An Open-Label, Real World Study Evaluating the Long-Term Quality of Life of Tildrakizumab in Adult Patients With Moderate to Severe Plaque Psoriasis
Phase: PHASE4
Conditions: Psoriasis
Sponsor: Sun Pharmaceutical Industries Limited

 
 
Official Title:  An Open-Label, Real World Study Evaluating the Long-Term Quality of Life   
of Tildrakizumab in Adult Patients With Moderate to Severe Plaque Psoriasis 
Document:   Clinical Study Protocol 
NCT number: NCT03718299 
Date: 2 January 2020 

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Pharmaceuticals Industries, Inc except to the extent necessary to obtain informed 
consent from those persons to whom the drug may be administered. 
 
 
 

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 Study Procedures 
The following procedures will take place according to the visit schedule.   
 Study procedures will be explained by the study coordinator 
and the subject will provide signed, written informed consent. Consent must be 
signed prior to the initiation of any study-related procedures. Subjects will be 
asked whether they are willing to be contacted by a representative of the Sponsor 
to share their experience.  Inclusion/Exclusion (I/E) criteria will be reviewed to 
determine subject eligibility.  Demographic information, medical history including 
review of concomitant medications and psoriasis treatment history, full physical 
exam including psoriasis assessments, clinical laboratories including CBC, 
chemistry panel, virology/HIV screen, serum pregnancy test (if applicable), and 
chest x-ray (if applicable) will be obtained or performed at this visit. 
 
 Review of (I/E) criteria and concomitant medications.  Female 
subjects of child-bearing potential must have a negative urine pregnancy test 
(UPT  to continue in the study. Limited physical exam including psoriasis 
assessments (including PASI), full-body photography, quality of life measures, 
patient reported questionnaires, and study drug injection will be completed.  
 
 Review of interim medical history, 
AEs and concomitant medications.  Limited physical exam including psoriasis 
assessments (PASI at Weeks 4, 16, 28 and 52), UPT (Weeks 4, 16, 28, 40 and 
52, if applicable), quality of life measures, and patient questionnaires will be 
completed. Full-body photography will be performed at Weeks 16, 28, 52. WPAI 
                                            
 

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will be performed at Weeks 16, 28, 40, 52.  Study drug injections will occur at 
Weeks 4, 16, 28, 40 and 52. 
 
 Review of interim medical history, AEs and concomitant 
medications.  Limited physical exam including psoriasis assessments, UPT (if 
applicable), quality of life measures, patient questionnaires  and end of study 
procedures will be completed.  
Study Measurements 
The following assessments will be performed. 
 
1. Quality of life will be measured using the following validated instruments:  
a. Psychological General Well-Being scale (PGWB) 
b. Dermatology Life Quality Index (DLQI) 
 
2. Physical parameters, patient satisfaction/happiness with treatment/psoriasis 
control, and impact on work productivity will also be measured using the 
following instruments:  
a. Body Surface Area (BSA) 
b. Static Physician’s Global Assessment (sPGA) 
c. Psoriasis Area Severity Index (PASI) 
d. Itch Numerical Rating Scale  
e. Pain Numerical Rating Scale  
f. 
Scaling Numerical Rating Scale 
g. Tildrakizumab Overall Satisfaction Numerical Rating Scale 
h. Patient Happiness with Psoriasis Control Numerical Rating Scale 
i. 
Treatment Satisfaction Questionnaire for Medication (TSQM) 
j. 
Work Productivity and Activity Impairment scale (WPAI-PSO) 
 
3. All AEs will be recorded to assess safety.  At each visit after the Baseline Visit, 
subjects will also be questioned specifically about the status of ongoing AEs. 
Study Endpoints 
Efficacy Endpoints  
Primary  
• 
Improvement in quality of life measured by change from baseline in 
Psychological General Well-Being scale (PGWB) at Week 28 and Week 
52 
Secondary 
• 
Improvement in quality of life measured by change from baseline in 
Psychological General Well-Being scale (PGWB) over time (weeks 4, 8, 
12, 16, 40, 64) 
 
Improvement in quality of life measured by change from baseline in 
Dermatology Life Quality Index (DLQI) over time (weeks 4, 8, 12, 16, 28, 
40, 52, 64) 
 
Proportion of subjects with DLQI score of 0 or 1 at weeks 4, 8, 12, 16, 
28, 40, 52, and 64 
 
Proportion of subjects with DLQI score <5 at weeks 4, 8, 12, 16, 28, 40, 
52, and 64 
 
Proportion of subjects with a reduction of ≥ 5 points in DLQI from 
baseline at weeks 4, 8, 12, 16, 28, 40, 52, and 64 
 
Efficacy of drug as measured by BSA, sPGA, and/or BSAxPGA over 
time (weeks 4, 8, 12, 16, 28, 40, 52, 64) 
 
Efficacy of drug as measured by PASI (% of PASI improvement from 
baseline, absolute PASI) over time (weeks 4,16, 28 and 52) 

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ABBREVIATIONS 
AE 
Adverse event 
BP 
Blood pressure 
BSA 
Body Surface Area 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
DLQI 
Dermatology Life Quality Index 
FDA 
Food and Drug Administration 
hCG 
Human chorionic gonadotropin 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
HR 
Heart Rate 
IB 
Investigator’s Brochure 
ICH-GCP 
International Conference on Harmonization – Good Clinical Practice 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board  
ITT 
Intent-to-treat 
IUD 
Intrauterine Device 
NA, N/A 
Not applicable 
OTC 
Over-the-counter 
PASI 
Psoriasis Area and Severity Index 
PFS 
Pre-filled Syringe 
PP 
Per protocol  
PT 
Preferred Term 
PGWB 
Physical General Well-Being scale 
QoL 
Quality of Life 
RR 
Respiratory Rate 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SOC 
System Organ Class 
sPGA 
Static Physician’s Global Assessment 
TB 
Tuberculosis 
TSQM 
Treatment Satisfaction Questionnaire for Medication 
WOCBP 
Women of childbearing potential 
WPAI-PSO 
Work Productivity and Activity Impairment scale - Psoriasis 
 
 

