A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase IIb Clinical Trial (PLANTCOAT-IIb) to Evaluate the Efficacy and Safety of a Botanical Total Coumarin (TC) Cream in Treating Patients With Psoriasis Vulgaris
Phase: PHASE2
Conditions: Psoriasis Vulgaris, Topical Administration
Sponsor: Psoriasis Research Institute of Guangzhou

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Protocol for Phase IIb Clinical Trials of 
Total Coumarin Cream 
A 
PHASE 
2B, 
MULTI-CENTER, 
DOUBLE-BLIND, 
RANDOMIZED, 
PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND 
SAFETY OF TOTAL COUMARIN CREAM IN TREATING PATIENTS WITH 
PSORIASIS VULGARIS 
 
Protocol Number: 105883-1 
 
Product Name: Total coumarin cream (蛇床子总香豆素软膏®) 
 
Other name: TC Cream 
 
Phase: phase IIb 
 
 
Sponsored by: Psoriasis Research Institute of Guangzhou (PRIG), China 
 
  
 
 
Version Number: 00 
 
Original date: Jan. 29th, 2015 
 
Confidentiality Statement 
This document is confidential and is to be distributed for review only to investigators, 
potential investigators, consultants, study staff, and applicable independent ethics 
committees or institutional review boards. The contents of this document shall not be 
disclosed to others without written authorization from PRIG, unless it is necessary to 
obtain informed consent from potential study participants. 

Protocol Version：00 
 
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STATEMENT OF COMPLIANCE 
This research will be carried out in accordance with Good Clinical Practice (GCP) as set 
out by the International Conference on Harmonization (ICH), the basic principles defined 
in the U.S. Code of Federal Regulations (21 CFR Part 312), and the principles enunciated 
in the World Medical Association Declaration of Helsinki (Edinburgh, Scotland, 2000). 
The Investigational New Drug (IND) for the study has been reviewed by the FDA. 
 

Protocol Version：00 
 
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Table of Contents 
PROTOCOL SYNOPSIS ......................................................................................................................... 1 
Schematic Flow of Study Design ............................................................................................................. 4 
1. INTRODUCTION ................................................................................................................................ 5 
1.1 Background ................................................................................................................................. 5 
1.1.1 Study Disease: Psoriasis Vulgaris ........................................................................................ 5 
1.1.2 Study Agent: TC Cream ....................................................................................................... 6 
1.2 Rationale ..................................................................................................................................... 6 
1.3 Control Agent: Placebo ............................................................................................................... 6 
1.4 Route of Administration ............................................................................................................. 6 
1.5 
Summary of Previous Pre-clinical Studies ........................................................................... 6 
1.5.1 Pharmacology ...................................................................................................................... 6 
1.5.2 Toxicology ........................................................................................................................... 7 
2. OBJECTIVES ....................................................................................................................................... 7 
3. STUDY DESIGNS ............................................................................................................................... 7 
3.1 Randomization ............................................................................................................................ 8 
3.2 Blinding ...................................................................................................................................... 8 
3.3 Patient Selection ......................................................................................................................... 8 
3.3.1 Study Population .................................................................................................................. 8 
3.3.2 Sample Size ......................................................................................................................... 8 
3.3.3 Screening Procedures .......................................................................................................... 8 
3.3.4 Inclusion Criteria ................................................................................................................. 8 
3.3.5 Exclusion Criteria ................................................................................................................ 9 
3.3.6 Washout Period .................................................................................................................... 9 
3.4 Treatment Plan .......................................................................................................................... 10 
3.4.1 Administration ................................................................................................................... 10 
3.4.2 Duration of Therapy .......................................................................................................... 10 
3.4.3 Treatment Compliance ....................................................................................................... 10 
3.4.4 Concomitant Drug Treatment ............................................................................................ 10 
3.4.5 Early Withdrawal of Subjects ............................................................................................ 10 
3.5 Agent Formulation and Procurement ....................................................................................... 11 
3.5.1 Agents Accountability ....................................................................................................... 11 
3.5.2 Study Agents Supply ......................................................................................................... 11 
3.5.3 Storage Conditions ............................................................................................................ 11 
3.5.4 Stability .............................................................................................................................. 12 
4. STUDY PROCEDURES AND SCHEDULE OF EVENTS .............................................................. 13 
4.1 Schedule of Events ................................................................................................................... 13 
4.2 Observations of Curative Effects .............................................................................................. 14 
4.3 Scoring of Clinical Symptoms .................................................................................................. 14 
4.3.1 Severity of local signs - Phenotypes .................................................................................. 14 
4.3.2 Extent - Body Surface Area (BSA) Affected ..................................................................... 15 
4.3.3 Symptoms - Pruritus (ITChing) ......................................................................................... 16 
5. MEASUREMENT OF EFFECT ........................................................................................................ 17 

