) and gastric 
cancer (aHR 1.31, 95% CI 1.08-1.58) compared to controls. The risks of non-Hodgkin 
lymphoma and non-melanoma skin cancer were significantly increased only in patients 
with psoriasis who received systemic treatments (aHR 2.86, 95% CI 1.07-7.61 and aHR 
3.93, 95% CI 1.47-10.47, respectively) (31). 
 Severe dilated cardiomyopathy induced by adalimumab and ustekinumab (32). 
Cardiac tamponade related to infliximab induction therapy was described, likely due to a 
type 3 hypersensitivity immune-complex reaction resulting in a reactive pericardial 
effusion (33). However, major cardiovascular events with tildrakizumab is considered 
low (34). 
 Patients with psoriasis have an increased risk of psychiatric comorbidities, suicidal 
ideation, and long-term course of the disease compared with patients who have other 
dermatological conditions (35, 36). However, concerns have been raised regarding the 
potential link between interleukin-17R blockade in the treatment of psoriasis and suicide, 
even if the current literature provides no evidence to support this association (36). 
This study is planned to be a multicenter, randomized, double-blind, placebo-controlled study to 
evaluate the efficacy and safety of the approved dose of tildrakizumab (100 mg by SC injection) 
in the treatment of moderate to severe nail psoriasis.   
2.3 
Benefit/Risk Assessment  
Details about specific benefits and risks for subjects in this clinical study can be found in the 
Investigator Brochure (IB) and the informed consent form (ICF).  
Given that efficacy benefits were reported in the completed Phase 2b study (Protocol P05495) 
and Phase 3 studies (P010 and P011) in plaque psoriasis, there is an expectation that subjects 


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treated with tildrakizumab will demonstrate improvement in nail psoriasis disease activity and 
Quality of life at Week 28. The study design allows early identification of subjects who have 
worsening of psoriasis at Week 16 and Week 28 and will be discontinued from treatment.   
The study has also been designed to minimize potential risks to subjects; all subjects will 
undergo screening procedures aimed at reducing the likelihood and impact of any such risks. In 
addition, regular safety monitoring during the treatment period for all subjects will ensure that 
any unanticipated effects of study participation are identified promptly and managed 
appropriately. Given the long half-life (T1/2) of tildrakizumab at doses previously studied, subjects 
will continue to be monitored throughout a 20-week wash-out period following the EoT visit, 
during which no active study treatment will be administered.  
This study will be performed in compliance with the protocol, the International Council for 
Harmonisation (ICH), Good Clinical Practice (GCP), and applicable regulatory requirements.   
 
 
 
 
 


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3.0 
OBJECTIVES AND ENDPOINTS  
Table 2: 
Study Objectives and Endpoints  
OBJECTIVES 
ENDPOINTS 
PRIMARY EFFICACY OBJECTIVE 
PRIMARY EFFICACY ENDPOINT 
To assess the efficacy of tildrakizumab in subjects 
with moderate to severe nail psoriasis, as measured 
by the proportion of subjects who achieve at least a 
75% improvement from baseline in total-modified 
Nail Psoriasis Severity Index (mNAPSI) at Week 
28.  
The proportion of subjects who achieve at least a 
75% improvement from baseline in total-
mNAPSI at Week 28. 
SECONDARY OBJECTIVES 
SECONDARY ENDPOINTS 
 
To assess the efficacy of tildrakizumab in the 
treatment of moderate to severe nail psoriasis 
compared with placebo as measured by 
ViSENPsO at Week 28. (Key secondary 
objective) 
 
- 
 
and at least a 2-point decrease from baseline 
at Week 28 as measured by the ViSENPsO. 
(Key secondary endpoint) 
 
To assess the effect of tildrakizumab on nail 
pain compared with placebo as measured by nail 
pain numeric rating scale (NRS) score at Week 
28.  
 
The proportion of subjects with at least 3 
point decrease from baseline in Nail Pain 
NRS score at Week 28 in subjects with 
baseline nail pain NRS score of > 3* 
 
To assess the effect of tildrakizumab on nail 
pain compared with placebo as measured by nail 
pain numeric rating scale (NRS) score at Week 
28.
 
Change in patient-reported nail pain NRS 
score from Baseline at Week 28.   
 
To assess the efficacy of tildrakizumab in the 
treatment of moderate to severe nail psoriasis 
compared with placebo as measured by 
mNAPSI, NAPSI, and ViSENPsO at Week 28.  
 
The proportion of subjects achieving total-
fingernail mNAPSI 90, mNAPSI 100, 
NAPSI 75, NAPSI 90, and NAPSI 100 at 
Week 28.  
 
Change in total-fingernail mNAPSI score 
from baseline at Week 28.  
 
Change in total-fingernail NAPSI score 
from baseline at Week 28. 
 
To assess the efficacy of tildrakizumab in the 
treatment of plaque psoriasis compared with 
placebo, as measured by Psoriasis Area and 
Severity Index (PASI), Phys
Assessment-Skin (PGA-S) score and body 
surface area (BSA) involvement at Week 28.  
 
The proportion of subjects achieving PASI 
75, PASI 90, and PASI 100 at Week 28.  
 
The proportion of subjects achieving a 
PGA-
with at least 2-point reduction from baseline 
to Week 28.  
 
Percentage change in total BSA involvement 
from baseline to Week 28. 


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OBJECTIVES 
ENDPOINTS 
 
To assess the effect of tildrakizumab on nail 
pain compared with placebo as measured by nail 
pain NRS score improvement at Week 28.  
 
The proportion of subjects with at least a 
30% decrease in Nail Pain NRS score from 
Baseline at Week 28 in subjects with a 
baseline nail pain NRS score of > 3*.   
 
EXPLORATORY OBJECTIVES 
EXPLORATORY ENDPOINTS 
 
To assess the effect of tildrakizumab over time 
at measured time points through Week 52 as 
measured by mNAPSI, NAPSI, Nail Pain NRS, 
BSA, PGA-S, 
Assessment (s-PGA), PASI, 
  
 
Change from Baseline in mNAPSI, NAPSI, 
Nail Pain NRS, BSA, PGA-S, s--PGA, 
PASI, 
 
 
  
 
To assess the effect of tildrakizumab on Quality 
of Life (QoL) as measured by:  
o Dermatology Life Quality Index (DLQI) and 
o Nail Assessment in Psoriasis and Psoriatic 
Arthritis QoL (NAPPA- QoL).  
 
Change from Baseline in DLQI score (total 
and 6 domain scores) and NAPPA-QoL 
score at measured time points through Week 
52.  
 
To assess the effect of tildrakizumab measured 
by using anchor scales: 
o Clinician Global Impression of Change 
(CGIC) 
o Clinician Global Impression of Severity 
(CGIS) 
o Patient Global Impression of Change 
(PGIC). 
o Patient Global Impression of Severity 
(PGIS). 
o Patient Global Impression of Severity for 
pain (PGIS-P). 
o Patient Global Impression of Change for 
pain (PGIC-P). 
 
Change from Baseline in CGIC, CGIS, 
PGIC, PGIC-P, PGIS, and PGIS-P at 
measured time points through Week 52. 
SAFETY OBJECTIVE
SAFETY ENDPOINT
To assess the safety and tolerability of 
tildrakizumab in subjects with moderate to 
severe nail psoriasis over 52 weeks. 
 
The percentage of subjects with incidence, 
seriousness, and severity of all adverse 
events.  
 
The percentage of subjects with severe 
infections defined as any infection meeting 
the regulatory definition of a serious adverse 
event (SAE), or any infection requiring 
intravenous (IV) antibiotics, whether or not 
reported as a serious event as per the 
regulatory definition.  
 
The percentage of subjects with 
malignancies (excluding carcinoma in situ 
of the cervix).  
 
The percentage of subjects with non-
melanoma skin cancer. 


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The percentage of subjects with melanoma 
skin cancer.  
 
The percentage of subjects with MACE.  
 
The percentage of subjects with study 
treatment-related hypersensitivity reactions 
(e.g., anaphylaxis, urticaria, angioedema, 
etc.).  
The percentage of subjects with injection 
site reactions (e.g. pain, erythema, edema 
etc.).  
*
be based on the average score from 7-daily records at Baseline. 
 
 
 


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4.0 
STUDY DESIGN  
4.1 
Overall Design  
This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy 
and safety of tildrakizumab in the treatment of moderate to severe psoriasis of the nails. The 
study will be conducted in up to approximately 35 study centers globally. The study duration per 
subject will be approximately 18 to 19 months, including a treatment duration of 52 weeks, and 
the total study duration will be approximately 3 years. The study design is presented in Figure 1.  
Approximately 96 eligible subjects (approximately 48 per arm) with moderate to severe plaque 
psoriasis and concomitant moderate to severe nail psoriasis will be randomized into the study. 
Eligible subjects will be randomized to one of the 2 arms in a 1:1 ratio: Arm A: Tildrakizumab 
100 mg, SC (n = 48) and Arm B: Placebo, SC (n = 48). The number of subjects with prior use of 
TNF-alpha inhibitors will be capped at 40%, and the analysis will be stratified based on prior use 
of these biologics. The randomization (1:1) to tildrakizumab and placebo will be stratified by 2 
factors: prior use of TNF-
kg).  
In a clinical trial with moderate-to-severe-plaque-psoriasis subjects, guselkumab was compared 
to adalimumab (VOYAGE 1, NCT02207231). One of the endpoints was nail disease. In that 
American population, about 20.9% of the subjects had experienced the use of biologic agents 
before joining the trial (37). In another trial, a 32-week study of secukinumab in subjects with 
nail psoriasis, performed in Germany, Australia, the Czech Republic, the USA, China, and 
Switzerland, 23.3% of the subjects had had previous exposure to a biological systemic psoriasis 
therapy (38). Based on these two recent manuscripts, the experience of the prior use of biological 
products in psoriasis ranges between 20% through 23.3%. To avoid excessive variability among 
the clinical sites, which could represent an issue and generate data not compatible with the 
population at large, it was decided to assume a conservative cap at 40% for this study. 
The study will comprise 3 parts:   
4.1.1 
PART 1: Double-blind Placebo-controlled (Day 1 to Week 28)  
After a Screening Period of up to 28 days and on Day 1, all eligible subjects will be randomized  
1:1 to receive either tildrakizumab 100 mg or placebo administered by SC injection on Week 0 
(Day 1), Week 4, and Week 16. Subjects should receive the first dose of study treatment within 
24 hours of randomization. The treatment period for the double-blind, placebo-controlled part of 
the study is 28 weeks.  
Early Escape: At Week 16, subjects who experience significant worsening of plaque psoriasis 
(defined as an increase in s-PGA by at least 2 from the baseline measurement) will be eligible for 
an early escape. (Appendix 20) Subjects selected for early escape by the Principal Investigator at 
Week 16 will have study medication discontinued and will complete the End of Treatment visit 


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assessment, followed by the observational safety follow-up period. Subjects entering early 
escape may be replaced so as to meet the planned evaluable sample size goal for the primary 
endpoint analysis. 
An interim analysis may be performed that could include an unblinded sample size re-estimation 
(SSRE). The sample size of the study could be increased as a result of this SSRE. In the event of 
an increase in sample size, the total sample size of the study will not exceed a total of 
approximately 282 randomized subjects. 
4.1.2 
PART 2: Double-blind Active Treatment Extension (Week 28 to Week 52)  
At Week 28, subjects initially randomized to placebo will be switched over to receive 
tildrakizumab 100 mg at Weeks 28, 32, and 44. Subjects initially randomized to tildrakizumab 
100 mg will continue to receive tildrakizumab at Weeks 28, 40, and 52. In order to maintain the 
blind, subjects in both treatment arms will receive matching placebo injections at specified time 
points as described in the SoA.  
Subjects who experience significant worsening of plaque psoriasis at Week 28 (defined as an 
increase in s-PGA by, at least 2 from the baseline measurement) will be discontinued from 
treatment. Subjects who do not fulfill this criterion at Week 28 will continue to receive 
tildrakizumab in Part 2, as described above.  
4.1.3 
PART 3: Observational Safety Follow-up (Week 52 to Week 72)  
After Week 52 (or early termination of study treatment prior to Week 52), the study treatment 
should be stopped and all subjects, including those who terminated early from Part 1 and, 2 will 
enter the 20-week Observational Safety Follow-up period to monitor safety and tolerability for 
20 weeks following the last dose of study treatment. During the follow-up period, subjects 
should continue on study-approved concomitant medications only, however, may be placed on 
appropriate therapies for safety concerns or significant worsening of psoriasis based on the 
judgment of the Investigator. The subjects will not receive study treatment during the follow-up 
period.  
The study may have a primary analysis, which will be performed when the last subject has 
completed the Week 28 visit, and a final analysis to be performed when the last subject has 
completed the study.  
Subjects who withdraw from the study will undergo the assessment that corresponds to the last 
assessment of the study part from which they are leaving. Subjects discontinued from study 
treatment at any time (apart from the withdrawal of informed consent) will complete the EoT 
(Week 52) assessment approximately 4 weeks after the last dose of study treatment and enter the 
20-week observational safety follow-up. Subjects who withdraw from the study during Part 3 
will undergo the Week 72 (End of Study [EoS]) assessments approximately 4 weeks after their 
last visit.  