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TABLE OF CONTENTS   
CLINICAL STUDY PROTOCOL v1.3 ........................................................................... 1 
PROTOCOL APPROVAL ............................................................................................. 3 
STUDY ACKNOWLEDGEMENT .................................................................................. 4 
SUMMARY OF CHANGES .......................................................................................... 5 
PROTOCOL SYNOPSIS .............................................................................................. 9 
SCHEDULE OF STUDY EVENTS ............................................................................. 15 
ABBREVIATIONS ...................................................................................................... 16 
TABLE OF CONTENTS ............................................................................................. 17 
1. 
INTRODUCTION AND RATIONALE ................................................................ 20 
2. 
OBJECTIVES .................................................................................................. 21 
3. 
STUDY DESIGN .............................................................................................. 21 
3.1. 
Number of Subjects ....................................................................................... 21 
3.2. 
Estimated Duration of Study .......................................................................... 21 
4. 
STUDY POPULATION ..................................................................................... 22 
4.1. 
Inclusion Criteria ........................................................................................... 22 
4.2. 
Exclusion Criteria .......................................................................................... 23 
4.3. 
Subject Withdrawal Criteria ........................................................................... 25 
5. 
STUDY INTERVENTION ................................................................................. 26 
5.1. 
Test Article Description ................................................................................. 26 
5.2. 
Formulation, Packaging, Labeling, and Storage ............................................ 26 
5.3. 
Treatment Compliance .................................................................................. 26 
5.4. 
Dispensing .................................................................................................... 27 
5.5. 
Test Article Accountability/Supply Records ................................................... 27 
6. 
PRIOR AND CONCOMITANT THERAPY ........................................................ 28 
6.1. 
Prohibited Medications or Treatments ........................................................... 28 
6.2. 
Allowed Medications or Treatments .............................................................. 29 
7. 
PROCEDURES ................................................................................................ 29 
7.1. 
Visit Activities ................................................................................................ 29 
7.2. 
 29 
7.3. 
...................................................................... 30 
7.4. 
 31 
7.5. 
 ............................................................. 32 
7.6. 
......................................................... 33 
7.7. 
 33 
7.8. 
 34 
7.9. 
 ......................................................... 35 
7.10. 
 36 
7.11. 
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8. 
CLINICAL EVALUATIONS/PRO ASSESSMENTS ........................................... 37 
8.1. 
Body Surface Area (BSA) .............................................................................. 38 
8.2. 
Static Physician’s Global Assessment (sPGA) .............................................. 38 
8.3. 
Psoriasis Area Severity Index (PASI) ............................................................ 38 
8.4. 
Itch Numerical Rating Scale (I-NRS) ............................................................. 38 
8.5. 
Pain Numerical Rating Scale (P-NRS) .......................................................... 39 
8.6. 
Scaling Numerical Rating Scale (S-NRS) ...................................................... 39 
8.7. 
Psychological General Well-Being Index (PGWB) ......................................... 40 
8.8. 
Dermatology Life Quality Index (DLQI) .......................................................... 40 
8.9. 
Work Productivity and Activity Impairment Scale (WPAI-PSO) ...................... 40 
8.10. 
Treatment Satisfaction Questionnaire for Medication (TSQM) ....................... 41 
8.11. 
Tildrakizumab Overall Satisfaction ................................................................ 41 
8.12. 
Patient Happiness with Psoriasis Control ...................................................... 41 
8.13. 
Full-Body Photography (excluding face) ........................................................ 41 
9. 
Laboratory Tests .............................................................................................. 42 
9.1. 
Pregnancy Tests ........................................................................................... 42 
9.2. 
Laboratory Safety Tests ................................................................................ 42 
10. 
END OF STUDY (EOS) CRITERIA .................................................................. 43 
10.1. 
Completion of the Study ................................................................................ 43 
10.2. 
Subject Discontinuation ................................................................................. 43 
10.3. 
Screen Failures ............................................................................................. 44 
11. 
SAFETY ........................................................................................................... 44 
11.1. 
Adverse Events (AE) ..................................................................................... 44 
11.2. 
Serious Adverse Events (SAE) ...................................................................... 49 
11.3. 
Pregnancy ..................................................................................................... 51 
12. 
STATISTICAL CONSIDERATIONS ................................................................. 52 
12.1. 
General Considerations for Data Analysis ..................................................... 52 
12.2. 
Sample Size Determination ........................................................................... 52 
12.3. 
Analysis Populations ..................................................................................... 52 
12.4. 
Statistical Methods ........................................................................................ 52 
13. 
ETHICAL AND REGULATORY CONSIDERATIONS ....................................... 53 
13.1. 
Compliance with Good Clinical Research Practice ........................................ 53 
13.2. 
Institutional Review Board and Informed Consent ......................................... 53 
13.3. 
Protocol Compliance ..................................................................................... 53 
13.4. 
Protocol Revisions ........................................................................................ 54 
13.5. 
Study Monitoring ........................................................................................... 54 
13.6. 
Data Collection Form Requirements.............................................................. 54 
13.7. 
Reports to Institutional Review Board ............................................................ 55 
13.8. 
Quality Assurance Audits .............................................................................. 55 

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13.9. 
Records Retention ........................................................................................ 55 
13.10. Record Confidentiality ................................................................................... 56 
14. 
PUBLICATION POLICY ................................................................................... 56 
15. 
FINANCING AND INSURANCE ....................................................................... 57 
16. 
REFERENCES ................................................................................................ 58 
17. 
APPENDIX A: ELEMENTS OF INFORMED CONSENT .................................. 60 
18. 
APPENDIX B: STATIC PGA SCORE SCALES ................................................ 62 
19. 
APPENDIX C: PSORIASIS AREA SEVERITY INDEX ..................................... 64 
20. 
APPENDIX D: PSYCHOLOGICAL GENERAL WELL-BEING INDEX ............... 66 
21. 
APPENDIX E: DERMATOLOGY LIFE QUALITY INDEX .................................. 73 
22. 
APPENDIX F: WORK PRODUCTIVITY AND ACTIVITY IMPAIRMENT 
QUESTIONNAIRE: PSORIASIS (WPAI:PSO) .................................................. 75 
23. 
APPENDIX G: TREATMENT SATISFACTION QUESTIONNAIRE FOR 
MEDICATION (TSQM) Version 1.4 .................................................................. 77 

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1. 
INTRODUCTION AND RATIONALE  
 
Psoriasis is a chronic, disfiguring, immune-mediated skin disease, with recent estimates 
of the global prevalence in adults ranging from 0.51% to 11.43%.1 Plaque psoriasis is the 
most common form, affecting approximately 80% to 85% of psoriasis patients, and 
appears as sharply demarcated, red lesions of variable size usually covered with 
silver/white scales.  Lesions are typically itchy and painful. The severity of plaque 
psoriasis is moderate-to-severe in an estimated 18% of patients in the U.S. suffering from 
plaque psoriasis.2  Biologic agents have greatly enhanced the treatment options of 
subjects with moderate-to-severe chronic plaque psoriasis who are candidates for 
phototherapy or systemic therapy.  Currently approved biologics  include tumor necrosis 
factor (TNF) antagonist agents, i.e., etanercept (Enbrel®), infliximab (Remicade®), and 
adalimumab (Humira®), the interleukin [IL]-12 and IL-23p40 antagonist ustekinumab 
(Stelara®), IL-17 antagonist agents, i.e., secukinumab (Cosentyx®), brodalumab (Siliq®) 
ixekizumab (Taltz®), and IL-23 antagonists guselkumab (Tremfya®) and tildrakizumab 
(Ilumya®). 
The physical effects of psoriasis are accompanied by a significant and potentially lasting 
impact on the emotional and psychosocial well-being of patients, and may lead to 
substantial burden in terms of disability or psychosocial stigmatization.3,4  Significant loss 
of productivity and adverse effects on mental well-being result in negative effects not only 
on individuals but also on society.5,6  A recent systematic literature review revealed that 
psoriasis patients suffer from the same deterioration in health-related quality of life as 
patients with other major medical diseases, including cancer and cardiovascular 
diseases.7   
Tildrakizumab, a humanized monoclonal antibody which selectively binds to the p19 
subunit of IL-23, was recently approved in the U.S. for patients with moderate-to-severe 
plaque psoriasis.  
 
 
 
 
 
  
 
 
 
 
 

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“Quality of life” refers to the general well-being of individuals and their ability to enjoy 
normal life activities, encompassing satisfaction with physical and psychological health, 
social and sexual relationships, and employment.  It is important to assess patient-
reported quality of life outcomes in addition to physician-assessed physical parameters 
to truly characterize and assess the burden of psoriasis and response to treatment from 
the patient’s point of view.  This study seeks to assess the longer-term impact of 
tildrakizumab on improvements in HRQoL using multiple assessment scales, as well as 
assessment of psoriasis symptom control and long-term efficacy and safety, under real 
world conditions. 
Detailed information regarding the safety and tolerability of tildrakizumab can be found in 
the Investigator's Brochure and package labeling. 
 