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5.1 
Clinical End Points ............................................................................................................. 17 
5.1.1 Investigator’s Static Global Assessment（ISGA）Scale Definition ............................. 17 
5.1.2 Target Lesion .................................................................................................................. 18 
5.1.3 Psoriasis Area and Severity Index (PASI) ......................................................................... 19 
5.1.4 Psoriasis Disability Index（PDI） ................................................................................. 20 
5.1.5 Dermatology Life Quality Index (DLQI) ....................................................................... 20 
5.2 
Guidelines for Evaluation of Measurable Disease ............................................................. 21 
6. SAFETY ............................................................................................................................................. 21 
6.1 
Expected Adverse Events ................................................................................................... 21 
6.2 
Adverse Event Definition and Classification ..................................................................... 21 
6.3 
Serious Adverse Event ........................................................................................................ 22 
6.4 
Laboratory and Other Safety Assessment Abnormalities Reported as AEs and SAEs ...... 22 
6.5 
Pregnancy ........................................................................................................................... 22 
6.6 
Severity of Adverse Events ................................................................................................ 22 
6.7 
Relationship to Study Drug ................................................................................................ 23 
6.8 
Procedures for Collecting Adverse Event Information ...................................................... 23 
6.9 
Procedures for Reporting Adverse Events .......................................................................... 23 
7. DROPOUT, WITHDRAWAL AND TERMINATION ..................................................................... 24 
8. DATAMANAGEMENT ..................................................................................................................... 24 
8.1   Fill in CRF ........................................................................................................................... 24 
8.2 
Data Entry and Amendment ............................................................................................... 25 
8.3 
Data Management Responsibilities .................................................................................... 25 
9. DATA ANALYSIS AND STATISTICAL CONSIDERATIONS ........................................................ 25 
9.1 
Sample Size Assumptions ................................................................................................... 25 
9.2 
Data Analysis Considerations ............................................................................................. 26 
9.2.1 Efficacy Analysis Populations ........................................................................................ 26 
9.2.2 Safety Analysis Populations ........................................................................................... 26 
9.2.3 Analysis Data Sets .......................................................................................................... 26 
9.2.4 Analysis Plan .................................................................................................................. 26 
10. ETHICAL AND REGULATORY REQUIREMENTS ................................................................... 27 
10.1 Investigator Responsibilities ................................................................................................... 27 
10.2 Ethical Review ........................................................................................................................ 27 
10.3 Informed Consent ................................................................................................................... 27 
10.4 Confidentiality ........................................................................................................................ 27 
10.5 Amendments and Protocol Revisions ..................................................................................... 27 
10.6 Study Termination .................................................................................................................. 28 
11. MONITORING OF THE STUDY ................................................................................................... 28 
11.1 On-Site Audits/Inspections ..................................................................................................... 28 
11.2 Monitoring .............................................................................................................................. 28 
12. ARCHIVES/RECORD RETENTION ............................................................................................. 28 
13. REFERENCES ................................................................................................................................. 29 
 
 

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List of Abbreviations 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
CIB 
Clinical Investigator’s Brochure 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent or Institutional Ethics Committee 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
MOP 
Manual of Procedures 
NDA 
New Drug Application 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
WHO 
World Health Organization 