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4.2 
Scientific Rationale for Study Design  
This is a randomized, double-blind, placebo-controlled, Phase 3 study to evaluate the efficacy 
and safety of tildrakizumab administered by SC injection in subjects with moderate to severe nail 
psoriasis. The study has been developed based on design features used in the completed Phase 2b 
protocol for subjects with psoriasis as well as ongoing Phase 3 studies for subjects with plaque 
psoriasis. In this study, tildrakizumab will be compared with a placebo. Placebo-controlled 
studies are the best way to ensure the accurate assessment (in absolute terms) of the safety and 
tolerability of a new molecular entity.   
The study has been designed with 4 distinct phases (Screening, Double-blind Placebo-controlled 
period, Double-blind active treatment period, and an Observational safety follow-up period).  
This enables scientific evaluation of efficacy at Week 28. The 52-week treatment duration is 
expected to provide adequate time to assess the safety and efficacy of tildrakizumab in subjects 
with nail psoriasis.  
4.3 
Justification for Dose  
The dose of tildrakizumab was selected based on the results of Phase 2 dose-ranging study, 
P05495, and two Phase 3 studies (P010 and P011), in addition to an exposure-response model 
that was developed using these results.  
In P05495, 4 treatment regimens of tildrakizumab were compared with a placebo (5, 25, 100, and 
200 mg SC, administered at Weeks 0 and 4 and then every 12 weeks until Week 52). Unbalanced 
randomization was used to define dose-response relationships and to support the re-
randomization of subjects in 2 treatment arms during the maintenance phase of the study (Part 2). 
At Week 16, Psoriasis Area and Severity Index (PASI) 75 response rates (primary endpoint) 
were 33% in the 5 mg arm, 64% in the 25 mg arm, 66% in the 100 mg arm, 74% in the 200 mg 
arm, and 4% in the placebo arm. The difference between each active dose versus placebo in 
was 33% in the 5 mg arm, 58% in the 
25 mg arm, 62% in the 100 mg arm, 74% in the 200 mg arm and 2% in the placebo arm. The 
difference between each active dose versus placebo in terms of PGA response was statistically 
 response over the range of doses 
studied: the 5 and 25 mg doses demonstrated suboptimal efficacy for the PASI 75 and PGA 
endpoints, the 100 mg dose demonstrated near-maximal efficacy and the 200 mg dose appeared 
to show maximal efficacy.  
The results from the Phase 2 (P05495) dose-ranging study were then used to develop an 
exposure-response model to analyze PASI 75 and PASI 90 response rates. The model-based 
analysis of the clinical data from P05495 suggested that the 100 mg dose was near the plateau of 
the exposure-response relationship for PASI 75. The incremental benefit for 200 mg versus 100 
mg was estimated to be ~2% for PASI 75 response and 2% to 6% for PASI 90 response.  


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These findings were confirmed in two Phase 3 studies (P010 and P011) that further demonstrated 
that tildrakizumab 200 mg and 100 mg were efficacious and were well tolerated in the treatment 
of patients with moderate to severe chronic plaque psoriasis. The results for the primary and 
secondary endpoints in these studies were similar for tildrakizumab 200 mg and 100 mg. The 
results of the pivotal Phase 3 studies were the basis for the approval of tildrakizumab 100 mg in 
the United States on 20 March 2018 for the treatment of adults with moderate to severe plaque 
psoriasis who are candidates for systemic therapy or phototherapy, and in Australia on 06 
September 2018 for the treatment of adults with moderate to severe plaque psoriasis who are 
candidates for systemic therapy.  
In considering both clinical data and the model-based analysis, this Phase 3b study will include 
only a 100 mg dose. The safety/tolerability profile of tildrakizumab to date supports this 
approach.  
4.4 
End of Study Definition  
A subject is considered to have completed the study if he/she has completed all parts of the 
study, including the last visit Week 72 (EoS).  
The EoS is defined as the date of the last visit of the last subject in the study globally.  


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5.0 
 STUDY POPULATION  
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.  
5.1 
Inclusion Criteria  
Subjects are eligible to be included in the study only if all of the following criteria apply:  
1. Subjects should be 18 years or older at the time of signing the informed consent during the 
Screening visit.  
2. Subjects with a chronic moderate to severe plaque-type psoriasis for at least 6 months (as 
determined by subject interview and confirmation of diagnosis through physical 
examination by Investigator).  
3. Subjects must have moderate to severe nail psoriasis at Screening and Baseline, defined by:  
 mNAPSI s
 
 ViSENPsO 3 
4. Subjects must have moderate to severe plaque psoriasis at Screening and Baseline, defined 
by:  
 s-PGA score of at least 3. 
 
 
 
 
5. Subjects must be considered candidates for systemic therapy, meaning psoriasis 
inadequately controlled by topical treatments (corticosteroids), and/or phototherapy, and/or 
previous systemic therapy.  
6. Subjects have a negative evaluation for tuberculosis (TB) within 4 weeks before initiating 
study treatment, defined as a negative QuantiFERON® test. Subjects with a positive or 2 
successive indeterminate QuantiFERON® tests are allowed if they have all of the following:  
 No history of active TB or symptoms of TB  
 A posteroanterior (PA) chest radiogram (with associated report available at study 
center) performed within 3 months of Screening with no evidence of active TB (or of 
any other pulmonary infectious diseases)  
 If prior latent TB infection (LTBI), must have a history of adequate prophylaxis (per 
local standard of care)  
 If the presence of LTBI is established, then treatment according to local country 
guidelines must have been followed for 4 weeks prior to inclusion in the study. A 
maximum of 2 QuantiFERON® tests are allowed. A re-test is only permitted if the 
first is indeterminate; the result of the second test will then be used.  


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7. 
questions:  
 Subject is a male  
 Subject is a female and agrees to abstain from heterosexual activity OR use a highly 
effective method of contraception as per  Appendix 5. 
 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)  
 Subject is a surgically sterilized female or is documented to be postmenopausal. For 
contraceptive guidance, see Appendix 5. 
8. For women of childbearing potential, a negative serum pregnancy test at Screening and a 
negative urine pregnancy test within 24 hours prior to Day 1 and on subsequent visits at 
which study treatment doses are scheduled.  
9. Subjects must have results of a physical examination within normal limits or clinically 
acceptable limits to the Investigator prior to Day 1. The Investigator is encouraged to 
consult with the Medical Monitor (or appropriate designee) if there are questions regarding 
the significance of any out-of-range values.  
10. Subjects must be capable of giving signed informed consent as described in Appendix 1, 
which includes compliance with the requirements and restrictions listed in the ICF and this 
protocol.  
5.2 
Exclusion Criteria   
Subjects are excluded from the study if any of the following criteria apply:  
1. Subjects who have laboratory abnormalities at Screening, including any of the following:  
 
 upper 
limit of normal (ULN). 
 
 
 
 
 White blood cell count <3.0 × 103
 
 Any other laboratory abnormality which, in the opinion of the Investigator, will prevent 
the subject from completing the study or will interfere with the interpretation of the study 
results.  
2. Subjects who have predominantly non-plaque forms of psoriasis, specifically erythrodermic 
psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated 
psoriasis, or new-onset guttate psoriasis.  


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3. Subjects with ongoing inflammatory skin diseases other than psoriasis or any other disease 
affecting the fingernails, which may potentially confound the evaluation of the study 
treatment.  
4. Subjects with fungal nail infection should be excluded from the study. Subjects in whom the 
Investigator suspects a fungal nail infection* (see Appendix 6) in addition to nail psoriasis 
should have scrapings sent for direct microscopy and fungal culture. If fungal culture or 
direct microscopy of nail scrapings turns out to be positive for fungal infection, the subject 
should be excluded from the study. At the discretion of the investigator, Periodic Acid-
Schiff (PAS) staining for nail clippings could also be considered to rule out fungal infection 
of the nails. Direct microscopy or fungal culture is not required if fungal infection is 
diagnosed in PAS staining.   
*Subjects with fungal nail infection whose fungal culture will be sent to the laboratory 
would have a Screening Period of 6 weeks.   
5. Women of childbearing potential who are pregnant, intend to become pregnant (within 6 
months of completing the study), or are lactating.  
6. Subjects with any infection or history of recurrent infection requiring treatment with 
systemic antibiotics within 2 weeks prior to screening or severe infection (e.g., pneumonia, 
cellulitis, bone or joint infections) requiring hospitalization or treatment with intravenous 
(IV) antibiotics within 6 weeks prior to Screening.  
7. Subjects with any previous use of tildrakizumab or other IL-23/Th-17 pathway inhibitors, 
including p40, p19, and IL-17 antagonists for psoriasis.  
 Prior use of TNF-alpha inhibitors with a wash-out period of 12 weeks would be allowed. 
However, the number of subjects with prior use of TNF-alpha inhibitors would be capped 
at 40%, and the analysis will be stratified based on prior use of these biologics. 
8. Use of the medications listed below within the indicated washout period prior to Baseline 
visit: 
Excluded Medications/treatments 
Wash-out period prior to randomization 
Topical psoriasis treatment (including medicated 
nail preparations) 
2 Weeks  
Conventional systemic psoriasis therapy (e.g. 
cyclosporine, methotrexate, acitretin, fumaric 
acid esters) or phototherapy (e.g. ultraviolet 
[UV] B light phototherapy, Psoralen-UVA 
(PUVA) therapy, tanning salon or home-
administered UVB) 
4 Weeks  
Treatment with injectable or oral corticosteroids; 
4 Weeks  
Treatment with a biological agent other than 
Tildrakizumab or any other IL-23/Th-17 
inhibitors, including p40, p19, or IL-17 
inhibitors 
12 Weeks (or 5 half-lives, whichever is 
longer)  
Treatment with an investigational agent  
4 Weeks (or 5 half-lives, whichever is 
longer) 
 


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9. Subjects with a positive human immunodeficiency virus test result, hepatitis B surface 
antigen, or hepatitis C virus test result. Subjects with Hepatitis C viral (HCV) antibody 
reactive test could be included if HCV-RNA is negative. 
10. Subjects with a prior malignancy or concurrent malignancy (excluding successfully treated 
basal cell carcinoma, squamous cell carcinoma of the skin in situ, squamous cell carcinoma 
of the skin with no evidence of recurrence within 5 years or carcinoma in situ of the cervix 
that has been adequately treated).  
11. Subjects who have received live viral or bacterial vaccination within 4 weeks prior to 
Baseline or who intend to receive live viral or bacterial vaccination during the study.  
12. Subjects who are currently participating in another interventional clinical study or have 
participated in an interventional clinical study within 5 half-lives (of the drug) to wash out 
prior to randomization. (Subjects participating in observational studies or non-interventional 
registry studies may be included in the study).  
13. Subject or family member is among the personnel of the study center or Sponsor/designee 
staff directly involved with this study.  
14. Subjects who have any concomitant medical condition, which in the opinion of the 
Investigator, could affect the study outcome or present an unacceptable risk.  
15. Subjects who were hospitalized due to an acute cardiovascular event (such as myocardial 
infarction, cerebrovascular accident, cardiovascular illness [e.g., angina pectoris], or 
cardiovascular surgery [such as coronary artery bypass]) within 6 months before Screening. 
16. Subjects who, in the opinion of the Investigator, will not be reliable participants in the study 
and those who can confound the results of the study.  
17. Subjects who have a history of alcohol or drug abuse in the previous year.  
18. Subjects who have a high risk of suicidality at the Screening assessment based on the 
12 months to Questions 4 or 5 in the suicidal ideation section or any positive response in the 
behavioral section of the C-SSRS.  
19. Subjects with any other clinically significant laboratory abnormality, which, in the opinion 
of the Investigator, will prevent the subject from completing the study or will interfere with 
the interpretation of the study results.  
20. Subjects with a known history of allergy or hypersensitivity to any of the inactive 
ingredients of the Tildrakizumab or placebo formulations.  
5.3 
Lifestyle Considerations  
Excessive exposure to sunlight should be avoided during the study. Subjects should avoid the 
use of tanning booths or other ultraviolet light sources for the duration of the study.   
5.4 
 Screen Failures  
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently entered in the study. A minimal set of screen failure information is required to 


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ensure transparent reporting of screen failure subjects to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities. 
The minimal information includes demography, screen failure details, eligibility criteria, and any 
SAE.  
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened at the discretion of the Investigator for up to 2 additional times, with a minimum of 2 
weeks between each rescreening. When a subject is rescreened, all Screening procedures will be 
repeated.    
Note: If the original ICF was signed within 30 days of the rescreening visit, a new ICF does not 
need to be completed.  
Rescreened subjects should not be assigned the same subject number as for the initial Screening. 
Any subject who is started on prophylactic treatment for latent TB during the Screening Period 
may be randomized 4 weeks after initiation of treatment without the need for rescreening.  Any 
subject with a negative fungal nail infection whose fungal culture was sent to the laboratory 
would have a Screening Period of 6 weeks 
 
 
 