2. 
OBJECTIVES 
The primary objective is to demonstrate improvement from baseline in patient quality of 
life (QOL) after 28 and 52 weeks of treatment with tildrakizumab, under real world 
conditions, as measured by Psychological General Well-Being scale (PGWB). 
Secondary objectives include assessment of patient quality of life as measured by the 
Dermatology Life Quality Index (DLQI), work productivity and activity impairment, 
psoriasis symptom control, patient satisfaction, long-term efficacy and safety.   
3. 
STUDY DESIGN 
This is a Phase 4 multicenter, uncontrolled open-label study design. There will be a total 
of 10 study visits at Screening, Baseline, Week 4, Week 8, Week 12, Week 16, Week 28, 
Week 40, Week 52 and Week 64, with subjects receiving tildrakizumab injections at Week 
0, Week 4, Week 16, Week 28, Week 40, and Week 52.  The total study duration will be 
approximately 64 weeks, excluding a screening period. 
3.1. 
Number of Subjects 
Approximately 60 subjects will be enrolled into the study at two sites.   
3.2. 
Estimated Duration of Study 
For an individual subject, the study duration should be approximately 64                      
weeks. The duration of the study as a whole will vary based upon the rate of recruitment 
and completion of subjects. 
 

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4.2. Exclusion Criteria 
A subject is ineligible to enter the study if he/she meets one or more of the following 
criteria: 
1. Subject is pregnant, lactating, or is planning to become pregnant during the 
study. 
2. Subject is younger than 18 years of age. 
  
 
 

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7. Subjects with uncontrolled mental illness or active suicidal ideations based on 
mental health questionnaire of choice. 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
  
 
 
 
 
 
 
 
 
 
18. Subject is known, or suspected of being unable to comply with the study protocol, 
in the opinion of the investigator. 
19. Subject is currently enrolled in an investigational drug or device study. 
 
 
  
 
 
  

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4.3. Subject Withdrawal Criteria 
Treatment for a subject can be discontinued at any time, if in the opinion of the medical 
monitor, there are any clinically significant events at any visit that may impact the safety 
of subject(s). A subject must be discontinued from study medication if either of the 
following occur: 
• A serious adverse event, drug reaction or complication, or an unacceptable 
adverse event 
 whether attributed to study medication or 
not, that precludes continuation of treatment with study medication. This includes 
the development of allergic reactions or the development of other potentially 
serious drug reactions to medication required by the protocol. 
 
• Pregnancy: A subject who becomes pregnant during the study must discontinue 
study medication immediately. 
In the event that a subject will not receive subsequent treatment (ie, due to safety 
concerns or refusal), subject will be encouraged to participate in follow-up visits so that 
safety responses can be monitored.   However, subject may withdraw from the study at 

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any time for any reason.  Procedures for handling subjects who withdraw from the study 
are described in Section 10.2.  
 
5. 
STUDY INTERVENTION 
The investigator acknowledges that the test article must be used strictly in accordance 
with the protocol and only by the investigator and sub-investigators listed on the FDA 
Form 1572.  A sponsor representative will be at the site to inventory drug.  The 
investigator must maintain adequate records documenting the receipt and dispensation 
of all study supplies.  Sponsor will supply forms to record the date drug was received, lot 
number and a dispensing record to record each subject use. 
5.1. Test Article Description 
Tildrakizumab is a humanized IgG1/k antibody that specifically binds to the p19 subunit 
of interleukin-23 (IL-23). Tildrakizumab injection, 
 is a sterile, clear 
to slightly opalescent, colorless to slightly yellow solution. Tildrakizumab 100 mg/mL in 1 
mL pre-filled syringes (PFS) will be provided by the Sponsor.   
5.2. Formulation, Packaging, Labeling, and Storage 
Each 1 mL single-dose PFS contains 100 mg of tildrakizumab formulated in:
 
 
   
 
 
Test article will be affixed with a clinical label in accordance with regulatory requirements.  
Test article must be stored in a secure, limited-access location under the following storage 
conditions:  
• Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from 
light until the time of use.  
• Do not freeze.  
• Do not shake.  
 
Site storage conditions should be monitored by the site personnel for adherence to label 
specifications and reviewed during site visits. 
5.3. Treatment Compliance 
Test article will be administered by qualified members of the study staff at the 
investigator’s site. 

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5.4. Dispensing 
The study staff should assign the subject numbers in ascending order beginning with the 
lowest available subject number. 
The investigator or qualified designee(s) will dispense test article to subjects who have 
provided written informed consent and have met the entry criteria. Clinical supplies may 
not be used for any purpose other than that which is stated in this protocol.  
See the Schedule of Study Events for a schedule of when test article is to be dispensed 
to the subjects. 
5.5. Test Article Accountability/Supply Records 
It is the responsibility of the investigator to ensure that a current record of test article 
disposition is maintained.  Accurate and current accounting of the dispensing of test 
article will be maintained on an ongoing basis by a member of the site staff; test article 
dispensed to the site and administered to each subject will be recorded on an 
Accountabiity Log.  Accountability records or logs must comply with applicable regulations 
and guidelines, and should include: 
 
• Amount received placed in storage area.  
• Amount currently in storage area.  
• Lot or batch number.  
• Dates and initials of the person responsible for each product inventory  
entry/movement.  
• Amount dispensed to each subject, including unique subject identifiers.  
• Amount transferred to another area for dispensing or storage.  
• Non-study disposition (e.g., lost, wasted, broken).  
• Amount returned to sponsor.  
• Amount destroyed at study site, if applicable.  
Sponsor or designee will provide forms to facilitate inventory control if the staff at the 
study site does not have an established system that meets these requirements. 
The Accountability Log will be verified by the sponsor's monitor. The original 
Accountability Log will be approved by the investigator and retained at the site and a copy 
supplied to the sponsor when the study is complete. 
Any device administered by site staff in the study which is felt to be defective, should be 
returned to the sponsor for inspection and follow-up. Specific procedures on the handling 

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and return of defective devices will be provided in a separate procedures manual for this 
study. 
In the event the investigational products destruction is arranged by the site, copies of the 
destruction records should be returned to the sponsor.  
The sponsor’s monitor will instruct the site on the return of all investigational product 
supplies. A final inventory of the total amount of investigational products received at the 
study site against the amount used and returned must be recorded in the Accountability 
Log. Inventory records must be readily available for inspection by the study monitor and/or 
auditor, and open to government inspection at any time. 
6. 
PRIOR AND CONCOMITANT THERAPY 
Current medications and any medications taken in the 12 weeks prior to Visit 1 
(Screening) will be recorded as prior/concomitant medications with the corresponding 
indication.  The medications to be recorded include prescription and over-the-counter 
medications (except vitamins and dietary supplements).  All medications taken on a 
regular basis should be recorded on the CRFs prior to commencing use of the test article. 
Therapies (medication and non-medication therapies) not restricted by the protocol may 
be used during the study for the treatment or prevention of disease or to maintain good 
health.  Vitamins and mineral supplements are permitted at dosages considered by the 
investigator as reasonable for maintaining good health.  Non-prohibited chronic therapies 
being used prior to Visit 1 may be continued.  Any changes in concomitant therapies 
during the study must be recorded on the CRFs.  The reason for any change in 
concomitant medications or therapies/procedures should be reported and should reflect 
either a baseline medical condition documented in the medical history of the CRF or an 
AE. 
6.1. Prohibited Medications or Treatments 
Include medications within the following categories: 
• Products used within the specified time frames, as specified in Section 4.2. 
• Treatment with a biological agent other than test article (including monoclonal 
antibodies, alefacept) 
• Any investigational agents (other than test article) 
• New treatments for psoriasis that subject was not using consistently prior to 
screening 
 

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6.2. Allowed Medications or Treatments 
• Topical steroids, phototherapy, or other systemic agents at the same 
strength/dosage that was being used consistently prior to screening, as deemed 
appropriate by the study investigators 
• Medications needed to treat pre-existing medical conditions that are not 
exclusionary to the study 
• Medications necessary to treat adverse events or medical emergencies 
• Vitamins, supplements and other over the counter (OTC) medications 
 