Protocol Version: 00 
 
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PROTOCOL SYNOPSIS 
Full Title 
A Double-Blind, Randomized, Placebo-Controlled, Multi-Center Phase Ⅱb Clinical 
Trial to Evaluate the Efficacy and Safety of TC Cream in Treating Patients with 
Psoriasis Vulgaris  
Short Title 
Phase Ⅱb Efficacy and Safety Evaluation of TC Cream in Treating Patients with 
Psoriasis Vulgaris. 
Protocol 
Number 
105883-1 
Clinical 
Trial 
Phase 
Phase Ⅱb 
IND Sponsor 
Psoriasis Research Institute of Guangzhou, Guangdong, China 
Study Centers 
Multi-centers: (1)  (2) 
Primary 
Objective 
To observe the efficacy and safety of TC Cream twice daily compared to placebo over 
8 weeks in subjects of US population with stable psoriasis.  
Secondary 
Objectives 
To evaluate the effects and improvements of TC Cream on the quality of life in 
subjects with psoriasis vulgaris (stable stage) based on Psoriasis Disability Index 
(PDI) and Dermatology Life Quality Index (DLQI); and to determine whether there is 
further improvement or recurrence of psoriasis after the cessation of TC Cream after 8 
weeks treatment of psoriasis vulgaris of stable stage.  
Exploratory 
Objectives 
To investigate and summarize the curative effects and recurrence rate of TC Cream on 
treated psoriasis patients of US population  
Sample Size 
Total: 88 Subjects (44 for the treatment group and 44 for the control group) 
Clinical 
centers 
Stable Stage 
Total 
Arm 1 
TC 
Arm 2 
Vehicle 
Center 1 
 
 
 
Center 2 
 
 
 
Total 
 
 
 
 
Study 
Population 
Male or female patients of 18-70 years old of any race with psoriasis vulgaris of stable 
stage 
Duration 
of 
Administration 
8 weeks  
Washout 
4 weeks for any topical or systemic corticosteroids, anti-inflammatories, antibiotics, 
3-months for any systemic retinoids or biologics, or any investigational treatment 

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period 
Duration 
of 
Study 
6 months 
Study Design 
Multi-center, randomized, double blind (Subject, Investigator), placebo controlled, 
parallel assignment 
Study 
Agent 
/Intervention 
Description 
Treatment group:  
TC Cream: 0.3g/cm2, applied to afflicted area after cleaning the skin with warm water; 
twice daily (morning and evening); dosage should not exceed 25g/day 
Control group (placebo):  
Vehicle of TC Cream: 0.3g/cm2, applied to afflicted area after cleaning the skin with 
warm water; twice daily (morning and evening); dosage should not exceed 25g/day 
Concomitant 
Medications/ 
Therapies 
None 
Safety 
Considerations 
and 
Monitoring of 
adverse events 
Do not expect any side effect other than mild red pigmentation which will disappear 
after the drug withdrawal. 
Diagnosis and 
Main Inclusion 
Criteria 
ü Male or female of 18-70 years old 
ü  Women of childbearing age must be using birth control strategies defined by 
one of the following: 1) a barrier method (condom) and 2) oral contraceptives, 
during the 8-weeks study period. 
ü Consistent with diagnostic criteria of psoriasis vulgaris  
ü ISGA score ≥ 2 (at least mild severity) 
ü BSA (stable stage group): 1% ≤ to ≤20%  
Note: Randomized, male-female ratio should be properly taken into consideration.  
Main 
Exclusion 
Criteria 
ü Subjects in pregnancy, preparing for pregnancy or breast feeding 
ü History of hyperergic or photosensitivity 
ü History of complicated cardiovascular disease, cerebrovascular disease, 
severe primary diseases in hepatic, kidney and hematopoietic system, or 
patients who are diagnosed with psychotic disorders 
ü Within 2/4 weeks prior to randomization the patients have taken treatment 
with following approved or investigational psoriasis therapy of the target 
lesions:  
o 
Topical treatments 
o 
PUVA, UVB or Grenz ray therapy 
o 
Any systemic treatments other than biologicals with a possible effect 
on psoriasis (e.g., corticosteroids, vitamin D analogues, retinoids, 
hydroxycarbamide, azathioprine, methotrexate, cyclosporine, other 
immunosuppressants). 