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6.0 
STUDY TREATMENT  
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a subject according to the study protocol.  
The study treatment in this study is tildrakizumab and placebo. All subjects will be dosed at the 
same time points to maintain the blind throughout the study. The study arms will receive study 
treatment during the course of the study as follows:  
Arm A:   
o Tildrakizumab 100 mg SC injections at Weeks 0, 4, 16, 28, 40, and 52.  
o Placebo injections at Weeks 32 and 44.  
Arm B:   
o Placebo injections at Weeks 0, 4, 16, 40, and 52.  
o Tildrakizumab 100 mg SC injections at Weeks 28, 32, and 44.  
6.1 
Study Treatment Administered  
Study treatment details are provided in Table 3. 
Table 3: 
Study Treatment Details  
Study Treatment Name:  
Tildrakizumab  
Placebo  
Dosage Formulation:  
Tildrakizumab will be available as a 
prefilled syringe (PFS) with 100 mg of 
tildrakizumab and 1 mL solution. Each 
PFS will contain tildrakizumab solution 
and the following inactive ingredients: 
L-Histidine,  
L-Histidine Hydrochloride 
Monohydrate,  
Sucrose, and Polysorbate 80 
The placebo formulation is similar to 
the tildrakizumab without the active 
ingredient. It will be available in PFS 
containing 1 mL solution and the 
following inactive ingredients:  
L-Histidine, L-Histidine 
Hydrochloride Monohydrate, Sucrose, 
and Polysorbate 80.   
Unit Dose 
Strength/Dosage Level: 
100 mg  
-  
Route of Administration  
SC 
SC 
Dosing Instructions:  
All the subjects will be dosed at the same time points to maintain the study blinding
throughout the study.  
For SC injections, tildrakizumab/placebo is supplied in a ready-to-use 1 mL PFS 
with a safety device. Each PFS is assembled with a safety device to prevent 
accidental needle sticks.   
Subcutaneous injections should be rotated with each dose and should not be given 
into moles, scars, tattoos, or areas where the skin is tender, bruised, red, hard, or 
not intact.  
Abdominal administration is the preferred site for SC doses.  
Packaging and Labeling  
Tildrakizumab will be provided in PFS. 
Each PFS will be labeled as per country 
requirements.  
Placebo will be available in identical 
containers with the same excipients 
(with no active drug) 


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6.2 
Preparation/Handling/Storage/Accountability  
1) The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatments received, and any discrepancies are 
reported and resolved before the use of the study treatment.  
2) Only subjects enrolled in the study may receive study treatment, and only authorized study 
center staff may supply or administer the study treatment. All study treatments must be 
stored in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions, with access limited to the Investigator and 
authorized study center staff.  
3) The study treatment should be kept in a locked storage area under refrigerated storage at 2°C 
to 8°C. Study treatment experiencing temperature excursions outside this temperature should 
be quarantined and can only be released for subject use after consultation with the Sponsor.  
4) The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance (i.e., 
receipt, reconciliation, and final disposition records).  
5) Further guidance and information for the final disposition of unused study treatment will be 
provided by the study center monitor.   
The Investigator, a member of the study center staff, or a hospital pharmacist must maintain an 
adequate record of the receipt and distribution of all study treatments using the Drug 
Accountability Form.  
6.3 
Measures to Minimize Bias: Randomization and Blinding  
All subjects will be centrally assigned in a 1:1 ratio to receive either tildrakizumab 100 mg or a 
placebo using an Interactive Web Response System (IWRS). Before the study is initiated, the 
Login information and directions for the IWRS will be provided to each study center.  
This is a double-blind study with limited access to the randomization code. Tildrakizumab and 
placebo will be identical in physical appearance. The treatment each subject will receive will not 
be disclosed to the Investigator, study center staff, subject, Sponsor, or study vendors. The 
treatment codes will be held by the Clinical Supplies Department of the Sponsor or their 
designated Contract Research Organization (CRO).   
Study treatment will be dispensed at the study visits summarized in the SoA (see Section 1.3). 
All subjects will be dosed at the same time points to maintain the study blinding throughout the 
study. Returned study treatment should not be re-dispensed to the subjects.  


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6.4 
Study Treatment Compliance  
The prescribed dosage, timing, and mode of administration may not be changed. Any departures 
from the intended regimen must be recorded in the eCRFs.  
On Week 0 (Day 1), Weeks 4, 16, 28, 32, 40, 44, and 52 the study treatment will be administered 
at the study center by appropriately trained staff.  
Study treatment accountability and subject compliance will be documented throughout the 
treatment periods (Part 1 and Part 2) using study-specific study treatment dispensing record 
forms. If a subject does not receive the scheduled dose, every effort should be made to 
administer the dose as soon as possible.   
6.5 
Concomitant Therapy  
Any medication or vaccine (including over-the-counter [OTC] or prescription medicines, 
vitamins, and/or herbal supplements) that the subject is receiving at the time of enrollment or 
receives during the study must be recorded on the eCRF along with:  
 Reason for use.  
 Dates of administration, including start and end dates.  
 Dosage information, including dose and frequency.  
In addition, all prior medications used to treat the disease conditions and any other medications 
taken within 6 months prior to enrollment must be recorded in the eCRF.   
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy.  
A list of excluded medications/therapy is provided in Table 4. 


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Other concomitant medication may be considered on a case-by-case basis by the Investigator in 
consultation with the Medical Monitor if required.  
6.5.1 
Rescue Medicine  
Not applicable.  
6.5.2 
Allowed Concomitant Medication  
 Acetaminophen (paracetamol) may be used by the subject as needed except within 7 days 
before a scheduled study efficacy evaluation except EOS/week 72 visit, when nail pain 
will be recorded on the NRS scale.  
 Medications needed to treat pre-existing medical conditions that are not exclusionary to 
the study.  
 Medications necessary to treat adverse events (AEs) or medical emergencies.  
 
-hydroxy acids or keratolytic agents).  
 Medicated shampoos that do not contain corticosteroids.  
 Vitamins, supplements, antacids, and other over-the-counter medications that are not 
exclusionary to the study.  
 Class VI or VII low-potency topical corticosteroids (such as prednicarbate 0.05%, 
triamcinolone acetonide 0.025%, fluocinolone acetonide 0.01%, desonide 0.05%, 
hydrocortisone 2.5% or hydrocortisone 1%) are allowed in Part 2 of the study, but not in 
Part 1.  
Note that the use of any concomitant medication must relate to the documented medical history, 
prophylaxis, or an AE of the subject.  
6.6 
Dose Modification  
No dose modification is allowed in this study. Study treatment can be interrupted temporarily or 
permanently if dee
 
6.7 
Treatment after the End of the Study  
The Sponsor will not provide any study treatment to the subjects during the Observational Safety 
Follow-up period. Patient care should not differ from what is normally expected for subjects with 
psoriasis.  
6.8 
Excluded Medication 
Excluded medications/therapy is listed below. The concomitant use of an excluded 
medication/therapy with study treatment is not in compliance with the study protocol and must 
be recorded in the eCRF.  


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Table 4: 
Excluded Medications/treatments  
Topical psoriasis treatment (including medicated nail preparations) *   
Conventional systemic psoriasis therapy (e.g., cyclosporine, methotrexate, acitretin, fumaric 
acid esters) or phototherapy (e.g., ultraviolet [UV] B light phototherapy, Psoralen-UVA 
(PUVA) therapy, tanning salon or home-administered UVB)  
Treatment with injectable or oral corticosteroids;   
Treatment with a biological agent other than study treatment (including monoclonal antibodies, 
alefacept)  
Treatment with an investigational agent (other than study treatment)  
*Any class of topical corticosteroid is prohibited in the base study. Low-potency topical 
corticosteroids (class VI and VII) are only allowed during Part 2 of the study.   
 
  


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7.0 
DISCONTINUATION OF STUDY TREATMENT AND SUBJECT 
DISCONTINUATION/WITHDRAWAL   
7.1 
Discontinuation of Study Treatment  
Subjects may voluntarily discontinue study treatment for any reason at any time and enter the 20-
week wash-out period or completely withdraw from the study (see Section 7.2). Subjects who 
consent to enter the wash-out period will undergo the Week 52 (EoT) assessment at 
approximately 4 weeks after administration of the last dose of study treatment.  
At any time during Part 1 or Part 2 of the study, the Investigator should discontinue the study 
treatment of a given subject if, on balance, he/she believes that continuation would be 
-being.   
The study treatment must be discontinued under the following circumstances, and the further 
steps need to be discussed with the Medical Monitor:  
 An SAE, drug reaction or complication, or an unacceptable AE, whether attributed to 
study treatment or not, precludes the continuation of treatment with study treatment. This 
includes the development of allergic reactions or the development of other potentially 
serious drug reactions to medication required by the protocol.  
 Diagnosis of malignancy (except basal or squamous cell carcinoma of the skin) during 
the study (at the discretion of the subject and Investigator).  
 Meets early escape criteria at week 16 or week 28 
 Subjects who develop suicidal behavior.  
 Evidence of pregnancy.  
 Withdrawal of informed consent.  
 Lost to follow-up.  
 Significant non-compliance of the subject with study procedures.  
 Decision of the Sponsor to terminate the subject, study center, or the study.  
Subjects who discontinue the study treatment may not be replaced.   
Subjects who withdraw from the study will undergo the assessment that corresponds to the end 
assessment of the study part which they are leaving. Week 52 assessments (EoT) should be 
conducted approximately 4 weeks after administration of the last dose of study treatment.  
See the SoA (see Section 1.3) for data to be collected at the time of treatment discontinuation and 
follow-up and for any further evaluations that need to be completed.  
7.1.1 
Temporary Discontinuation   
Study treatment can be interrupted temporarily in case of:  


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


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The following actions must be taken if a subject fails to return to the study center for a required 
study visit:  
 The study center must attempt to contact the subject and reschedule the missed visit as 
soon as possible and counsel the subject on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the subject wishes to and/or should continue 
in the study.  
 Before a subject is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, if 
methods). These conta
 
 Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study.   
 


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8.0 
STUDY ASSESSMENTS AND PROCEDURES  
 Study procedures and their timing are summarized in the SoA (see Section 1.3).   
 Some visits may be performed virtually depending on circumstances at the study site and 
in the community upon discussion with the Sponsor. 
 Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the subject should continue or discontinue the 
study treatment.  
 Adherence to the study design requirements, including those specified in the SoA (see 
Section 1.3), is essential and required for the study's conduct.  
 All Screening evaluations must be completed and reviewed to confirm that potential 
subjects meet all eligibility criteria. The Investigator will maintain a Screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for 
screening failure, as applicable.   
 
count) and obtained before signing of the ICF may be utilized for Screening or Baseline 
purposes provided the procedures met the protocol-specified criteria and were performed 
within the time frame defined in the SoA (see Section 1.3).  
 The maximum amount of blood collected from each subject over the duration of the 
study, including any extra assessments that may be required, will not exceed more than 
150 mL. Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples.  
 The efficacy assessments ViSENPsO, NAPSI, mNAPSI, PGA-S, BSA, PASI, and nail 
pain NRS score will be assessed at each visit during the study. The visits where efficacy 
assessments are made, the Patient Reported Outcomes (PROs) (in particular the 
Dermatology Life Quality Index [DLQI],  Nail Assessment in Psoriasis and Psoriatic 
Arthritis Quality of Life [NAPPA-QoL], the nail pain NRS, Patient Global Impression of 
Change [PGIC], Patient Global Impression of Change for pain [PGIC-P], Patient Global 
Impression of Severity [PGIS], Patient Global Impression of Severity for pain [PGIS-P], 
and Columbia Suicidal Severity Rating Scale [C-SSRS]) must be completed by the 
subject prior to efficacy assessments performed by the Investigator (or designee). s-PGA, 
CGIS, CGIS will be assessed at visits as defined in the SoA.  
 The order of the efficacy assessments evaluated by the Investigator should be the global 
assessments (e.g., ViSENPsO, s-PGA, PGA-S, CGIC, and CGIS) followed by other 
efficacy assessments (e.g., mNAPSI, NAPSI, BSA, and PASI). 
  