The use of concomitant medication/treatment must be recorded on the CRFs and must 
relate to the documented medical history, prophylaxis, or an adverse event. 
7. 
PROCEDURES 
Refer to the Study Schedule of Events for a summary of procedures at each visit. 
The timing of each visit is relative to Day 1 (Visit 2), which is defined as baseline. 
All visits should be performed within the windows specified in the Study Schedule of 
Events. Every attempt should be made to have each subject attend each visit as 
scheduled. However, if a subject is unable to attend a visit within the specified windows, 
the visit should be scheduled as closely as possible to these windows. If the subject is 
unable to attend a dosing visit within the specified windows, the investigator or qualified 
designee should discuss appropriate dosing with the medical monitor (or appropriate 
designee). A subject should not miss a protocol-specified visit due to scheduling 
difficulties. 
7.1. Visit Activities 
 
Screening procedures should be completed within 30 days prior to the baseline visit 
(Day 1).  The following screening procedures are to be performed: 
• Review study information with the subject and obtain written informed consent, 
including whether they are willing to be contacted by a representative of the 
sponsor to share their experience, prior to any performing any procedures. 
• Obtain demographic information 
• Medical history, including psoriasis treatment history. 
 
 
 
 

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o Psychological General Well-Being scale (PGWB) 
o Dermatology Life Quality Index (DLQI) 
• Additional subject questionnaires 
o Itch Numerical Rating Scale  
o Pain Numerical Rating Scale  
o Scaling Numerical Rating Scale 
o Patient happiness with psoriasis control  
o Work Productivity and Activity Impairment scale (WPAI-PSO) 
 
• Limited physical examination, including psoriasis assessments.   
o Weight 
o Vital signs: temperature, blood pressure, heart rate, and respiratory rate 
o Body Surface Area (BSA)  
o Static Physician’s Global Assessment (sPGA) 
o Psoriasis Area Severity Index (PASI) 
• Full-body photography (excluding face) 
• Urine Pregnancy Test (if applicable) 
o Urine pregnancy tests must have a minimum sensitivity of 25 mIU β-hCG/ml 
• Test article injection 
• Record adverse events, concurrent procedures and changes in concomitant 
medications 
• Schedule 
 
  
Perform the following: 
• Quality of Life (QOL) assessments 
o Psychological General Well-Being scale (PGWB) 
o Dermatology Life Quality Index (DLQI) 
• Additional subject questionnaires 
o Itch Numerical Rating Scale  
o Pain Numerical Rating Scale  
o Scaling Numerical Rating Scale 
o Tildrakizumab Overall Satisfaction Numerical Rating Scale 
 symptom control, safety, etc 

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o Static Physician’s Global Assessment (sPGA) 
• Record adverse events, concurrent procedures and changes in concomitant 
medications 
• Schedule 
 
  
Perform the following: 
• Quality of Life (QOL) assessments 
o Psychological General Well-Being scale (PGWB) 
o Dermatology Life Quality Index (DLQI) 
• Additional subject questionnaires 
o Itch Numerical Rating Scale  
o Pain Numerical Rating Scale  
o Scaling Numerical Rating Scale 
o Tildrakizumab Overall Satisfaction Numerical Rating Scale 
 symptom control, safety, etc 
o Patient happiness with psoriasis control  
o Treatment Satisfaction Questionnaire for Medication (TSQM) 
 
• Limited physical examination, including psoriasis assessments.   
o Weight 
o Vital signs: temperature, blood pressure, heart rate, and respiratory rate 
o Body Surface Area (BSA)  
o Static Physician’s Global Assessment (sPGA) 
o  
• Record adverse events, concurrent procedures and changes in concomitant 
medications 
• Schedule 
 
  
Perform the following: 
• Quality of Life (QOL) assessments 
o Psychological General Well-Being scale (PGWB) 
o Dermatology Life Quality Index (DLQI) 

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• Additional subject questionnaires 
o Itch Numerical Rating Scale  
o Pain Numerical Rating Scale  
o Scaling Numerical Rating Scale 
o Tildrakizumab Overall Satisfaction Numerical Rating Scale 
 symptom control, safety, etc 
o Patient happiness with psoriasis control  
o Treatment Satisfaction Questionnaire for Medication (TSQM) 
o Work Productivity and Activity Impairment scale (WPAI-PSO) 
 
• Limited physical examination, including psoriasis assessments.   
o Weight 
o Vital signs: temperature, blood pressure, heart rate, and respiratory rate 
o Body Surface Area (BSA)  
o Static Physician’s Global Assessment (sPGA) 
o Psoriasis Area Severity Index (PASI) 
• Full-body photography (excluding face) 
• Urine Pregnancy Test (if applicable) 
o Urine pregnancy tests must have a minimum sensitivity of 25 mIU β-hCG/ml 
o  
• Test article injection 
• Record adverse events, concurrent procedures and changes in concomitant 
medications 
• Schedule 
 
  
Perform the following: 
• Quality of Life (QOL) assessments 
o Psychological General Well-Being scale (PGWB) 
o Dermatology Life Quality Index (DLQI) 
• Additional subject questionnaires 
o Itch Numerical Rating Scale  
o Pain Numerical Rating Scale  
o Scaling Numerical Rating Scale 

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o Tildrakizumab Overall Satisfaction Numerical Rating Scale 
 symptom control, safety, etc 
o Patient happiness with psoriasis control  
o Treatment Satisfaction Questionnaire for Medication (TSQM) 
o Work Productivity and Activity Impairment scale (WPAI-PSO) 
• Limited physical examination, including psoriasis assessments.   
o Weight 
o Vital signs: temperature, blood pressure, heart rate, and respiratory rate 
o Body Surface Area (BSA)  
o Static Physician’s Global Assessment (sPGA)  
o Psoriasis Area Severity Index (PASI) 
• Full-body photography (excluding face) 
• Urine Pregnancy Test (if applicable) 
o Urine pregnancy tests must have a minimum sensitivity of 25 mIU β-hCG/ml 
o  
• Test article injection 
• Record adverse events, concurrent procedures and changes in concomitant 
medications 
• Schedule
 
  
Perform the following: 
• Quality of Life (QOL) assessments 
o Psychological General Well-Being scale (PGWB) 
o Dermatology Life Quality Index (DLQI) 
• Additional subject questionnaires 
o Itch Numerical Rating Scale  
o Pain Numerical Rating Scale  
o Scaling Numerical Rating Scale 
o Tildrakizumab Overall Satisfaction Numerical Rating Scale 
 symptom control, safety, etc 
o Patient happiness with psoriasis control  
o Treatment Satisfaction Questionnaire for Medication (TSQM) 
o Work Productivity and Activity Impairment scale (WPAI-PSO) 
 

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• Limited physical examination, including psoriasis assessments.   
o Weight 
o Vital signs: temperature, blood pressure, heart rate, and respiratory rate 
o Body Surface Area (BSA)  
o Static Physician’s Global Assessment (sPGA) 
• Urine Pregnancy Test (if applicable) 
o Urine pregnancy tests must have a minimum sensitivity of 25 mIU β-hCG/ml 
• Test article injection 
• Record adverse events, concurrent procedures and changes in concomitant 
medications 
• Schedule 
 
 
 
Perform the following: 
• Quality of Life (QOL) assessments 
o Psychological General Well-Being scale (PGWB) 
o Dermatology Life Quality Index (DLQI) 
• Additional subject questionnaires 
o Itch Numerical Rating Scale  
o Pain Numerical Rating Scale  
o Scaling Numerical Rating Scale 
o Tildrakizumab Overall Satisfaction Numerical Rating Scale 
 symptom control, safety, etc 
o Patient happiness with psoriasis control  
o Treatment Satisfaction Questionnaire for Medication (TSQM) 
o Work Productivity and Activity Impairment scale (WPAI-PSO) 
 