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o 
Any types of investigational therapy for psoriasis within the last 30 
days 
ü Within 3 months prior to randomization the patients have taken systemic 
treatment with retinoids or biological therapies (marketed or others) with a 
possible effect on psoriasis (e.g., alefacept, efalizumab, etanercept, 
infliximab). 
ü Planned initiation of, or changes to, concomitant medication that could affect 
psoriasis (e.g., beta blockers, anti-malaria drugs, lithium) during the 
double-blind phase of the study. 
Endpoints 
 
Observation of Curative Effects: 
(1) Severity of local signs - Phenotypes  
a. 
Induration (average over all lesions) 
b. Erythema (average over all lesions) 
c. 
Scaling (average over all lesions) 
  （2）Extent - Body Surface Area (BSA) affected 
  （3）Symptoms - Pruritus/itching (average over 24 hours) 
  （4）Visual assessment: Digital photographs on the target skin lesion 
Note: (1) All patients will be examined and photographed before (first visit) and after 
(end of the curative treatment) treatment with TC Cream or placebo. 
(2) The investigator(s) can, not must, consider enrolling the patients may have a lesion 
on elbow and/or knee. However, the patients who have no lesion on elbow or knee or 
only have a lesion on one of parts can be enrolled into this research. 
Outcome Measures: 
• 
Primary Endpoint: 
(1) Investigator's Static Global Assessment (ISGA)  
(2) Assessment of Targeted Lesions 
• 
Secondary Endpoint: 
(1) PASI ≥ 75% improvement 
• 
Tertiary Endpoint:   
(1) Psoriasis Disability Index (PDI) 
(2) Dermatology Life Quality Index (DLQI) 
 
Statistical Analysis: 
Comparison between two groups will be made using the t-test with two-sided 95% 
confidence interval (CI) for the difference in response rates between the two treatment 
groups (ITT, TC vs. Vehicle). A P-value< 0.05 is considered to be statistically 
significant. 
Frequency of Evaluation:  
- 
0 (before treatments), 2, 4, 6 and 8 weeks 
- 
After the initial 8 weeks of treatment, there will be a follow up period of 4 
weeks during which no treatment is used. 

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Schematic Flow of Study Design 
 
 
 
 

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1. INTRODUCTION 
1.1 Background 
1.1.1 Study Disease: Psoriasis Vulgaris 
Psoriasis is a common, genetically determined, inflammatory, and proliferative skin 
disease. It is a disabling disease and may even be life-threatening on rare occasions. The 
duration may vary from a few weeks to a whole lifetime. The clinical course is 
unpredictable, but in most patients, psoriasis is a chronically remitting and relapsing 
disease. It has significant social, psychological, and economic consequences. The impact 
of psoriasis on the quality of life is reported to be comparable with that observed in other 
chronic medical conditions such as diabetes and depression. Epidemiological studies 
indicate that psoriasis is associated with other serious conditions such as diabetes, heart 
disease, and obesity. According to the National Institutes of Health, as many as 7.5 million 
Americans have psoriasis. Chronic psoriasis vulgaris is the most common form of 
psoriasis and affects about 90% of patients with psoriasis [1].  
 
Although there is currently no cure for psoriasis, there are three categories of treatment 
options (Topical, Phototherapy, and Systemic) [2] that can clear psoriasis for a period, yet 
each treatment has advantages and disadvantages. Ultraviolet light treatment is frequently 
combined with topical (e.g., coal tar, calcipotriol) or systemic (e.g., retinoids) treatment. 
Long-term toxicities are observed with all currently available systemic treatments[3,4], 
such as teratogenic effects and the influence on lipid metabolism with retinoids, 
cumulative liver toxicity and the risk of bone marrow suppression and of malignancies 
with methotrexate, hypertension, renal dysfunction, and risk of malignancies with 
cyclosporine A, and increased risk of squamous-cell carcinoma and melanoma with PUVA 
therapy. A few new biologics have been developed to treat psoriasis; however, not only 
are the drug prices extremely high, but they are also often associated with severe adverse 
effects.  
 
Due to the high frequency of adverse reactions to systemic and Phototherapy, topical 
agents are often used as first-line therapy for plaque psoriasis. These include salicylic acid, 
steroids, Vitamin D analogues (such as calcipotriol), tazarotene, dithranol, coal tar 
extracts, and a combination of any of these agents. Retinoid drugs cause a high rate of 
irritant reactions on the skin, and as a result, they can only be used in the stable stage of 
psoriasis; while hormone and immunosuppressive treatments have evident side effects, 
their short-term efficacy is reasonably good. Recurrence is common after withdrawal of 
these treatments, and the disease tends to turn into chronic, stubborn, and become more 
challenging to treat. 