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 To ensure consistency of efficacy assessments over the study duration, it is preferred that 
the same person/assessor perform the same assessment on the same subject across all 
visits.   
 All study treatments will be administered subcutaneously. All doses of study treatment 
will be administered at the study center; at home, administration is not permitted.   
 All unscheduled visits and assessments performed during the visits will be recorded in 
and concomitant medications as well as performing any assessments or collecting 
samples deemed necessary at the discretion of the Investigator.  
8.1 
Efficacy Assessments   
Efficacy assessments after Week 28 are considered exploratory. Time points for efficacy 
assessments are provided in the SoA (see Section 1.3).   
8.1.1 
Nail Psoriasis Severity Index (NAPSI) 
The Nail Psoriasis Severity Index (NAPSI) is a numeric, reproducible, objective, simple tool for 
the evaluation of nail psoriasis (see Appendix 7). This scale is used to evaluate the severity of 
nail bed psoriasis and nail matrix psoriasis by area of involvement in the nail unit. A modified 
version (mNAPSI) was developed to enhance the face validity and feasibility of this tool (see 
Appendix 8).   
The following items will be assessed:  
 Nail pitting  
 Nail onycholysis and oil-drop dyschromia  
 Nail crumbling  
 Nail leukonychia, splinter hemorrhages, hyperkeratosis, red spots in the lunula  


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A score is 0 if the items are not present, 1 if they are present in 1 quadrant of the nail, 2 if present 
in 2 quadrants of a nail, 3 if present in 3 quadrants of a nail, and 4 if present in 4 quadrants of a 
nail. Thus, each nail has a matrix score (0-4) and a nail bed score (0-4), and the total nail score is 
the sum of those 2 individual scores (0-8) sum of the total score of all involved fingernails is the 
total NAPSI score for that patient at that time point.   
Only the fingernails will be evaluated in this study.   
8.1.2 
ment of Skin - Whole body (PGA-S) 
A systematic review to evaluate the degree of correlation between two commonly 
used psoriasis assessment tools: The Psoriasis Area and Severity Index (PASI) and Physician 
Global Assessment (PGA). It was recorded and compared the percent of patients achieving both 
a 75% reduction in PASI score (PASI 75) and PGA 0 or 1 (clear or almost clear) at 8 to 16 
weeks, 17 to 24 weeks, and greater than 24 weeks of treatment with the investigational drug. 
Indeed, the two assessment tools correlate very tightly except at the lower bounds of therapeutic 
efficacy (39-41). The r(2) values for the correlation between PASI 75 and a score of clear or 
almost clear on the PGA were 0.9157 at 8 to 16 weeks and 0.892 at 17 to 24 weeks. Indeed, the 
two assessment tools are substantially redundant and either alone is a sufficient tool for 
assessing psoriasis severity in patients with moderate to severe disease (39). 
Plaque psoriasis will be assessed using a 6-
oint (see 
Appendix 9). The Investigator should select the category that best represents the condition of all 
the psoriasis lesions:  
0 = Cleared, except for residual discoloration  
1 =  Minimal - majority of lesions have individual scores for Thickness  
(T) + Erythema (E) + Scaling (S)/3 that averages 1,   
2 = Mild - majority of lesions have individual scores for T + E + S/3 that averages 2,   
3 = Moderate - majority of lesions have individual scores for T + E + S/3 that averages 3,   
4 = Marked - majority of lesions have individual scores for T + E + S/3 that averages 4, 
5 = Severe - majority of lesions have individual scores for T + E + S/3 that averages 5. 
8.1.3 
Psoriasis Area and Severity Index (PASI) 
Psoriasis Area and Severity Index will be used to determine the treatment response (PASI 75, 
PASI 90, and PASI 100) in subjects with nail psoriasis. The PASI includes scores on erythema, 
thickness, scaling, and percentage of BSA affected (see Appendix 10).  


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8.1.4 
Nail Pain Numeric Rating Scale (NRS) 
The NRS is a simple assessment tool that subjects will use to report the intensity of their pain 
during the study (see Appendix 11). An improvement of 30% in Nail Pain NRS score from 
 in nail 
psoriasis studies. (42) There are numerous precedents in pain measurement across conditions for 
 In this study, a decrease in absolute nail 
pain NRS score of at least 3 points will be assessed. 
 
how would you rate the worst nail pain you experienced during the previous 24 hours?  
Patients will complete pain assessments by responding at each Visit, on a scale of 0 to 10, with 0 
 
nail pain experienced during previous 24 hours, on each of the seven consecutive days leading up 
to the visit. However, at the Screening, pain NRS will be assessed once. The complete 
observation will be performed on the average score for each visit that will be based on the seven 
daily scores. The complete score at a given visit will be based on an average of no less than four 
of the seven prompted valid daily recall observations. 
 No imputation of missing daily recalls will be used, and the change in averaged scores at 
Baseline and Week 28 will provide the basis for analysis.  The analysis will be conducted with 
complete observations, to be detailed in the SAP. 
The subject should complete the nail pain NRS at the time points indicated in the SoA (see 
Section 1.3). Subjects will be instructed to record their nail pain NRS scores in the patient diary.  
Only the fingernails will be evaluated in this study.   
Acetominphen (allowed pain medication) cannot be taken for the 7 days when nail pain will be 
recorded on NRS scale.  
8.1.5 
Total Body Surface Area (BSA) 
The BSA will be used to measure the severity of overall psoriasis. It is defined as the percentage 
of the total BSA affected by psoriasis. The overall BSA affected by psoriasis will be measured at 
time points specified in the SoA (see Section 1.3). The BSA will be measured using the palm 
method where the palm of the 
represents 1% of the BSA. The affected areas are then calculated by their size compared to the 
 
8.1.6 
Visual Medical Scale to Evaluate Nail Psoriasis Severity (ViSENPsO) 
ViSENPsO is a new, simpler, and visual-based clinician-reported outcome (ClinRO) scale, 
assessing nail psoriasis severity. In addition to being used as the key secondary efficacy 
endpoint, the scale will promote well-defined and reliable evaluations of nail psoriasis treatment 


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outcomes in studies where a biological product is used; it will be validated in this study (see 
Appendix 12). 
8.1.7 
-PGA) 
An s-PGA has many variations, including 5, 6, or 7-p
-point scale to evaluate subjects meeting 
early escape conditions, as better explored in Appendix 20. 
This study will utilize s-PGA  to determine if there is worsening of disease that warrants the 
discontinuation of the subject from the study.  
8.1.8 
Clinician Global Impression of Change (CGIC) 
The Clinician Global Impression of Change is a simple questionnaire that reflects a clinician's 
belief about the efficacy of treatment (see Appendix 21). 
8.1.9 
Clinician Global Impression of Severity (CGIS) 
The Clinician Global Impression of Severity is a global index that is used by clinicians to rate  
the severity of a specific condition in patients (a single-state scale) (see Appendix 22). 
8.1.10 
Quality of life  
8.1.10.1 
Dermatology Life Quality Index (DLQI) 
The DLQI questionnaire will be used to assess treatment response on the 
life during the previous week (see Appendix 13)  
Subjects will be asked to recall their experiences during the previous week by responding to 10 
questions. The DLQI will be completed by the subject in the PRO prior to any safety or efficacy 
evaluations. The questionnaire is self-explanatory and handed to the subject, who is asked to fill 
it in without the need for a detailed explanation.   
8.1.10.2 
Nail Assessment in Psoriasis and Psoriatic Arthritis QoL (NAPPA-QoL) 
The NAPPA-QoL questionnaire will describe the QoL with nail psoriasis on the hands and/or 
feet over the past week (see Appendix 14). 
Only the fingernails will be evaluated in this study. 
8.1.10.3 
 Patient Global Impression of Change (PGIC) 
The Patient Global Impression of Change is a simple questionnaire that reflects a patient's belief 
about the efficacy of treatment (see Appendix 15).  


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8.1.10.4 
 Patient Global Impression of Change for pain (PGIC-P) 
Since the Patient Global Impression of Change is a versatile, global index that may be used to 
rate the change of any clinical condition, it will also be used in this protocol to evaluate change 
of nail pain (see Appendix 16), which will be called PGIC-P, and it will be recorded at the visits 
wherein PGIC will also be recorded. 
8.1.10.5 
 Patient Global Impression of Severity (PGIS) 
The Patient Global Impression of Severity is a global index that may be used to rate 
the severity of a specific condition (a single-state scale) (see Appendix 17).  
8.1.10.6 
 Patient Global Impression of Severity for pain (PGIS-P) 
Since the Patient Global Impression of Severity is a versatile global index that may be used to 
rate the severity of any clinical condition, it will also be used in this protocol to evaluate the 
intensity of nail pain (see Appendix 18), which will be called PGIS-P, and it will be recorded at 
the post-baseline visits wherein PGIS will also be recorded. 
8.2 
Safety Assessments   
Planned time points for all safety assessments are provided in the SoA (see Section 1.3).  
8.2.1 
Physical Examinations  
 
A complete physical examination will include assessments of general appearance; skin; 
head/neck; pulmonary, cardiovascular, gastrointestinal, external genitourinary, lymphatic, 
and musculoskeletal system; extremities; eyes (inspection and vision control); nose; throat; 
and neurologic status.  
 
A detailed examination of the skin should be performed at the time points indicated in the 
SoA (see Section 1.3) for the efficacy assessments (e.g., ViSENPsO, NAPSI, PGA-S, PASI, 
BSA, etc.).  
 
Height and weight will also be measured and recorded at Baseline before administration of 
the study treatment.  
 
Investigators should pay special attention to clinical signs related to previous serious illnesses.  
8.2.2 
Vital Signs  
 
Oral body temperature, pulse rate, blood pressure, and respiratory rate will be assessed at 
the time points specified in the SoA (see Section 1.3).  
 
Blood pressure and pulse measurements will be assessed in the supine position.  
 
Blood pressure and pulse measurements should be preceded by approximately 5 minutes of 
rest for the subject in a quiet setting without distractions (e.g., television, cell phones).  
 
Vital signs (to be taken before blood collection for laboratory tests) will consist of pulse and 
blood pressure measurement  using a validated device.  


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8.2.3 
Assessment of Suicidal Ideation and Behavior  
 
The subjects will be assessed for suicidal ideation and behavior at Screening using 
Screening Columbia-Suicide Severity Rating Scale (C-SSRS), at Baseline (using Baseline 
C-SSRS), and each subsequent visit using the C-SSRS Since Last Visit version 
(seeAppendix 18). 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 have a high risk of suicidality at the Screening assessment based on the 
12 months to Questions 4 or 5 in the suicidal ideation section or any positive response in the 
behavioral section of the C-SSRS should not be enrolled in the study.   
 
Those subjects who develop suicidal ideation during the study rated as high risk according 
to the above classification must be temporarily discontinued from receiving study treatment 
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 study treatment permanently. The presence of non-suicidal self-injurious 
behavior should be assessed on an individual basis.  
8.2.4 
Electrocardiograms  
 
A single 12-lead electrocardiogram (ECG) will be obtained as outlined in the SoA (see 
Section 1.3) using an ECG machine that automatically calculates the heart rate and 
measures PR, RR, QRS, QT, and QTc intervals.   
 
The ECG will be reviewed by an ECG vendor, and the instructions and guidelines for 
collection (e.g., equipment), transmission, and archiving of ECG data will be provided in 
the ECG Manual.  
8.2.5 
Tuberculosis Testing  
 
During the Screening Period, it must be determined and documented that a subject does not 
show evidence of active infection with TB.   
 
The subject must have a negative evaluation for TB within 4 weeks before initiating study 
treatment, defined as a negative QuantiFERON® test.  
 
Subjects with a positive or 2 successive indeterminate QuantiFERON® tests are allowed to 
enter the study if they have no history of active TB or symptoms of TB and a PA chest 
radiogram is performed (and with a report available at the study center) within 3 months of 
Screening with no evidence of TB (or of any other pulmonary infectious diseases).   
 
If there is evidence of prior LTBI, subjects must have a history of adequate prophylaxis per 
the local standard of care. If the presence of LTBI is established, treatment according to 


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local country guidelines must have been followed for at least 4 weeks prior to inclusion in 
the study.  
8.2.6 
Chest X-ray  
A chest X-ray will be performed at Screening if the subject has a positive or 2 indeterminate 
QuantiFERON results unless it has been taken and documented within the 3 months prior to 
Screening (the X-ray and associated report must be available at the study center). There must be 
no evidence of active TB or other pulmonary infectious diseases for the subject to be eligible for 
the study.  
8.2.7 
Clinical Safety Laboratory Assessments  
 
See Appendix 2 for the list of clinical laboratory tests to be performed and the SoA (see 
Section 1.3) for the timing and frequency of the tests.   
 
A central laboratory will perform all laboratory tests except urine pregnancy dipstick, which 
will be assessed by the center staff. However, local laboratory tests will be allowed in the 
event that the central laboratory results will not be available immediately, and the 
Investigator needs to make an immediate decision for any safety concerns based on the 
laboratory results.  
 
The Investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those that are not associated with the underlying disease unless 
 
 
All laboratory tests with values considered clinically significantly abnormal during 
values return to normal or Baseline or until stabilized or are no longer considered clinically 
significant by the Investigator or Medical Monitor.  
If such values do not return to normal/Baseline within a period of time judged reasonable by the 
Investigator, the etiology should be identified, if possible, and the Sponsor notified.  
All protocol-required laboratory assessments, as defined in Appendix 2, must be conducted in 
accordance with the Laboratory Manual and the SoA (see Section 1.3).   
8.3 
Adverse Events  
The safety and tolerability of subjects will be assessed by the incidence of treatment-emergent 
adverse events (TEAEs), laboratory test results, vital signs, ECGs, and physical examination 
findings.  
The definitions of an AE or SAE can be found in Appendix 3.  


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should contain an event term, date of onset, date of resolution, severity, action taken, outcome, 
relationship to study treatment, and a seriousness assessment.  
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information   
Any relevant observations made before the end of the Screening and Baseline visit (prior to the 
first dose of study treatment) are to be recorded on the AE eCRF, but will not be considered 
TEAEs and will be reported separately from TEAEs. Any relevant observations made after the 
Section 
1.3).  
In view of the long half-life of tildrakizumab at doses previously studied, subjects will continue 
to be monitored throughout the 20-week Observational Safety Follow-up period following the 
EoT (Week 52) visit. For the purposes of this study, any de
condition after the first dose of study treatment and up to the completion of the EoS visit should 
be considered an AE. For those subjects who may withdraw during the Observational Safety 
Follow-up period or wash-out period, at least 2 attempts should be made to collect the AEs.  
A hospitalization planned by the subject prior to signing the ICF is considered a therapeutic 
intervention and not the result of a new SAE and should be recorded as medical history. If the 
planned 
history is considered complete. However, if the event/condition worsens during the study, it must 
be reported as an AE.  
Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the AE section of the eCRF however will not be considered as 
TEAEs.  
All SAEs will be recorded and reported to the CRO within 24 hours, as indicated in Appendix 3. 
The Investigator will submit any updated SAE data to the CRO within 24 hours of it being 
available. The Investigator is responsible for informing the Ethics Committee of the SAE as per 
local requirements. All AEs/SAEs have to be reported to the Sponsor, whether or not considered 
causally related to the study treatment or to the study procedures.   
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including death, at any time after a 
subject has been discharged from the study, and he/she considers the event to be reasonably 
related to the study treatment or study participation, the Investigator must promptly notify the 
CRO.  
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3.  