• Limited physical examination, including psoriasis assessments.   
o Weight 
o Vital signs: temperature, blood pressure, heart rate, and respiratory rate 
o Body Surface Area (BSA)  
o Static Physician’s Global Assessment (sPGA)  
o Psoriasis Area Severity Index (PASI) 
• Full-body photography (excluding face) 
• Urine Pregnancy Test (if applicable) 

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o Urine pregnancy tests must have a minimum sensitivity of 25 mIU β-hCG/ml 
• Test article injection 
• Record adverse events, concurrent procedures and changes in concomitant 
medications 
 
  
Perform the following: 
• Quality of Life (QOL) assessments 
o Psychological General Well-Being scale (PGWB) 
o Dermatology Life Quality Index (DLQI) 
• Additional subject questionnaires 
o Itch Numerical Rating Scale  
o Pain Numerical Rating Scale  
o Scaling Numerical Rating Scale 
o Tildrakizumab Overall Satisfaction Numerical Rating Scale 
 symptom control, safety, etc 
o Patient happiness with psoriasis control  
o Treatment Satisfaction Questionnaire for Medication (TSQM) 
o Work Productivity and Activity Impairment scale (WPAI-PSO) 
 
• Limited physical examination, including psoriasis assessments.   
o Weight 
o Vital signs: temperature, blood pressure, heart rate, and respiratory rate 
o Body Surface Area (BSA)  
o Static Physician’s Global Assessment (sPGA) 
• Urine Pregnancy Test (if applicable) 
o Urine pregnancy tests must have a minimum sensitivity of 25 mIU β-hCG/ml 
• Record adverse events, concurrent procedures and changes in concomitant 
medications 
• Complete EOS form 
8. 
CLINICAL EVALUATIONS/PRO ASSESSMENTS 
The following clinical evaluations will be performed according to the Schedule of Study 
Events and Section 7.1. The same investigator should complete the evaluations for a 

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8.7. Psychological General Well-Being Index (PGWB) 
The PGWB is a self-administered validated psychometric instrument that measures a 
person's emotional well-being.12 It is specifically designed to be suitable for assessing 
psychological well being in the general medical population as opposed to a psychiatric 
population. The 22 questions of the PGWB 
 
 
is graded on a Likert scale, which is commonly used in psychometric questionnaires 
where the answers range from strongly agree to strongly disagree with gradations in 
between. Total scores range from 0 to 110, with higher scores indicating better 
psychological well being. This instrument has been validated and used in many countries 
on large samples of the general population and on various subsets of medical patients.  
 
8.8. Dermatology Life Quality Index (DLQI) 
The DLQI is a self-administered and user-friendly validated questionnaire used to 
measure the health-related quality of life of adult patients suffering from a skin disease.13 
It consists of 
 questions concerning patients’ perception of the impact of skin diseases 
on different aspects of their health related quality of life over the last week. It has been 
validated for adult dermatology patients aged 16 years and older. 
 
 
  
 
 
  
  
 higher scores mean 
greater impairment of patient’s QoL.  
 
 
 
8.9. Work Productivity and Activity Impairment Scale (WPAI-PSO) 
The WPAI is a validated, subject-reported quantitative assessment of the amount of 
absenteeism, presenteeism and daily activity impairment attributable to general health or 
a specific health problem.14 The WPAI has been validated to specifically quantify work 
impairments for numerous diseases and the WPAI:PSO was created specifically for 
administering to patients with psoriasis.15 WPAI surveys were analyzed based on 

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captured.  Subjects who refuse to undergo full-body photography may still be enrolled in 
the study. 
9. 
Laboratory Tests 
9.1. Pregnancy Tests 
A serum pregnancy test must be performed on all female subjects of child-bearing 
potential at Visit 1.  A UPT will be performed in women of childbearing potential at all visits 
where study article is administered.  The UPT used must have a minimum sensitivity of 
25mIU of β-hCG/mL of urine.  Please see Schedule of Study Events for all subsequent 
UPTs.  The investigator will report the UPT results on the CRFs, in the subject’s medical 
records and in any independent records maintained at the study site. Subjects with a 
positive pregnancy test at Visit 1 or prior to the first dose of test article will not be allowed 
to enter the study (screen failure).  Subjects with a positive pregnancy test any time after 
the first dose of test article will not receive further test article; however subjects should 
continue with non-treatment follow-up visits.  All pregnancies should be immediately 
reported to the medical monitor and followed through to resolution (i.e., delivery, 
miscarriage, or abortion).  The report should be submitted within the 24 hours of 
knowledge. 
9.2. Laboratory Safety Tests 
Laboratory tests for hematology, blood chemistry, and virology/HIV 
 
Blood samples for laboratory tests are to be taken prior to first administration of test 
article and should be performed according to standard laboratory procedures. Followup 
labs for chemistry, blood count and virology beyond screening can be done at the clinical 
judgment of the investigator. 
 
 

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• AEs  
• Worsening of condition or treatment failure (in the opinion of the investigator)  
• Intercurrent illness which may, in the investigator’s opinion, significantly affect 
assessment of clinical status 
• Noncompliance  
• Lost to follow-up  
• Sponsor administrative reasons  
If a subject withdraws prematurely during the treatment period, complete the CRF for the 
appropriate visit, then complete the End of Study CRFs. 
10.3. 
Screen Failures 
If a subject is a screen failure at Visit 1, complete the Screen Failure CRF. 
11. SAFETY 
11.1. 
Adverse Events (AE) 
An adverse event (AE) is defined as any untoward medical occurrence associated with 
the use of a drug in humans, whether or not considered drug related.  An AE can therefore 
be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of the drug without any judgment 
of causality. 
Information on the medical condition of subjects should begin following the subject’s 
written consent to participate in the study and a medical history should be taken at 
screening. During any wash out and baseline periods, any changes in the health of 
subjects should be recorded as changes in medical history unless an event occurred as 
a result of a study-related procedure and is unanticipated; where in such cases, the event 
should be recorded as an adverse event and reported to the Institutional Review Board 
(IRB) as an “unanticipated problem” in accordance with local procedures. Other changes 
in subject health information becomes AE data when the subject begins dosing with the 
test article and therefore AE data should be collected from the date of the first dose of 
test article. These data are considered treatment-emergent AEs. 
Timely and complete reporting of all AEs assists the Sponsor in identifying any untoward 
medical occurrence, thereby allowing:  
1) protection of the safety of study subjects;  
2) a greater understanding of the overall safety profile of the test article;  
3) recognition of dose-related test article toxicity;  

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4) appropriate modification of study protocols;  
5) improvements in study design or procedures; and  
6) adherence to worldwide regulatory requirements.  
AEs may be either spontaneously reported or elicited during questioning and examination 
of a subject. The investigator will instruct the subject to report any adverse events that 
may occur during the study. At each visit, the investigator should ask the subject, in non-
directive fashion, about any change in the subject’s overall condition since the previous 
visit. If known, the investigator should report the diagnosis of the underlying illness or 
disorder, rather than its individual symptoms.  
All AEs must be completely recorded on the AE CRF and include the following: 
• Date of onset  
• Location of the event – specify whether within affected region 
• The Severity of the event. Record the maximum intensity taking into account the 
possible range of the intensity of the event, using the following definitions: 
 
 

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SEVERITY 
Mild 
Adverse event noticeable by the subject but did not interfere in a significant manner with 
the subject’s normal functioning; remedial therapy may have been given. 
Moderate 
The adverse event was sufficiently intense to produce some impairment of functioning; 
remedial therapy may have been given. 
Severe 
The adverse event produced a significant impairment of functioning or incapacitation; 
therapy was needed. 
 