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1.1.2 Study Agent: TC Cream 
TC Cream is a botanical drug developed for the topical treatment of psoriasis vulgaris. It 
has been proven through phase II and phase III clinical trials conducted in China to have 
remarkable efficacy and minimal side effects, not only for patients with stable disease but 
also during flare. It is especially effective for first-time psoriasis patients who have never 
used any other treatment in the past. 
 
The TC Cream drug product contains a well-characterized plant extract, TC, from a 
Chinese traditional herb, and a partially purified crystalline powder. It can be used for 
various skin illnesses. The activity is considered to arise from the whole mixture of the 
extract, not from an individual component. Drug substance and drug product 
specifications have two ID tests, including an HPLC method, to achieve effective 
treatments. So far, the three-month accelerated stability data and long-term (36 months for 
the drug substance and 45 months for the TC Cream) storage at room temperature have 
not shown any negative trends. Robust manufacturing of the drug substance and the drug 
product has been established with tight specifications to assure consistent quality control 
of the drug product. 
1.2 Rationale 
TC Cream has been shown to accelerate cutin reduction, reduce inflammation, prevent 
anaphylaxis and allergy, and exhibit notable antibacterial and anti-pruritic effects through 
pre-clinical studies and Phase III and Phase II safety and efficacy clinical studies in China. 
In addition, it can improve the pathological changes of over-proliferation and 
parakeratosis of epidermal cells in psoriasis. 
 
1.3 Control Agent: Placebo 
Vehicle of TC Cream with the same manufacturing formulation and process, without the 
drug substance added. 
 
1.4 Route of Administration 
The study agents are for external/topical use only. Apply a thin layer (0.3g/cm2) of TC 
Cream to the affected area(s) twice daily. Daily doses exceeding 50g have not been 
systematically studied. 
 
1.5 Summary of Previous Pre-clinical Studies 
1.5.1 Pharmacology  
Pharmacological experiments show that TC Cream can inhibit mitosis in the vaginal 
epithelial cells of mice; it can increase the thickness of the granular layer in the skin 
scales of rat tails; it has a markedly strong inhibition of passive cutaneous anaphylaxis in 

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rats. In addition, it significantly inhibits croton oil-induced mouse ear swelling and 
albumin-induced rat paw edema and evidently raises the itch threshold to histamine 
phosphate in guinea pigs. Research shows that TC Cream promotes cutin reduction, 
anti-inflammation, anti-anaphylaxis, and anti-allergy effects, as well as notable 
antibacterial and antipruritic effects. Besides, it can improve the pathological changes of 
over-proliferation and parakeratosis of epidermal cells in psoriasis. It is an effective 
psoriasis treatment. 
1.5.2 Toxicology 
• 
The LD50 for intragastric administration in acute toxicity tests in mice is 409.85 
mg/kg in females and 463.90 mg/kg in males. 
• 
No abnormality was observed in rat long-term (90 days) toxicity tests (by intragastric 
administration).  
• 
TC Cream, through dermal irritation tests on the local skin of guinea pigs, indicates: 
no erythema, edema, ulceration, or other irritant reactions on the local skin. 
• 
The anaphylaxis test on guinea pigs: no abnormal effects observed. 
• 
In acute toxicity tests, different concentrations of the TC Cream were applied to the 
entire skin and to skin lesions on rabbits, and no abnormalities were observed. 
• 
In long-term toxicity tests on rabbits and rats, TC Cream was applied continuously to 
the entire skin and to skin lesions for 90 days, without any toxic reactions or animal 
deaths. 
• 
There are no side effects found in the liver, kidney, cardiovascular, or other systems, 
with the local use of TC Cream 
 
2. OBJECTIVES 
• To observe the efficacy and safety of TC Cream twice daily compared to placebo 
over 8 weeks in subjects of the US population of patients with psoriasis vulgaris 
(stable stage) based on Investigator’s Static Global Assessment (ISGA), Target 
Lesion, Psoriasis Area and Severity Index (PASI). 
• To evaluate the effects and improvements of TC Cream on the quality of life in 
subjects with psoriasis vulgaris based on Psoriasis Disability Index (PDI) and 
Dermatology Life Quality Index (DLQI), and to determine whether there is further 
improvement or recurrence of psoriasis after the cessation of TC Cream after 8 
weeks of treatment for psoriasis.  
• To investigate and summarize the curative effect and recurrence rate of TC Cream 
on treated psoriasis patients of the US population. 
 