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8.3.2 
Method of Detecting AEs and SAEs  
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non-
leading verbal questioning of the subject is the preferred method to inquire about AE 
occurrences.   
8.3.3 
Follow-up of AEs and SAEs  
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. Subjects who are discontinued from treatment because of SAEs, and 
non-serious AEs of special interest (AESI) (as defined in Section 8.3.6), will be followed until 
resolution, stabilization, the event is otherwise explained, or the subject is lost to follow-up (as 
defined in Section 7.3). Further information on follow-up procedures is given in Appendix 3.  
8.3.4 
Regulatory Reporting Requirements for SAEs  
All SAEs must be reported according to ICH GCP or local regulations, applying the regulation 
with the stricter requirements. The report will contain as much available information concerning 
which satisfies regulatory reporting requirements. The SAE report will be notified by 
Investigator within 24 hours of his/her awareness to t
personnel/CRO. These timelines apply to initial reports of SAEs and to all follow-up reports. All 
SAEs will be recorded on the SAE report form in the eCRF and source documents.   
The following minimum information must be included in the SAE form:  
 
Name, address and telephone number of the reporting Investigator,  
 
Study treatment details,  
 
Subject identification number, initials, gender, and date of birth,  
 
Description of the SAE, measures taken, and outcome.  
Relevant pages from the eCRF may be provided in parallel (e.g., medical history, concomitant 
drugs). Additional documents may be provided by the Investigator, if available (e.g., laboratory 
results, hospital report, autopsy report).   
The Investigator must respond to any request for follow-up information (e.g., additional 
information, outcome, final evaluation, other records where needed) or to any question, the 
necessary to ensure 
pharmacovigilance personnel to allow the Sponsor to meet strict regulatory timelines associated 
with expedited safety reporting obligations.  


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8.3.5 
Pregnancy  
Pregnancy itself is not regarded as an AE unless there is a suspicion that the study treatment may 
have interfered with the effectiveness of the contraceptive medication. If a pregnancy is reported 
for a subject, no further study treatment will be administered to this subject, and the outcome of 
all pregnancies (spontaneous miscarriage, elective termination, normal birth or congenital 
abnormality) must be followed up and documented. Follow-up should be performed up to 
delivery and examination of the newborn, after which a follow-up report should be sent with any 
new information regarding the pregnancy and the outcome of the birth.  
The pregnancy shall be followed every 3 months during pregnancy until its outcome and 1 
month post-delivery. If there are abnormalities present at delivery, the newborn will be followed 
for an appropriate period, or up to 3 months, to assess the functional and health status of the 
child.   
All congenital abnormalities/birth defects should be classified as SAEs. Spontaneous 
miscarriages should also be reported and handled as SAEs. Elective abortions without 
complications should not be handled as SAEs but should be reported as a follow-up report for the 
pregnancy. All outcomes of pregnancy must be reported to the Sponsor on a Pregnancy 
Outcomes Report Form.  
Pregnancy outcomes must be collected for the female partners of any males who took study 
treatment in this study. Consent to report information regarding these pregnancy outcomes 
should be obtained from the female partner.  
Pregnancies must be reported to IQVIA Clinical Pharmacovigilance and Safety Services using 
the reporting details provided in Appendix 3 within 24 hours of becoming aware of the 
pregnancy.   
8.3.6 
Adverse Events of Special Interest  
Injection site reactions, including injection site urticaria, pruritus, pain, reaction, erythema, 
inflammation, edema, swelling, bruising, hematoma, and hemorrhage, can be observed with the 
use of tildrakizumab. In general, these AE are well-tolerated and tend to disappear 
spontaneously, but if any of those occur in this study, they will be captured as AEs of special 
interest. 
The events of severe infections, malignancies (including non-melanoma and melanoma skin 
cancer), major adverse cardiovascular events (MACE)s, and study treatment-related 
hypersensitivity reactions (see Appendix 3) will be identified as AESIs for summarizing in this 
study. Major Adverse Cardiovascular Events include non-fatal stroke, non-fatal myocardial 
infarction, and cardiovascular death. An AESI must be reported to the sponsor as if it were an 
SAE.  


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8.3.7 
Events of Clinical Interest  
An Event of Clinical Interest (ECI) is a non-serious AE or occurrence that is designated to be of 
special interest and must be reported to the Sponsor as though it were an SAE.  
The following events are considered ECIs for this study:  
 An overdose of study treatment. An overdose that is not associated with clinical 
symptoms or abnormal laboratory results is to be reported as a non-serious ECI, using the 
termin
 
 An elevated 
phosphatase laboratory value that is < 2 × ULN, as determined by way of protocol-
specified laboratory testing or unscheduled laboratory testing.  
 Infections that require IV or IM antibiotics but do not meet the definition of an SAE will 
be designated a closely monitored AE for this study.  
 Depression, suicidal ideation, and other behavior events.  
8.4 
Treatment of Overdose  
A drug overdose is defined as the accidental or intentional use of a drug or medicine or an 
administration error in an amount that is higher than is normally used. Every overdose must be 
reported to IQVIA Clinical Pharmacovigilance and 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 
(see Section 6.1). 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.  
8.5 
Pharmacokinetics  
Pharmacokinetic parameters are not evaluated in this study.  
8.6 
Pharmacodynamics  
Pharmacodynamic parameters are not evaluated in this study.  
8.7 
Genetics  
Genetics are not evaluated in this study.  
8.8 
Biomarkers  
Biomarkers are not evaluated in this study.  


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8.9 
Health Economics or Medical Resource Utilization and Health Economics  
Health Economics/Medical Resource Utilization and Health Economics parameters are not 
evaluated in this study.  
 
 


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9.0 
STATISTICAL CONSIDERATIONS  
9.1 
Statistical Hypotheses  
The primary efficacy endpoint for this study is the proportion of subjects who achieve at least a 
75% improvement from baseline in total-mNAPSI at Week 28. The key secondary efficacy 
endpoint is the proportion of subjects with 
- 
 
and at least a 2-point decrease from baseline at Week 28 as measured by the ViSENPsO.For each 
endpoint, the tildrakizumab 100 mg dose will be compared with the placebo at Week 28.  
The overall study Type 1 error will be controlled for the primary and secondary efficacy 
endpoints using the step-down sequential procedure to control the overall type I error rate at 0.05 
level. The hierarchical order of testing the endpoints will follow the sequence provided below:  
9.2 
Sample Size Determination 
Conservatively assuming the mNAPSI75 response rates between active drugs and placebo of 35 
vs 10 (Results from a similar therapeutic agent, Adalimumab had shown response rates of 46 vs 
3 (43)) and assuming Normal Approximation and a Z-test (pooled) for proportions and a two-
3 subjects per treatment arm (for a total 86) will need to 
be randomized in a 1:1 ratio, stratified for prior use of TNF-alpha inhibitors (yes/no) and 
ns, 48 subjects in each arm, 
after accounting for up to 10% dropout, will yield at least 80(43)% power.  
At 80% power and alpha of 0.05, evaluable per arm subjects shall be 43. Considering 10% 
dropout study shall enroll 96 subjects [48 per arm] 
9.3 
Populations for Analyses  
For purposes of analysis, the analysis sets in Table 5 are defined.  


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Table 5: 
Analysis Sets     
Analysis Set  
Description  
Intent-to-Treat (ITT)  
All randomized subjects who were dispensed study treatment, 
regardless of whether treatment was taken by the subject or not. 
The primary efficacy population will be the ITT.   
Per Protocol Set (PPS)  
All subjects in the ITT population who complete the 28-week 
placebo-controlled treatment without any major protocol 
deviations. Details of exclusion criteria for the PPS will be 
specified in the Statistical Analysis Plan (SAP). The composition 
of the PPS will be determined in blind reviews of the database 
conducted prior to the analysis at Week 28.  
Safety Analysis Set (SAF) 
All randomized subjects who have taken at least 1 dose of study 
treatment.   
Subjects will be analyzed according to the treatment they actually 
received.  
Safety endpoints will be analyzed descriptively based on the SAP. 
 
9.4 
Statistical Analyses  
Statistical analyses will be performed using SAS® Version 9.4 or higher. All details regarding the 
statistical analysis and the preparation of tables, figures, and listings will be described in the 
SAP. The SAP will be developed and finalized before the unblinded interim analysis for analysis 
after all subjects complete Week 28 visit. This section is a summary of the planned statistical 
analyses of the primary and secondary endpoints.  
The following descriptive statistics will be used as applicable to summarize the study data unless 
otherwise specified:  
 
Continuous variables: sample size (n), mean, standard deviation (SD), median, minimum 
(min), and maximum (max).  
 
Categorical variables: frequencies and percentages.  
interest prior to the first intake of study treatment (this includes unscheduled visits). For 
numerical variables, change from Baseline will be calculated as the difference between the post-
baseline value and the corresponding Baseline value.   
Statistical comparisons for the primary and key secondary endpoints will be performed for 
inferential purpose following the testing approach described in Section 9.1; other statistical 
comparisons will be performed for descriptive purpose. COVID-19 related analyses will be 
specified in the SAP. 


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Individual subject data will be presented in listings.  
9.4.1 
Efficacy Analyses  
Table 6: 
Efficacy Analyses  
Endpoint  
Statistical Analysis Methods  
Primary and Key Secondary Efficacy Endpoints  
 
The proportion of subjects who achieve at 
least a 75% improvement from Baseline in 
total modified Nail Psoriasis Severity Index 
(mNAPSI) at Week 28. (Primary efficacy 
endpoint) 
 
- 
 
t 
least a 2-point decrease from baseline at Week 
28 as measured by the ViSENPsO. (Key 
secondary endpoint) 
 
The primary and key secondary analyses will be a 
comparison between the responders at Week 28 
across the tildrakizumab 100 mg and placebo 
treatment arms using a Cochran-Mantel-Haenszel 
test, incorporating prior use of TNF-alpha 
inhibitors (yes/no) 
kg or >90 kg) as stratification factors.   
In addition, M&N common risk (the response rate) 
difference between tildrakizumab 100 mg and 
placebo arm along with the 95% confidence 
interval will be estimated. These analyses will be 
based on the ITT population. All analyses will 
also be conducted for the PPS populations as 
supportive.  
For the primary endpoint, subjects with missing 
values will be imputed using non-responder 
imputation. The estimand framework for the 
primary and key secondary efficacy endpoints will 
be based on composite strategy approach and 
details will be described in the SAP. The 
following sensitivity analyses will be performed:  
 
PPS, using Observed Cases only. 
 
Other sensitivity analyses based on 
multiple imputation methods, in addition 
to a tipping point analysis, will be 
described in the SAP. 
 
Secondary and Exploratory Endpoints  
 
The proportion of subjects with, at least 3 
point decrease from Baseline in nail pain NRS 
score at Week 28 in subjects with baseline nail 
pain NRS score of > 3* 
 
The proportion of subjects achieving total-
fingernail mNAPSI 90, and mNAPSI 100 at 
Week 28.  
 
The proportion of subjects achieving total 
fingernail NAPSI 75, NAPSI 90 and NAPSI 
100 at Week 28 
 
Change in total-fingernail mNAPSI score 
from Baseline at Week 28.  
All secondary and exploratory efficacy endpoints 
will be analyzed using the ITT population. Binary 
endpoints up to Week 28 will be analyzed based 
on the methods described for the primary 
endpoint. For change-from-baseline at Week 28 
(continuous), secondary efficacy endpoints, 
MMRM model with treatment, visit (Weeks 4, 
8,12,16,20,24,28), prior use of TNF-alpha 
or >90 kg), treatment-by-visit interaction as 
factors and corresponding baseline value as a 
covariate will be performed. Secondary and 
Exploratory efficacy endpoints obtained from 


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Endpoint  
Statistical Analysis Methods  
 
Change in total-fingernail NAPSI score from 
Baseline at Week 28.  
 
Change in patient-reported nail pain NRS 
score  
 
Clinician-assessed proportions of ViSENPsO 
category results at Week 28 compared 
between treatment groups.  
 
The proportion of subjects achieving PASI 75, 
PASI 90, and PASI 100 at Week 28.  
 
The proportion of subjects achieving a PGA-S 
2-point reduction from Baseline at Week 28.  
 
Percentage change in total BSA involvement 
from Baseline at Week 28.  
 
Change from Baseline in mNAPSI, NAPSI, 
Nail Pain NRS, BSA, PGA-S, s-PGA, PASI 
and the proportions of ViSENPsO category 
results at  measured time points through Week 
52.  
 
Change from Baseline in DLQI score (total 
and domain scores),  NAPPA-QoL score, 
CGIC, CGIS, PGIC, PGIC-P, PGIS, and 
PGIS-P at measured time points through 
Week 52.  
 