• Categorize the Relationship to Study Treatment  of the AE, as defined below: 
RELATIONSHIP 
Not  
Related: 
Concomitant illness, caused by other drug, procedure, accident or event with 
no reasonable association with treatment. 
Unlikely: 
An event that does not follow a reasonable temporal association sequence from 
administration of the test article; that does not follow a known or expected 
response pattern to the test article, or most likely was caused by the subject’s 
clinical state, other drug, procedure, or other causes, because of their known 
effects. 
Possibly: 
An event that follows a reasonable temporal sequence from administration of 
the test article; follows a known or expected response pattern to the test article; 
but may have been produced by the subject’s clinical state or by other drugs or 
procedures administered to the subject, or by other causes. 
Probably: 
An event that follows a reasonable temporal sequence from administration of 
test article; follows a known or expected response pattern to the test article; is 
confirmed by improvement on stopping or reducing the dosage; cannot be 
reasonably explained by the known characteristics of the subject’s clinical state 
or other drugs, procedures or other causes. 
Definite: 
An event that follows a reasonable temporal sequence from administration of 
test article; follows a known or expected response pattern to the test article; is 
confirmed by improvement on stopping or reducing the dosage, and 
reappearance of the event on repeat exposure (rechallenge). 
 
• Determine the Action Taken with Study Treatment due to the AE using the 
definitions below: 

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Subjects experiencing AEs that cause interruption or discontinuation of test article, or 
those experiencing AEs that are present at the end of their participation in the study 
should receive follow-up as appropriate. If possible, report the outcome of any AE that 
caused permanent discontinuation or that was present at the end of the study particularly 
if the AE is considered by the investigator to be treatment-related (i.e., definitely, probably, 
or possibly related to test article). 
 
• Determine if the event is considered Serious based on the definitions in Section 
11.2. 
• Record whether the event caused Study Discontinuation. 
 
An adverse reaction is any AE caused by a drug. Adverse reactions are a subset of all 
suspected adverse reactions for which there is reason to conclude that the drug caused 
the event. For the purposes of prescription drug labeling, the term adverse reaction 
means an undesirable effect, reasonably associated with the use of a drug that may occur 
as part of its pharmacological action or may be unpredictable in its occurrence.  
A suspected adverse reaction is any adverse event for which there is a reasonable 
possibility that the drug caused the event.  
For the purposes of IND safety reporting, “reasonable possibility” means there is evidence 
to suggest a causal relationship between the drug and the adverse event. A suspected 
adverse reaction implies a lesser degree of certainty about causality than adverse 
reaction, which means any adverse event caused by a drug.  
An adverse event or suspected adverse reaction is considered “unexpected” if it is not 
listed in the investigator brochure or is not listed at the specificity or severity that has been 
observed; or, if an investigator brochure is not required or available, is not consistent with 
the risk information described in the general investigational plan or elsewhere in the 
current application. For example, under this definition, hepatic necrosis would be 
unexpected (by virtue of greater severity) if the investigator brochure referred only to 
elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral 
vasculitis would be unexpected (by virtue of greater specificity) if the investigator brochure 
listed only cerebral vascular accidents. "Unexpected," as used in this definition, also 
refers to adverse events or suspected adverse reactions that are mentioned in the 
investigator brochure as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug, but are not specifically mentioned as occurring 
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11.2. 
Serious Adverse Events (SAE) 
An assessment of the seriousness and causality of the event will be made by  the 
investigator, the medical monitor and the Sponsor’s pharmacovigilance (PV) department.  
The investigator is to complete a special form provided by the Sponsor in the case of a 
SAE; expeditious handling is required to comply with regulatory requirements.  SAEs will 
also be recorded on the AE CRF.   
An SAE is classified as any untoward medical occurrence which at any dose 
• Results in death 
• Is life-threatening 
• Requires in-patient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant incapacity or substantial disruption of the 
ability to conduct life functions 
• Is a congenital anomaly/ birth defect 
• Is an important medical event(s) that may not be immediately life-threatening or 
result in death or hospitalization but, based upon appropriate medical judgement, 
may jeopardize the subject or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the definition above.  These should 
also be considered serious.   
Events NOT considered to be serious adverse events are: 
• Hospitalizations for the treatment, which was elective or pre-planned, of a pre-
existing condition that did not worsen, and 
• Treatment on an emergency, outpatient basis, for an event not fulfilling any of the 
definitions of “serious” given above and not resulting in hospital admission.  
 
The investigator should take appropriate diagnostic and therapeutic measures to 
minimize the risk to the subject.  Where appropriate, the investigator should take 
diagnostic measures to collect evidence for clarification of the relationship between the 
SAE and the investigational product. 
Adverse events classified as “serious” by either the investigator or the Sponsor require 
expeditious handling and reporting to the Sponsor to comply with regulatory 
requirements. All serious AEs, whether related or unrelated to test article, must be 
immediately reported no later than 24 hours of receipt by telephone to the Medical 
Monitor, the Sponsor’s PV department via email 
 
and, in the event that the Medical Monitor is unavailable, to the Project Manager 
listed on the first page of the protocol. Written notification of all SAEs should be sent 

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to the Medical Monitor/Project Manager and the Sponsor’s PV department by email or 
confirmed facsimile transmission. These include those SAEs listed in the protocol or 
investigator brochure and must include an assessment of whether there is a reasonable 
possibility that the drug caused the event.  
If only limited information is initially available, follow-up reports are required. Should the 
investigator become aware of a SAE (regardless of its relationship to test article) that 
occurs within 30 days after stopping the test article, the SAE must be reported in 
accordance with procedures specified in this protocol. In the event of death, if an autopsy 
is performed, a copy of the report should be sent to the Sponsor, if available.  
As required, the Sponsor will notify participating investigators of all suspected adverse 
reactions that are serious and unexpected. This notification will be in the form of an IND 
safety report of potential serious risks as soon as possible but no later than 15 calendar 
days after the Sponsor determines that the information is “reportable” according to the 
criteria listed in 21 CFR Section 312.32. These are:  
i) Serious and unexpected suspected adverse reactions,  
ii) Findings from other studies including epidemiological studies, pooled analyses 
or other clinical studies that suggest a significant risk in humans exposed to the 
test articles,  
iii) Findings from animal or in vitro tests that suggest a significant risk to humans 
exposed to the test articles, or reports of significant organ toxicity at or near the 
expected human exposure, and  
iv) Clinically important increases in the rate of occurrence of serious suspected 
adverse reactions.  
Upon receiving such notices, the investigator must review and retain the notice with the 
Investigator Brochure and immediately submit a copy of this information to the 
responsible IRB according to local regulations. The investigator and IRB will determine if 
the informed consent requires revision. The investigator should also comply with the IRB 
procedures for reporting any other safety information. Where required, submission of 
safety updates by the investigator to Health Authorities should be handled according to 
local regulations.  
 
The IRB may require the investigator to report serious adverse events that are possibly 
related to the study drug or all serious adverse events regardless of relatedness. The IRB 
requirements should be reviewed carefully. The investigator is responsible to notify the 
IRB of specific adverse event information as specified in the IRB approval. 