3. STUDY DESIGNS 
This is a double-blind, randomized, placebo-controlled, parallel-controlled, multi-center, 
phase IIb clinical trial. 
This phase Ⅱb clinical trial includes two study groups: a treatment group and a placebo 

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group, and it will be conducted at multiple centers. The total number of sample cases 
needed for this trial is 88 patients enrolled. The subjects are both inpatients and 
outpatients with BSA ≥1% to ≤20%. Approximate time to complete study enrollment is 
1～2 days. The expected duration of subject participation is 8 weeks. After the initial 8 
weeks of treatment, there will be a 4-week follow-up period during which no treatment is 
used. 
 
3.1 Randomization 
Subjects will be randomly assigned to a treatment agent according to a predetermined 
computer-generated randomization scheme. 
 
Subjects will be assigned consecutive subject numbers in ascending order. This number 
will identify the subject and determine the treatment of drug product administration 
according to the randomization scheme. 
 
3.2 Blinding 
Double blinding: the subject(s), investigator(s), monitor, and, in some cases, data 
analyst(s) will be blinded from the treatment agents throughout the study. 
 
3.3 Patient Selection 
3.3.1 Study Population 
The study will include psoriasis patients in the US population.  
3.3.2 Sample Size 
A total of 88 subjects in the study centers will be included. 
3.3.3 Screening Procedures 
Screening procedures will include the following: 
• medical history 
• vital signs (blood pressure, pulse rate, respiration, and temperature) 
• demographic data collection and measurements of height and weight 
• photocopies of the affected skin 
• physical examination. 
3.3.4 Inclusion Criteria 
• 
Age of 18-70 years old. Both men and women, and members of all races and ethnic 
groups, will be included 
• 
Consistent with the diagnostic criteria of stable-stage psoriasis vulgaris, and have at 
least two target lesions suitable for evaluation  

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• 
Women of childbearing age must be using birth control strategies defined by one of 
the following: 1) a barrier method (condom) and 2) oral contraceptives, during the 
8-week study period. 
• 
ISGA score ≥ 2 (at least mild severity) 
• 
BSA (stable stage group): 1%≤ to ≤20% 
• 
Signed a written informed consent document 
• 
No additional exposure to the sun 
Note: Randomized, male-female ratio should be adequately taken into consideration. 
3.3.5 Exclusion Criteria 
• 
Subjects in pregnancy, preparing for pregnancy, or breastfeeding 
• 
History of hyperergic or photosensitivity 
• 
History of complicated cardiovascular disease, cerebrovascular disease, severe 
primary diseases of hepatic, renal, and hematopoietic systems, or patients who are 
diagnosed with psychotic disorders 
• 
History of photosensitive diseases such as porphyria, chronic actinic dermatitis, 
Xeroderma 
• 
Within 2/4 weeks before randomization, the patients have taken treatments with the 
following approved or investigational psoriasis therapy of the target lesions:  
o Topical treatments 
o PUVA, UVB, or Grenz ray therapy. 
o Any systemic treatments other than biologicals with a possible effect on 
psoriasis 
(e.g., 
corticosteroids, 
vitamin 
D 
analogues, 
retinoids, 
hydroxycarbamide, 
azathioprine, 
methotrexate, 
cyclosporine, 
other 
immunosuppressants). 
o Any other type of investigational therapy for psoriasis  
• 
Within 3 months before randomization, patients have received systemic retinoid or 
biological therapy (marketed or otherwise) that may affect psoriasis (e.g., alefacept, 
efalizumab, etanercept, infliximab). 
• 
Planned initiation of, or changes to, concomitant medication that could affect 
psoriasis (e.g., beta blockers, anti-malaria drugs, lithium) during the double-blind phase of 
the study.  
• 
The history of allergic reactions attributed to similar dermatological drugs are 
excluded according to specific cases decided by investigators 
3.3.6 Washout Period  
• 
4-weeks for any topical or systemic corticosteroids, anti-inflammatories, antibiotics, 
• 
3-months for any systemic retinoids or biologics, or any investigational treatment 
• 
Only specific procedures are performed as indicated in the table of Schedules of 

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Events, if subjects need washout periods 
 
3.4 Treatment Plan 
3.4.1 Administration 
3.4.1.1 Treatment group: 
TC Cream: 0.3g/cm2, applied to the afflicted area after cleaning the skin with warm water; 
twice daily (morning and evening); dosage should not exceed 25g/day. 
 