The proportion of subjects with, at least, 30% 
decrease in Nail Pain NRS score from 
Baseline at Week 28 in subjects with a 
baseline nail pain NRS score of > 3
Week 28 to Week 52 will be evaluated using 
summary statistics.  
Abbreviations:  BSA = body surface area; CGIC = Clinician Global Impression of Change; CGIS = Clinician 
Global Impression of Severity; DLQI = Dermatology Life Quality Index; ITT = Intent to treat; LOCF = Last-
Observation-Carried-Forward; MMRM = Mixed Model Repeated Measures; mNAPSI = modified Nail Psoriasis 
Severity Index; NAPPA-QoL = Nail Assessment in Psoriasis and Psoriatic Arthritis Quality of Life; NAPSI = Nail 
Psoriasis Severity Index; NRS = Numeric Rating Scale; PASI = Psoriasis Area and Severity Index; PGA-S = 
Physician Global Assessment-Skin; PGIC = Patient Global impression of Change; PGIC-P = Patient Global 
impression of Change for pain; PGIS = Patient Global Impression of Severity; PGIS-P = Patient Global Impression 
of Severity for pain; PPS = Per Protocol Set; s-
 TNF = tumor necrosis 
factor; ViSENPsO = Visual Medical Scale to Evaluate Nail Psoriasis Severity 
 
9.4.2 
Safety Analyses  
All safety analyses will be performed on the Safety Analysis Set based on the actual treatment 
they received. All the safety will be summarized by the treatment arm, and by-subject listings 
will be provided.  


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9.4.2.1 
Adverse Events and Serious Adverse Events  
Treatment-emergent adverse events are defined as AEs that first occurred or worsened in 
severity after the first administration of study treatment.  
Adverse events will be coded using the most current version of the Medical Dictionary for 
Regulatory Activities (MedDRA). For each study treatment, the numbers of TEAEs and 
incidence rates will be tabulated by preferred term and system organ class.   
Treatment-emergent AEs by maximum severity, TEAEs by relationship to study treatment, 
SAEs, TEAEs leading to death, and TEAEs leading to discontinuation of study treatment will be 
tabulated for each treatment arm. Commonly occurring TEAEs, i.e., those that occur in 5% or 
more of the subjects in either treatment arm, will be summarized using descriptive statistics.  
The safety of tildrakizumab will be evaluated and reported as the percentage of subjects for the 
following TEAEs:  
 
Incidence, seriousness, and severity of all AEs, death cases, and discontinuations from 
the study.  
 
Percentage of subjects with severe infections, defined as any infection meeting the 
regulatory definition of an SAE or any infection requiring IV antibiotics whether or not 
reported as a serious event as per the regulatory definition.  
 
Percentage of subjects with malignancies (excluding carcinoma in situ of the cervix).  
 
Percentage of subjects with non-melanoma skin cancer.  
 
Percentage of subjects with melanoma skin cancer.  
 
Percentage of subjects with MACE (see Section 8.3.6).  
 
Percentage of subjects with study treatment-related hypersensitivity reactions (e.g., 
anaphylaxis, urticaria, angioedema, etc.).  
 
Percentage of subjects with injection site reactions (e.g., pain, erythema, edema, etc.).   
 
9.4.2.2 
Physical Examinations, 12-Lead ECG, Vital Signs, and Clinical Safety 
Laboratory Tests (Hematology, Biochemistry, and Urinalysis)  
Summaries and listings of data for physical examination findings, vital signs, hematology, 
biochemistry, and urinalysis laboratory tests will be presented. Appropriate descriptive statistics 
will be presented for the observed value at each scheduled assessment and for the corresponding 
change from Baseline.  
For hematology and biochemistry tests, listings of subject data will also flag any abnormal or 
out-of-range values. Clinically significant changes in the laboratory test parameters will be 
summarized and listed. Hematology and clinical laboratory data will be reported using 
Conventional Units.  


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Descriptive statistics will be used to present the safety outcomes, including physical examination 
results, weight, body mass index, 12-Lead ECG, vital signs measurements, and clinical 
laboratory test results.  
Change from Baseline will also be summarized for vital signs measurements and clinical 
laboratory test results.  
All ECG data results (normal/abnormal) will be summarized using frequency and percentages. 
Clinically significant abnormalities will be presented in by-subject listings.  
The incidence of treatment-emergent abnormal laboratory, vital signs, and ECG values will also 
be summarized using descriptive statistics.   
9.4.3 
Other Analyses   
No other analyses are planned for this study.  
9.4.4 
Missing Data  
Data from subjects who withdraw from the study, including AEs and any follow-up, will be 
included in the analyses as applicable.  
Handling of missing data is described in Table 6 of Section 9.4.1.  
9.5 
Interim Analyses (IA)  
An interim analysis may be performed. An external program-independent Data Monitoring 
Committee (DMC) may be established to conduct this unblinded interim analysis, review the 
unblinded results and make recommendations regarding the continuation of the study. To 
maintain the scientific reliability of possible final results and guard from introducing any 
potential bias into the conduct of the study and analysis, individuals involved in the interim 
analysis will not be involved in any operational aspect of the study. Further details of the 
unblinded interim analysis, in particular, its scope, the processes put in place to maintain study 
integrity, team structures, and responsibilities, will be documented in the Data Monitoring 
Committee Charter and/or a separate document. The interim analysis could include an unblinded 
sample size re-estimation (SSRE). The sample size of the study could be increased as a result of 
this SSRE. In the event of an increase in sample size, the total sample size of the study will not 
exceed a total of approximately 282 randomized subjects. 
a primary 
analysis may be conducted on available data to evaluate safety and efficacy and develop a 
clinical study report based on the data evaluated up to Week 28 visit. This analysis will be 
performed by the CRO; the Sponsor, and the DMC may not be involved in this analysis.     


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In the event of such an analysis, subjects who complete Part 1, all assessments of efficacy and 
safety before or on the date of injection at Week 28 (or Day 210 for subjects who do not have 
Week 28 injection), will be fully evaluated. Study centers, subjects, and study team members 
directly involved in study activities will remain blinded to study treatment assignments until the 
last subject completes their active treatment period (Week 52) and wash-out period. A separate 
document will provide further details related to the unblinding of personnel involved in reporting 
activities for the IAs. Sharing of subject-level unblinded information for the IAs will be confined 
to a designated unblinded study team.  
The SAP will describe the planned IAs in greater detail.  
9.6 
Monitoring Committee  
An independent Data Monitoring Committee may be established for periodic review of safety 
data from the study. The composition and responsibilities of the DMC will be described in the 
DMC Charter. The DMC will have access to unblinded data, including the interim analysis 
performed before the primary analysis.    
 


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10.0 
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Blauvelt A.,Papp K. A.,Griffiths C. E.,Randazzo B.,Wasfi Y.,Shen Y. K., et al. Efficacy 
and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with 
adalimumab for the continuous treatment of patients with moderate to severe psoriasis: 
Results from the phase III, double-blinded, placebo- and active comparator-controlled 
VOYAGE 1 trial. Journal of the American Academy of Dermatology. 2017;76(3):405-
17. 
38. 
Reich K.,Sullivan J.,Arenberger P.,Mrowietz U.,Jazayeri S.,Augustin M., et al. Effect of 
secukinumab on the clinical activity and disease burden of nail psoriasis: 32-week results 
from the randomized placebo-controlled TRANSFIGURE trial. The British journal of 
dermatology. 2018. 
39. 
Robinson A.,Kardos M.and Kimball A. B. Physician Global Assessment (PGA) and 
Psoriasis Area and Severity Index (PASI): why do both? A systematic analysis of 
randomized controlled trials of biologic agents for moderate to severe plaque psoriasis. 
Journal of the American Academy of Dermatology. 2012;66(3):369-75. 
40. 
Gottlieb A. B.,Merola J. F.,Chen R.,Levi E.and Duffin K. C. Assessing clinical response 
and defining minimal disease activity in plaque psoriasis with the Physician Global 
Assessment and body surface area (PGA x BSA) composite tool: An analysis of 
apremilast phase 3 ESTEEM data. Journal of the American Academy of Dermatology. 
2017;77(6):1178-80. 
41. 
Gottlieb A. B.,Chaudhari U.,Baker D. G.,Perate M.and Dooley L. T. The National 
Psoriasis Foundation Psoriasis Score (NPF-PS) system versus the Psoriasis Area Severity 
Index (PASI) and Physician's Global Assessment (PGA): a comparison. Journal of drugs 
in dermatology : JDD. 2003;2(3):260-6. 


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42. 
Elewski B. E.,Baker C. S.,Crowley J. J.,Poulin Y.,Okun M. M.,Calimlim B., et al. 
Adalimumab for nail psoriasis: efficacy and safety over 52 weeks from a phase-3, 
randomized, placebo-controlled trial. Journal of the European Academy of Dermatology 
and Venereology : JEADV. 2019;33(11):2168-78. 
43. 
Foley P.,Gordon K.,Griffiths C. E. M.,Wasfi Y.,Randazzo B.,Song M., et al. Efficacy of 
Guselkumab Compared With Adalimumab and Placebo for Psoriasis in Specific Body 
Regions: A Secondary Analysis of 2 Randomized Clinical Trials. JAMA dermatology. 
2018;154(6):676-83. 
44. 
Sampson H. A.,Munoz-Furlong A.,Campbell R. L.,Adkinson N. F., Jr.,Bock S. 
A.,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. The Journal of allergy and 
clinical immunology. 2006;117(2):391-7. 
45. 
Rich P.and Scher R. K. Nail Psoriasis Severity Index: a useful tool for evaluation of nail 
psoriasis. Journal of the American Academy of Dermatology. 2003;49(2):206-12. 
46. 
Cassell S. E.,Bieber J. D.,Rich P.,Tutuncu Z. N.,Lee S. J.,Kalunian K. C., et al. The 
modified Nail Psoriasis Severity Index: validation of an instrument to assess psoriatic nail 
involvement in patients with psoriatic arthritis. The Journal of rheumatology. 
2007;34(1):123-9. 
 
  
 


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11.0 
APPENDICES  
Appendix 1: 
Regulatory, Ethical and Study Oversight Considerations 
Regulatory and Ethical Considerations  
 
This study will be conducted in accordance with the protocol and with the following:  
o Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
International Ethical Guidelines.  
o Applicable International Council for Harmonisation Good Clinical Practice (ICH GCP) 
Guidelines.  
o Applicable laws and regulations.  
 
The protocol, protocol amendments, informed consent form (ICF), Investigator Brochure, and 
other relevant documents (e.g. advertisements) must be submitted to an IRB/IEC by the 
Investigator and reviewed and approved by the Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC) before the study is initiated.   
 
Any amendments to the protocol will require IRB/IEC and regulatory authority approval, 
when applicable, before implementation of changes made to the study design, except for 
changes necessary to eliminate an immediate hazard to subjects.   
 
The Investigator will be responsible for the following:  
o Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC. Notifying the IRB/IEC of SAEs or other significant safety findings as 
required by IRB/IEC procedures.  
o Providing oversight of the conduct of the study at the study center and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, 
European regulation 536/2014 for clinical studies (if applicable), and all other applicable 
local regulations.  
 
After reading the protocol, each Investigator will sign the protocol signature page and send a 
copy of the signed page to the Sponsor or representative (Appendix 23: ). The study will not 
start at any study center at which the Investigator has not signed the protocol.  
Financial Disclosure  
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study.  


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


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Quality Control and Quality Assurance  
According to the Guidelines of GCP (CPMP/ICH/135/95), IQVIA is responsible for 
implementing and maintaining quality assurance and quality control systems with written 
standard operating procedures (SOPs). Quality control will be applied to each stage of data 
handling.  
The following steps will be taken to ensure the accuracy, consistency, completeness, and 
reliability of the data:  
 
Central laboratories for clinical laboratory parameters.  
 
Study center Initiation visit.  
 
Early study center visits post-enrollment.  
 
Routine study center monitoring.  
 
Ongoing study center communication and training.  
 
Data management quality control checks.  
 
Continuous data acquisition and cleaning.  
 
Internal review of data.  
 
Quality control check of the final clinical study report (CSR).  
In addition, Sponsor and/or IQVIA Quality Assurance Department may conduct periodic audits 
of the study processes, including, but not limited to study center, central laboratories, vendors, 
clinical database, and final CSR. When audits are conducted, access must be authorized for all 
study-related documents, including medical history and concomitant medication documentation 
ulatory authorities.  
Monitoring  
Sponsor has engaged the services of a Contract Research Organization (CRO), IQVIA, to 
perform all monitoring functions within this clinical study. IQVIA
accordance with IQVIA
establish and maintain regular contact between 
the Investigator and Sponsor.  
The monitor will evaluate the competence of the study center, informing Sponsor about any 
problems relating to facilities, technical equipment, or medical staff. During the study, the 
monitor will check that written informed consent has been obtained from all subjects correctly 
and that data are recorded correctly and completely. The monitor is also entitled to compare 
entries in the electronic case report forms (eCRFs) with corresponding source data and to inform 
the Investigator of any errors or omissions. The monitor will also assess and control adherence to 
the protocol and ICH/GCP guidelines at the study center. The monitor will arrange for the supply 
of study treatment, ensure proper study treatment dispensing/accountability, and appropriate 
storage conditions are maintained.  