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11.3. 
Pregnancy 
Before enrolling women of childbearing potential in this clinical study, investigators must 
review the following information about study participation for women: 
o Informed consent requirements 
o Contraceptives in current use 
o Drug interactions with hormonal contraceptives 
o Guidelines for the follow-up of a reported pregnancy in this clinical study. 
All female subjects of child-bearing potential must agree to use a highly effective form of 
birth control (See Section 4) during the course of the study in a manner such that risk of 
failure is minimized. Prior to study enrollment, all female subjects of child-bearing 
potential must be advised of the importance of avoiding pregnancy during study 
participation and the potential risk factors for an unintentional pregnancy. Following 
review of this information and appropriate subject counseling, the investigator or designee 
and the subject must sign the informed consent.   
If pregnancy is confirmed during screening, the subject must not receive test article and 
must not be enrolled in the study. All females of childbearing potential enrolling into the 
study must have pregnancy testing prior to each administration of test article. The test 
article administration must be withheld until the result of pregnancy testing is known.  
During the study, all female subjects should be instructed to contact the investigator 
immediately if they suspect they might be pregnant (e.g., missed or late menstrual 
period). If pregnancy is confirmed, the subject must not receive further study therapy; 
however every effort should be made to retain the subject in the study and complete all 
follow-up visits.  At a minimum, the subject must be followed for safety. 
The Investigator must immediately notify the Medical Monitor and IRB of any pregnancy 
associated with the study therapy, maintain careful source documentation and record the 
event on the appropriate CRF and pregnancy surveillance form.  Protocol-required 
procedures (except for administration of test article) for pregnant subjects must be 
performed on the subject unless contraindicated by pregnancy (e.g., x-ray studies).  Other 
appropriate follow-up procedures including counseling of the subject by the investigator 
and her obstetrician should be considered, if appropriate.  In addition, the Investigator 
must report any follow-up information to the Medical Monitor and the IRB regarding the 
course of the pregnancy, including perinatal and neonatal outcome on the pregnancy 
surveillance form provided.  Although pregnancy itself is not an adverse event, any 
complications during pregnancy should be recorded as AEs (or SAEs – if they fulfill the 
SAE criteria). Abortion, whether accidental, therapeutic or spontaneous should be 
reported as a SAE. Infants should be followed for a minimum of 8 weeks or as required 
by the IRB or local law, whichever is longer.  Any congenital anomaly/birth defect in a 

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child born to a subject exposed to test article should be recorded as a SAE and details 
documented on the pregnancy surveillance form. 
12. STATISTICAL CONSIDERATIONS 
12.1. 
General Considerations for Data Analysis 
The methodology presented below is a summary of the more detailed analysis plan that 
will be presented in the Statistical Analysis Plan (SAP).  The SAP will be finalized before 
the database is locked.  Any changes to the methods described in the final SAP will be 
described and justified in the clinical study report. 
It is planned that the data from both centers that participate in this protocol will be 
combined so that an adequate number of subjects will be available for analysis. 
All statistical analyses will be performed using SAS statistical software. 
12.2. 
Sample Size Determination 
No formal sample size calculations were performed.  The sample size of 60 subjects was 
selected to provide adequate estimates of probably events in the population.   
12.3. 
Analysis Populations 
Efficacy will be investigated in 2 populations.  The PP population will comprise all subjects 
who are enrolled and receive all doses of the study medication, have no major study 
protocol violations and do not use any prohibited medications during the study period.  
The ITT population will comprise all subjects who are enrolled and assigned to receive 
the study medication.  The safety population will comprise all subjects who are enrolled 
and receive at least one dose of the study medication. 
 
 
 
12.4. 
Statistical Methods 
All population characteristics and parameters will be described using summary statistics.  
Categorical variables will be summarized using frequency counts and percentages.  
Descriptive statistics (n, mean, standard deviation [SD], median, minimum, and 
maximum) will be calculated for each continuous variable.  Estimates of the efficacy 
endpoints of interest will be calculated with 
 wherever 
possible.  
 
 

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Adverse events will be presented in data listings and summarized by frequency and 
severity. 
13. ETHICAL AND REGULATORY CONSIDERATIONS 
13.1. 
Compliance with Good Clinical Research Practice 
This study will be conducted in compliance with the principles of the Declaration of 
Helsinki, with the current Good Clinical Practice guidelines and with other applicable 
regulations. The investigator and all study staff will conduct the study in compliance with 
this protocol. The protocol, informed consent documents, recruitment advertisements and 
any amendments to these items will have IRB approval prior to study initiation. Voluntary 
informed consent will be given by every subject prior to the initiation of any study-related 
procedures. Subjects must provide written consent. The rights, safety and well-being of 
the study subjects are the most important considerations and prevail over the interests of 
science and society. All personnel involved in the conduct of this study must be qualified 
by education, training and experience to perform their assigned responsibilities. 
13.2. 
Institutional Review Board and Informed Consent 
Before study initiation, the investigator must have written and dated approval from the 
IRB for the protocol, consent form, subject recruitment materials/process (e.g., 
advertisements), and any other written information to be provided to subjects. The 
investigator should also provide the IRB with a copy of the Investigator Brochure, 
prescribing information, information to be provided to subjects and any updates. The 
investigator will submit documentation of the IRB approval to Sponsor or designee.  
The IRB-approved consent form must include all elements required by FDA, state, and 
local regulations, and may include appropriate additional elements. 
The investigator/designee will explain the study to each potential subject and the subject 
must indicate voluntary consent by signing and dating the approved informed consent 
form. The investigator must provide the subject with a copy of the consent form in a 
language the subject understands.  
The investigator will maintain documentation that informed consent was obtained prior to 
the initiation of any study-specific procedures. 
13.3. 
Protocol Compliance 
The IRB-approved protocol must be followed except in the case of a change that is 
intended to eliminate an immediate risk to subjects. All protocol deviations must be 
documented. 

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13.4. 
Protocol Revisions 
The Sponsor must prepare all protocol revisions. All protocol amendments must receive 
IRB approval prior to implementation. All administrative letters must be submitted to the 
IRB for their information. Copies of all correspondence with the IRB regarding this study 
must be sent to Sponsor or designee.  
New or altered consent forms required by the IRB due to a protocol change must be 
signed by all subjects for those subjects currently enrolled in the study and must be used 
for any subsequent subject enrollment. 
13.5. 
Study Monitoring 
Representatives of the Sponsor or designee must be allowed to visit study site, to review 
study records and to directly compare them with source documents (including, but not 
limited to patient and hospital records), to discuss the study conduct with the investigator 
and study staff and to verify that the investigator, study staff and facilities remain 
acceptable for the conduct of the study. Key study personnel must be available to assist 
the study monitor during these visits. 
Representatives of government regulatory authorities may also evaluate the study 
records, source documents, investigator, study staff and facilities.  
The investigator should immediately notify Sponsor or designee of any audits of this study 
by any regulatory agency, and must promptly provide copies of any audit reports. 
13.6. 
Data Collection Form Requirements 
The Sponsor will provide the site with data collection forms, be they Case Report Forms 
(CRF), either in paper format or electronic Case Report Forms (eCRF); diaries; 
questionnaires; Electronic Data Capture (EDC) screens; or other appropriate data 
collection forms as the study requires. The investigator is to provide subject data 
according to the Sponsor’s instructions, in the designated data collection form, compliant 
with GCP practices. The Sponsor will also provide the site with instructions for assisting 
other parties - such as a central laboratory - to collect data, if applicable. As instructed by 
the Sponsor, a designated central laboratory may collect data in a database and provide 
the completed database to sponsor. All data collection forms and the databases from the 
study are the exclusive property of sponsor. 
The investigator must maintain records and data during the study in compliance with all 
applicable legal and regulatory requirements. Each data point must be supported by a 
source document at the study site. Any records or documents used as the source of 
information (called the “subject source data”) are to be retained for review by authorized 
representatives of the sponsor or a regulatory agency. 