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Monitoring visits will be conducted according to all applicable regulatory requirements and 
standards. Regular monitoring visits will be made to each center while subjects are enrolled in 
the study.   
During monitoring visits, all entries in the eCRFs will be compared with the original source 
documents (source data verification). For the following and all other items, this check will be 
100%:  
 
Subject identification number.  
 
Subject consent obtained.  
 
Subject eligibility criteria (inclusion and exclusion criteria).  
 
IMP administration. 
 
Efficacy variables (not directly entered into electronic patient-reported outcome [ePRO]).  
 
Safety variables.  
 
Medical record of adverse event (AE).  
Quality Management  
A system should be implemented to manage quality throughout all stages of the study process 
with the focus on study activities essential to ensuring human subject protection and the 
reliability of study results. The methods used to assure and control the quality of the trial should 
be proportionate to the risks inherent in the trial and the importance of the information collected. 
All aspects of the study should be operationally feasible and should avoid unnecessary 
complexity, procedures, and data collection.   
During protocol development, processes, and data that are critical to ensure human subject 
protection and the reliability of trial results should be identified. Risks should be considered at 
both the system level (e.g., SOPs, computerized systems, and personnel) and clinical trial level 
(e.g., trial design, data collection, informed consent process). The approach used to reduce risk to 
an acceptable level should be proportionate to the significance of the risk. Predefined quality 
tolerance limits should be established, taking into consideration the medical and statistical 
characteristics of the variables as well as the statistical design of the trial, to identify systematic 
issues that can impact subject safety or reliability of trial results. Detection of deviations from the 
predefined quality tolerance limits should trigger an evaluation to determine if action is needed.  
Quality management activities should be documented and communicated to those who are 
involved in or affected by such activities, to facilitate risk review and continual improvement 
during clinical trial execution.  
Data Management/Coding  
Data generated within this clinical study will be handled according to the relevant SOPs of the 
Data Management and Biostatistics departments of IQVIA.  


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


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


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completion. A study center is considered closed when all required documents and study supplies 
have been collected, and a study center closure visit has been performed.  
The Investigator may initiate study center closure at any time, provided there is reasonable cause, 
and sufficient notice is given in advance of the intended termination.  
Reasons for the early closure of a study center by the Sponsor or Investigator may include but 
are not limited to:  
 
Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC or 
 
 
Inadequate recruitment of subjects by the Investigator.  
 
Discontinuation of further study treatment development.  
Publication Policy  
The data generated by this study are confidential information of the Sponsor. 
 
 
 
 
 


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Appendix 2: 
Clinical Laboratory Tests 
 
The tests detailed in Table 7 will be performed by the ACM Global Laboratories. The time 
points are specified in the Schedule of Activities (SoA) (see Section 1.3).   
 
Local laboratory tests will be allowed in the event that the central laboratory results will not 
be available immediately and the Investigator needs to take an immediate decision for any 
safety concerns. If a local sample is required, it is important that the sample for central 
analysis is obtained at the same time.   
 
Local laboratory results must be entered into the eCRF.   
 
Urine pregnancy test will be performed at the study center prior to study treatment 
administration.  
 
Protocol-specific requirements for inclusion or exclusion of subjects are detailed in Section 
5.0 of the protocol.  
 
Additional tests may be performed at any time during the study as determined necessary by 
the Investigator or required by local regulations.  
 
Investigators must document their review of each laboratory safety report.  
Table 7: 
Protocol-required Safety Laboratory Assessments  
Laboratory 
Assessments  
Parameters  
Hematology  
Hemoglobin  
White Blood Cell Count (WBC)* 
Hematocrit  
* WBC with Differential only if WBC is 
abnormal  
Platelet count  
Clinical Chemistry  
Alanine aminotransferase (ALT)  
Creatinine  
Albumin 
Gamma glutamyl transferase (GGT) 
Alkaline phosphatase (ALP)  
Glucose  
Aspartate aminotransferase (AST) 
Potassium 
Bicarbonate  
Phosphate (Inorganic)  
Bilirubin (Total) 
Protein (Total) 
Bilirubin (Direct-only if the total is 
elevated) 
Sodium  
Calcium  
Blood urea nitrogen (urea)  
Chloride 
Creatine Kinase 
Uric acid 
Triglycerides 
Lactate dehydrogenase 
Lipids (fasting)
Total Cholesterol (fractions)
Triglycerides
Serum pregnancy a  
Human chorionic gonadotropin (hCG) pregnancy test (as needed for women of 
childbearing potential) 
Follicle-stimulating 
hormone (FSH)  
As needed in a postmenopausal woman aged over 45 years with at least 1 year of 
amenorrhea without an alternative medical cause.  


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Laboratory 
Assessments  
Parameters  
Urinalysis  
Bilirubin   
pH  
Blood  
Protein  
Glucose  
Specific gravity  
Ketones  
Urobilinogen  
Leukocyte esterase (if it is abnormal, 
a full microscopic examination may 
be performed) 
Microbiology (At the discretion of 
Investigator based on urinalysis results)  
Nitrites  
Microscopy (At the discretion of 
Investigator based on urinalysis results)  
Viral serologya  
Hepatitis B surface antigen   
  
Hepatitis C Antibody  
  
HIV antibodies  
  
Tuberculosis (TB) 
Screeninga  
QuantiFERON® test  
NOTES:  
a Only during Screening  
- The results of each test must be entered into the electronic case report form (eCRF). The date and exact 
time of sample collection must be recorded.  
- Blood samples are to be collected (prior to study treatment administration), after an electrocardiogram 
(ECG) and vital sign measurements. At visits where lipids are to be assessed, the blood samples are to 
be collected (prior to study treatment administration) after 12 hours fasting, following ECG and vital 
sign measurements.  
 
 


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Appendix 3: 
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
Definition of AE  
An AE is any untoward medical occurrence in a patient or subject, temporally associated with 
the use of study treatment, whether or not considered related to the study treatment.  
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use 
of study treatment.  
Events Meeting the AE Definition   
 Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from Baseline, considered clinically significant in the 
medical and scientific judgment of the Investigator (ie, not related to progression of 
underlying disease).  
 Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or severity of the condition.  
 New conditions detected or diagnosed after study treatment administration even though it 
may have been present before the start of the study.  
 Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.  
 Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae.  
 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy 
will be reported as AE or SAE if they fulfill the definition of an AE or SAE. 
Events NOT Meeting the AE Definition   
 Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
 
 The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder bein
condition.  
 Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads 
to the procedure is the AE.  


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 Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).  
 Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.  
 Pregnancy itself is not regarded as an AE unless there is suspicion that the study 
treatment may have interfered with the effectiveness of a contraceptive medication. If a 
pregnancy is reported for a subject, no further study treatment will be administered to this 
subject and the outcome of all pregnancies (spontaneous miscarriage, elective 
termination, normal birth or congenital abnormality) must be followed up and 
documented. Follow-up should be performed up to delivery and examination of the 
newborn, after which a follow-up report should be sent with any new information 
regarding the pregnancy and the outcome of the birth.  
 All congenital abnormalities/birth defects should be classified as SAEs. Spontaneous 
miscarriages should also be reported and handled as SAEs. Elective abortions without 
complications should not be handled as SAEs but should be reported as a follow-up 
report for the pregnancy. All outcomes of pregnancy must be reported to the Sponsor on a 
Pregnancy Outcomes Report Form.  
 Pregnancy outcomes must be collected for the female partners of any males who took 
study treatment in this study. Consent to report information regarding these pregnancy 
outcomes should be obtained from the female partner.  
 The pregnancy shall be followed every 3 months during pregnancy till until its outcome 
and 1 month post-delivery. If there are abnormalities present at delivery, the newborn 
will be followed for an appropriate period, or up to 3 months, to assess the functional and 
health status of the child  
 Pregnancies must be reported to IQVIA Clinical Pharmacovigilance and Safety Services 
using the reporting details provided in Section 8.3.5 within 24 hours of awareness. 
Definition of SAE  
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g. hospitalization for signs/symptoms of the disease under study, death due to the 
progression of disease). 
An SAE is defined as, but is not limited to, an event that:  
a) Results in death  
Death is not an AE in itself, but an outcome. The cause of death is the AE, which resulted in 
death. 
b) Is life-threatening  
Life-threatening means that the subject was at immediate risk of death at the time of the SAE; it 
does not refer to an SAE that hypothetically might have caused death if it had been more severe.  


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c) Requires 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) for pre-existing condition, or a 
procedure required by the Clinical  
Investigation Plan, without a serious deterioration in health or if the hospitalization is clearly not 
associated with an AE (e.g. social hospitalization) will not be considered an SAE, unless any of 
the above criteria are fulfilled over the course of the hospitalization due to unplanned 
hospitalization whereby it is administratively impossible to release the subject home is not 
necessarily an SAE. Complications that occur during hospitalizations are AEs unless they would 
qualify as an SAE for any of the above criteria. If the complication delays subject release from 
hospital, then the AE becomes an SAE. Hospitalizations which are not performed due to an AE 
are not regarded as SAEs.  
d) Results in persistent or significant disability/incapacity  
The term significant disability refers to any condition that impairs physical/physiological well-
being to the extent that the subject is unable to function normally. Physical disability may include, 
but is not limited to, permanent disability of locomotion or motility, but also systemic permanent 
dysfunction including heart failure, liver insufficiency or pulmonary fibrosis. 
e) Is a congenital anomaly/birth defect 
f) Is an important medical event:  
Important medical events that may not result in death, be life-threatening or require 
hospitalization may be considered as an SAE when, based on appropriate medical judgment, they 
may jeopardize the subject, or the subject may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 
Recording and Follow-up of AE and/or SAE Definition of the Adverse Event Reporting 
Period  
The AE/SAE reporting period for safety surveillance begins after subject signs ICF. The safety 
surveillance continues until 20 weeks from last dos 
e of study treatment administration. Any AE/SAE occurred post 20 weeks from last dose of 
study treatment administration will be reported if it is considered related to study treatment by 
the Investigator.  
 
 


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Unexpected Adverse Event  
Any adverse event that is not identified in nature, severity, frequency, or outcome in Investigator 
Brochure (IB) will be considered as unexpected. Most recent version of IB will serve as 
reference safety information for assessment of expectedness of SAEs. 
AE and SAE Recording 
 When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (e.g. hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event.  
 The Investigator will then record all relevant AE/SAE information in the eCRF. Each 
event must be recorded separately.  
 
records to IQVIA Clinical Pharmacovigilance and Safety Services in lieu of completion 
of the AE/SAE eCRF page.  
 There may be instances when copies of medical records for certain cases are requested by 
IQVIA Clinical Pharmacovigilance and Safety Services. In this case, all subject 
identifiers, with the exception of the subject number, will be redacted on the copies of the 
medical records before submission to IQVIA Clinical Pharmacovigilance and Safety 
Services.  
 The Investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.  
Assessment of Severity 
The Investigator will make an assessment of severity for each AE and SAE reported during the 
study and assign it to 1 of the following categories: 
 Mild: An event that is easily tolerated by the subject, causing minimal discomfort and not 
interfering with everyday activities.  
 Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities.  
 Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with a SAE. Severe is a category utilized for rating the 
severity of an event; and both AEs and SAEs can be assessed as severe.  
described in the definition of an SAE, NOT when it is rated as severe. 
 
 


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Assessment of Causality: 
The Investigator is obligated to assess the relationship between study treatment and each 
occurrence of each AE/SAE. The AE must be characterized as certainly/definitely related,  
unrelated, unlikely to be related, possibly related, or probably related. 
o 
abnormality, occurring in a plausible time relationship to drug administration, and 
which cannot be explained by concurrent disease or other drugs or chemicals. The 
response to withdrawal of the drug (de-challenge) should be clinically plausible. The 
event must be definitive pharmacologically or phenomenologically, using a satisfactory 
re-challenge procedure if necessary.  
o 
s to suggest 
a causal relationship, rather than a relationship cannot be ruled out. 
o 
unknown; however, the AE is not reasonably supported by other conditions.  
o 
study treatment and the AE. Other conditions, including chronic illness, progression or 
expression of the disease state or reaction to concomitant therapy, appear to explain the 
reported AE.  
o 
caused the AE. 
 The Investigator will use clinical judgment to determine the relationship.  
 Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study treatment administration, 
will be considered and investigated.  
 
Information, for marketed products, in his/her assessment.  
 For each AE/SAE, the Investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.  
 There may be situations in which an SAE has occurred, and the Investigator has minimal 
information to include in the initial report to IQVIA Clinical Pharmacovigilance and Safety 
Services. However, it is very important that the Investigator always make an assessment of 
causality for every event before the initial transmission of the SAE data to IQVIA Clinical 
Pharmacovigilance and Safety Services.  
 The Investigator may change his/her opinion of causality in light of follow-up information 
and send a  
 SAE follow-up report with the updated causality assessment.  
 The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 


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


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Safety Reporting to Sponsor 
IQVIA Clinical Pharmacovigilance and Safety Services will forward the SAE and Pregnancy 
afety representatives within 1 business day or 3 calendar days 
(whichever is earlier) of becoming aware of it. 
 
 


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Appendix 4: 
Anaphylaxis 
The clinical criteria for diagnosing anaphylaxis are as follows:  
 Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled:  
 
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, swollen lips-tongue-uvula)  
 
AND AT LEAST ONE OF THE FOLLOWING:  
o Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced 
PEF, hypoxemia)  
o Reduced BP or associated symptoms of end-organ dysfunction (e.g. hypotonia 
[collapse], syncope, incontinence)  
 
Two or more of the following that occur rapidly after exposure to a likely allergen for that 
patient (minutes to several hours):  
o Involvement of the skin-mucosal tissue (e.g., generalized hives, pruritus or 
flushing, swollen lips-tongue-uvula)  
o Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced 
PEF, hypoxemia) 
o Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, 
incontinence)  
Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)  
 
Reduced BP after exposure to known allergen for that patient (minutes to several hours):
o Infants and children: low systolic BP (age specific) or greater than 30% decrease 
in systolic BP  
o Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that 
 
Abbreviations: BP = blood pressure; PEF = peak expiratory flow  
Data source: (44) 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;117:391-397.  
 
 
 
 
 
  
 


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Appendix 5: 
Contraceptive Guidance and Collection of Pregnancy 
Information  
Definitions:  
Woman of Childbearing Potential (WOCBP)  
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).  
Women in the following categories are not considered WOCBP  
1. Premenarchal  
2. Premenopausal female with 1 of the following:  
a) Documented hysterectomy.  
b) Documented bilateral salpingectomy.  
c) Documented bilateral oophorectomy.  
Note: Documentation can c
medical records, medical examination, or medical history interview.  
3. Postmenopausal female:  
a) A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 12 
months of amenorrhea, a single FSH measurement is insufficient.   
b) Females on HRT and whose menopausal status is in doubt will be required to use 1 of the 
non-estrogen hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation 
of postmenopausal status before study enrollment.  
Contraception Guidance  
Male subjects  
 
Male subjects with female partners of childbearing potential are eligible to participate if they 
agree to ONE of the following during the study and for 6 months after the last dose of study 
treatment:   
o Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent.  
o Agree to use a male condom plus partner use of a contraceptive method with a failure 
rate of <1% per year when having penile-vaginal intercourse with a woman of 
childbearing potential who is not currently pregnant.  


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In addition, male subjects must refrain from donating sperm for the duration of the study and 
for 6 months after the last dose of study treatment.  
 
Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile penetration 
for the duration of the study and for 6 months after the last dose of the study treatment.  
Female subjects     
Female subjects of childbearing potential are eligible to participate if they agree to use a highly 
effective method of contraception consistently and correctly, as described in the table below.  
Highly Effective Contraceptive Methods  
Highly Effective Contraceptive Methods That Are User Dependent a  Failure rate of <1% per year when 
used consistently and correctly.   
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation  
Oral.   
Intravaginal.  
 Transdermal. 
Progestogen -only hormonal contraception associated with inhibition of ovulation 
Oral.  
Injectable.   
Highly Effective Methods That Are User Independent a  
Implantable progestogen -only hormonal contraception associated with inhibition of ovulation 
Intrauterine device.  
Intrauterine hormone-releasing system (IUS).  
Bilateral tubal occlusion. 
Vasectomized partner  
A vasectomized partner is a highly effective birth control method provided that the partner is the sole male sexual 
partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional, highly effective 
method of contraception should be used.  
Sexual abstinence  
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study treatment. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of 
the subject.  
NOTES:  
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies.  
  
Pregnancy Testing:  
 
WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive serum pregnancy test at Screening and urine pregnancy test on Day 1 (prior to study 
treatment administration).  
 
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Pregnancy testing will be performed whenever a menstrual cycle is missed or when pregnancy 
is otherwise suspected. Positive urine pregnancy test result should be confirmed with serum 
test.  
Collection of Pregnancy Information  
Male subjects with partners who become pregnant   
 
The Investigator w
partner who becomes pregnant while the male subject is in this study. This applies only to 
male subjects who receive study treatment.  
 
After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
partner will also be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and child will be forwarded to the Sponsor. Generally, the follow-up will 
be every 3 months during pregnancy until its outcome and 1 month post-delivery. Any 
termination of the pregnancy will be reported regardless of fetal status (presence or absence 
of anomalies) or indication for the procedure.   
Female Subjects who become pregnant   
 
The Investigator will collect pregnancy information on any female subject who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
subject will be followed to determine the outcome of the pregnancy. The Investigator will 
collect follow-up information on the subject and the neonate and the information will be 
forwarded to the Sponsor. Generally, follow-up will be every 3 months during pregnancy until 
its outcome and 1 month post-delivery. Any termination of pregnancy will be reported, 
regardless of fetal status (presence or absence of anomalies) or indication for the procedure. 
The method of reporting pregnancy will be similar to SAE reporting as mentioned in 
Appendix 3.  
 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous abortion 
is always considered to be an SAE and will be reported as such.  
 
Any post-study pregnancy related SAE considered reasonably related to the study treatment 
by the Investigator will be reported to the Sponsor as described in Section 8.3.4. While the 
Investigator is not obligated to actively seek this information in former subjects, he or she 
may learn of an SAE through spontaneous reporting.   
 
Any female subject who becomes pregnant while participating in the study will discontinue 
study treatment or be withdrawn from the study.  


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The pregnancy shall be followed every 3 months during pregnancy till its outcome and 1 
month post-delivery. If there are abnormalities present at delivery, the newborn will be 
followed for an appropriate period, or up to 3 months, to assess the functional and health 
status of the child.   
 


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Appendix 6: 
Definition and Diagnosis of Fungal Nail Infection 
Definition  
Fungal nail infections (Onychomycosis) are common infections of the fingernails or toenails 
that can cause the nail to become discolored, thick, and more likely to crack and break.  
 Physical findings in fungal nail infection:             
o Thickening      
o Discoloration  
o Friability         
o Deformed  
o Hypertrophic or hyperkeratotic  
o Subungual debris  
If any of the above physical findings are seen, nail scrapings should be sent for direct 
microscopy or fungal culture  
 Laboratory findings:   
o Direct microscopy: Identification of 
hyphae, pseudohyphae, or spores  
o Fungal culture: Negative or positive  
 
 


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Appendix 7:  
Nail Psoriasis Severity Index (NAPSI) 
The nail is divided with imaginary horizontal and longitudinal lines into quadrants. Each nail is 
given a score for nail bed psoriasis (0-4) and nail matrix psoriasis (0-4) depending on the 
presence of any of the features of nail psoriasis in that quadrant. 
1. Evaluation 1: Nail matrix. In each quadrant of the nail, nail matrix psoriasis is evaluated by 
presence of any of the nail matrix features (pitting, leukonychia red spots in the lunula, 
crumbling):  
0 for none, 1 if present in 1 quadrant of the nail, 2 if present in 2 quadrants of the nail, 3 if 
present in 3 quadrants of the nail, and 4 if present in 4 quadrants of the nail. 
2. Evaluation 2: Nail bed. Nail bed psoriasis is evaluated by the presence of any of the nail bed 
dyschroma): 0 for none, 1 for 1 quadrant only, 2 for 2 quadrants, 3 for 3 quadrants, and 4 for 4 
quadrants. 
3. Each nail gets a matrix score and a nail bed score, the total of which is the score for that nail 
(0-8). 
4. Each nail is evaluated, and the sum of all the nails is the total NAPSI score. The sum of the 
scores from all fingernails is 0-80. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference: Rich P and Scher RK. J Am Acad Dermatol 2003 Aug; 49(2):206-12 (45) 


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Appendix 8: 
modified Nail Psoriasis Severity Index (mNAPSI) 
question which grade to give, your answer should be the lower of the grades. Three features or 
groups of features (pitting, onycholysis and oil-drop dyschromia, and crumbling) of each 
fingernail will be graded on a scale from zero to 3, according to the directions below. Four 
features (leukonychia, splinter hemorrhages, hyperkeratosis, and red spots in the lunula) will be 
graded as either present or absent for each fingernail.  
Nail Features  
Score and Description  
Onycholysis 
and 
oil-drop 
(salmon patch) dyschromia  
0: No onycholysis or oil drop dyschromia present  
1: 1 10% of the nail has onycholysis or oil-drop dyschromia 
2: 11 30% of the nail has onycholysis or oil-drop dyschromia 
3: > 30% of the nail has onycholysis or oil-drop dyschromia  
Pitting  
0: No pitting  
1: 1 10 pits  
2: 11 49 pits  
3: > 50 pits  
Nail plate crumbling  
0: No crumbling  
1: 1 25% of the nail has crumbling  
2: 26 50% of the nail has crumbling  
3: > 50% of the nail has crumbling  
Leukonychia  
0: Absent  
1: Present  
Splinter hemorrhages  
0: Absent  
1: Present  
Hyperkeratosis  
0: Absent  
1: Present  
Red spots in the lunula  
0: Absent  
1: Present  
TOTAL SCORE RANGE   
0-130 (maximum of 13 for each fingernail)  
Reference: Cassell SE, Bieber JD, Rich P et al. J Rheumatol 2007; 34: 123-129  (46)  
 
 


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Appendix 9: 
 (PGA-S) 
point. Overall lesions will be graded for thickness, erythema, and scaling based on the scales 
below. The sum of the 3 scales will be divided by 3 to obtain the final PGA score. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix 10:
Psoriasis Area and Severity Index (PASI)


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Appendix 11: 
Numeric Rating Scale (NRS) 
. 
 
Reference: 
https://www.painscale.com/article/numeric-rating-scale-nrs. 
 
 
 
 
 


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Appendix 13:
Dermatology Life Quality Index (DLQI)


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Appendix 14: 
Nail Assessment in Psoriasis and Psoriatic Arthritis QoL (NAPPA-
QoL) 
 
  
 
 


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Appendix 15: 
Patient Global Impression of Change (PGIC) 
Please choose the response below that best describes the overall change in your nail psoriasis 
since you started taking the study medication.  
 
 
 
se  
 
 
Reference:  
 
https://www.fda.gov/media/116281/download.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix 16: 
Patient Global Impression of Change for pain (PGIC-P) 
Please choose the response below that best describes the overall change in your nail pain since 
you started taking the study medication.  
 
 
 
 
 
 
Reference:  
 
https://www.fda.gov/media/116281/download.  
 
 
 
 
 
 


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Appendix 17:  
Patient Global Impression of Severity (PGIS) 
Please choose the response below that best describes the severity of your nail psoriasis over the 
past week. 
 
 
 
 
 
 
References:  
https://www.fda.gov/media/116281/download. 
Coon CD, Cappelleri JC.  Interpreting change in scores on patient-reported outcome 
instruments.  Therapeutic Innovation & Regulatory Science  2016; 50(1):22-29. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix 18: 
Patient Global Impression of Severity for pain (PGIS-P) 
Please choose the response below that best describes the severity of your nail pain over the past 
week. 
 
 
 
 
 
 
References: 
https://www.fda.gov/media/116281/download. 
Coon CD, Cappelleri JC.  Interpreting change in scores on patient-reported outcome 
instruments.  Therapeutic Innovation & Regulatory Science  2016; 50(1):22-29. 
 
 
 


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Appendix 19: 
Columbia-Suicide Severity Rating Scale   
1) C-SSRS Screening  
 
  


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C-SSRS Baseline  
  
 


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2) C-SSRS Since Last Visit  
 
  


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Appendix 20: 
-PGA): 
 
 
 
Reference: Chow C, Simpson MJ, Luger TA, Chubb H, Ellis CN. Comparison of three methods 
for measuring psoriasis severity in clinical studies (Part 1 of 2): change during therapy in 
Psoriasis Area and Severity Index, Static Physician's Global Assessment and Lattice System 
Physician's Global Assessment. J Eur Acad Dermatol Venereol. 2015 Jul;29(7):1406-14.  


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Appendix 21: 
Clinician Global Impression of Change (CGIC) 
Please choose the response below that 
 
psoriasis since he/she started taking the study medication.  
 
 
 
 
 
 
 


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Appendix 22: 
Clinician Global Impression of Severity (CGIS) 
 psoriasis 
today. 
 
 
 
 
 
 


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Appendix 23: 
Signature of Investigator 
PROTOCOL TITLE:  A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical 
Study to Assess the Efficacy and Safety of Tildrakizumab in the Treatment of Moderate to Severe 
Nail Psoriasis.  
PROTOCOL NO:  
TILD-18-19  
 
VERSION:   
Amendment 3, 23 Dec 2022 
This protocol is a confidential communication of Sun Pharmaceutical Industries Limited. I 
confirm that I have read this protocol, I understand it, and I will work according to this protocol. 
I will also work consistently with the ethical principles that have their origin in the Declaration 
of Helsinki and that are consistent with Good Clinical Practices and the applicable laws and 
regulations. Acceptance of this document constitutes my agreement that no unpublished 
information contained herein will be published or disclosed without prior written approval from 
the Sponsor.  
I have read this protocol in its entirety and agree to conduct the study accordingly:  
  
Signature of Investigator:     __________________________            Date:  ________  
Printed Name:                       ___________________________  
Investigator Title:                 ___________________________  
  
Name/Address of Center:      _________________________  
  
  
  
         __________________________  
  
  
  
        ___________________________  
 
 

SAP_001.pdf: 
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Assess 
the Efficacy and Safety of Tildrakizumab in the Treatment of Moderate to Severe Nail Psoriasis. 
Document: Statistical Analysis Plan 
NCT number: NCT03897075 
Document date: 08 Aug 2024