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The investigator will ensure that there is sufficient time, staff, and facilities available for 
the duration of the study to conduct and record the study as described in the protocol and 
according to all applicable guidance, laws, and regulations. 
All data collection forms (e.g., CRFs, diaries; questionnaires; EDC screens), electronic 
database entries, etc., should be completed as soon as possible after the evaluation has 
occurred. All dates appearing on the sponsor's subject data collection forms for laboratory 
tests, cultures, and other data collected, must be the dates on which the specimens were 
obtained, or the procedures performed. 
All entries into CRFs are the responsibility of the investigator and must be completed by 
the investigator or a qualified designee.  Qualified designees must be listed on the 
Delegation of Responsibilities Log with responsibility for CRF completion. The 
investigator or physician sub-investigator must electronically sign and date each subject’s 
CRF.  
13.7. 
Reports to Institutional Review Board 
The investigator should provide the IRB with reports, updates, and other information (e.g., 
safety updates, protocol amendments, and administrative letters) according to regulatory 
requirements or Institution procedures. 
13.8. 
Quality Assurance Audits 
Representatives of the Sponsor or a third party selected by the Sponsor may conduct a 
quality assurance audit of this study. During the audit, the investigator must provide the 
auditor with direct access to all relevant documents and discuss any findings with the 
auditor.  
In the event of an inspection by the FDA or other regulatory authorities, the investigator 
must give the inspector direct access to relevant documents and to discuss any findings 
with the inspector. The investigator must notify TI in the event of a FDA site audit. 
13.9. 
Records Retention 
The investigator must maintain all study records (including test article disposition, 
informed consents, CRFs/data clarification forms, source documents, correspondence, 
regulatory documents, contracts, etc.) for a period of at least five years after the study 
close-out monitoring visit. Records may be maintained in archive at the study site or 
designated off-site archive. The Sponsor will notify the investigator/Institution in writing 
when the related records are no longer needed. 
The investigator must contact the Sponsor or designee prior to destroying any records 
associated with this study.  

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If the investigator withdraws from the study the records shall be transferred to a mutually 
agreed upon designee. Written notification of such a transfer must be given to Sponsor. 
13.10. Record Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in 
a manner designed to maintain subject confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the 
written permission of the subject, except as necessary for monitoring by the Sponsor or 
designee, the FDA or other regulatory authority, or the IRB.  
The investigator and all employees and coworkers involved with this study shall not 
disclose or use for any purpose other than performance of the study, any data, records, 
or other unpublished, confidential information disclosed to those individuals for the 
purpose of the study. Prior written agreement from the Sponsor must be obtained for the 
disclosure of any said confidential information to other parties. 
14. PUBLICATION POLICY 
The data collected during this study are the property of the Sponsor.  A study site may 
not publish results of this study until after a coordinated multicenter publication has been 
submitted by the Sponsor for publication in a peer review journal. Thereafter, the study 
site may obtain written permission from the Sponsor to study data for presentation or 
publication provided that the Sponsor has the opportunity to review and comment on the 
proposed publication before it is submitted to a scientific congress or peer review journal. 
The study site agrees to provide a final draft of the publication to the Sponsor no less than 
45 days prior to submission for publication or presentation for review (including, without 
limitation, slides, abstracts, posters, manuscripts, and other publication types) that report 
any results of the study. The Sponsor shall have the right to review and comment on the 
data analysis with regard to the following concerns: 
• The accuracy of the information contained in the publication; 
• To ensure the publication is fairly balanced and in compliance with regulatory 
authorities 
• Proprietary information that is protected by the following provisions: no publication 
or manuscript shall contain any trade secret information of the sponsor or any 
proprietary or confidential information of the sponsor and shall be confined to new 
discoveries and interpretations of scientific fact. If the sponsor believes there is 
patentable subject matter contained in any publication or manuscript submitted for 
review, the Sponsor shall promptly identify such subject matter to the study site 
and study site agrees to cease publication submission until Sponsor has the 
opportunity to file a patent application covering such subject matter. 

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

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17. APPENDIX A: ELEMENTS OF INFORMED CONSENT 
a. 
Basic elements of informed consent 
In seeking informed consent, the following information shall be provided to each subject: 
1. A statement that the study involves research, an explanation of the purposes of 
the research and the expected duration of the subject's participation, a description 
of the procedures to be followed, and identification of any procedures which are 
experimental. 
2. A description of any reasonably foreseeable risks or discomforts to the subject 
3. A description of any benefits to the subject or to others which may reasonably be 
expected from the research. 
4. A disclosure of appropriate alternative procedures or courses of treatment, if any, 
that might be advantageous to the subject. 
5. A statement describing the extent, if any, to which confidentiality of records 
identifying the subject will be maintained and that notes the possibility that the 
Food and Drug Administration may inspect the records. 
6. For research involving more than minimal risk, an explanation as to whether any 
compensation and an explanation as to whether any medical treatments are 
available if injury occurs and, if so, what they consist of, or where further 
information may be obtained. 
7. An explanation of whom to contact for answers to pertinent questions about the 
research and research subject's rights, and who to contact in the event of a 
research related injury to the subject. 
8. A statement that participation is voluntary, that refusal to participate will involve no 
penalty or loss of benefits to which the subject is otherwise entitled, and that the 
subject may discontinue participation at any time without penalty or loss of benefits 
to which the subject is otherwise entitled.  
9. A 
statement 
that 
a 
description 
of 
the 
trial 
will 
be 
available 
on 
www.ClinicalTrials.gov, as required by U.S. Law. 
b. 
Additional elements of informed consent. 
When appropriate, one or more of the following elements of information shall also be 
provided to each subject: 
1. A statement that the particular treatment or procedure may involve risks to the 
subject (or to the embryo or fetus, if the subject is, or may become, pregnant) which 
are currently unforeseeable. 

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2. Anticipated circumstances under which the subject's participation may be 
terminated by the investigator without regard to the subject's consent. 
3. Any additional costs to the subject that may result from participation in the research 
4. The consequences of a subject's decision to withdraw from the research and 
procedures for orderly termination of participation by the subject. 
5. A statement that significant new findings developed during the course of the 
research which may relate to the subject's willingness to continue participation will 
be provided to the subject. 
6. The approximate number of subjects involved in the study. 
The informed consent requirements in these regulations are not intended to preempt any 
applicable Federal, State or Local laws which require additional information to be 
disclosed for informed consent to be legally effective. 
Nothing in these regulations is intended to limit the authority of a physician to provide 
emergency medical care to the extent the physician is permitted to do so under applicable 
Federal, State or Local law. 
 
DOCUMENTATION OF INFORMED CONSENT (21CFR50.27) 
Except as provided in 56.109(c), informed consent shall be documented by the use of a 
written consent form approved by the IRB and signed by the subject or the subject's 
legally authorized representative.   A copy shall be given to the person signing the form. 
Except as provided in 56.109(c), the consent form may be either of the following: 
A written consent document that embodies the elements of informed consent required by 
50.25.  This form may be read to the subject or the subject's legally authorized 
representative, but, in any event, the investigator shall give either the subject or the 
representative adequate opportunity to read it before it is signed. 
A short form written consent document stating that the elements of informed consent 
required by 50.25 have been presented orally to the subject or the subject's legally 
authorized representative.  When this method is used, there shall be a witness to the oral 
presentation.  Also, the IRB shall approve a written summary of what is to be said to the 
subject or the representative.  Only the short form itself is to be signed by the subject or 
the representative.  However, the witness shall sign both the short form and a copy of the 
summary, and the person actually obtaining the consent shall sign a copy of the summary.  
A copy of the summary shall be given to the subject or the representative in addition to a 
copy of the short form. 

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Table 2 Static Physician’s Global Assessment Score (averaged over all lesions) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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(
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 

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PGWBI © 1984 Harold J. Dupuy, All rights reserved