3.4.1.2 Control group (placebo): 
Vehicle of TC Cream: 0.3g/cm2, applied to the afflicted area after cleaning the skin with 
warm water; twice daily (morning and evening); dosage should not exceed 25g/day. 
3.4.2 Duration of Therapy 
Subjects should continuously apply the study agent twice daily (morning and evening) for 
8 weeks. 4 weeks after treatment is completed, patients are required to return for study 
follow-up. 
3.4.3 Treatment Compliance 
The participants will be instructed to return all unused or part-used medication and 
packaging from used medication at each visit. The Investigator may withdraw participants 
if they consider compliance unsatisfactory. 
3.4.4 Concomitant Drug Treatment 
The subjects can use emollients (non-medicated moisturizers) during the study, but not on 
the day of the visit. 
 
Subjects enrolled in this study will not be taking concomitant medications for other 
diseases. 
 
If drug therapy for other diseases is required during the study, the investigator/study 
director will decide whether to continue or discontinue the subject’s participation, and any 
corresponding medications should be recorded. 
3.4.5 Early Withdrawal of Subjects 
In the absence of treatment delays due to adverse events, treatment may continue until one 
of the following criteria applies: 
• 
Voluntary patient withdrawal 
• 
The investigator’s decision that it is in the patient’s best interest to withdraw 
• 
If the patient becomes pregnant 

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• 
Noncompliance 
• 
Significant protocol violation 
• 
Safety reasons if any of the following occur: 
o Disease progression 
o Intercurrent illness that prevents further administration of treatment 
o Unacceptable adverse events(s) 
o Patient decides to withdraw from the study, or 
o General or specific changes in the patient's condition render the patient 
unacceptable for further treatment in the investigator's judgment. 
• 
For any reason, at the Sponsor’s or Investigators’ discretion  
 
3.5 Agent Formulation and Procurement 
3.5.1 Agents Accountability 
The Investigator, or a responsible party designated by the Investigator, must maintain a 
careful record of the inventory and disposition of the study agent. 
 
At the completion of the study, all unused study drug(s) will be returned to the sponsor 
unless authorized by the sponsor for appropriate disposal. 
 
3.5.2 Study Agents Supply 
The sponsor (PRIG) will supply sufficient quantities of the study drugs to allow 
completion of this study. Study agents (test and control) are supplied in identical 25g 
collapsible tubes. 
 
Designated clinical staff will be responsible for monitoring the receipt, storage, 
dispensing, and accounting for all study medications in accordance with Good Clinical 
Practice (GCP) and FDA regulations. 
 
The appearance and packaging of the placebo will be consistent with those of the 
investigational product. The subjects and the investigators couldn’t distinguish them. The 
product name, strength, the manufacturer’s name, and lot/batch number will be identified 
on each container. The control agent will also include an expiry date. The study drugs will 
be placed under appropriate storage conditions in an area with controlled access.  
 
Every subject will receive a packaging kit; exterior and interior packages should be kept 
with their respective labels. 
 
3.5.3 Storage Conditions 
Store at room temperature 15º C - 25º C (59º F - 77º F). Do not freeze. Keep tightly closed 
and away from light. Keep out of reach of children. 

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3.5.4 Stability 
The study agent (both drug substance and finished product) is stable for at least 36 months 
at room temperature in shaded places

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4. STUDY PROCEDURES AND SCHEDULE OF EVENTS 
4.1 Schedule of Events 
Study stages 
Pre- 
Study 
Treatment Study 
Off 
Study  
Time point 
-1 
0 
1 
2 
3 
4 
5 
Visit time 
Scr. 
Wk 0 
Wk 2 
Wk 4 
Wk 6 
Wk 8 
Wk 12 
Informed consent 
× 
※ 
 
 
 
 
 
Demographics 
× 
※ 
 
 
 
 
 
Medical history 
× 
※ 
 
 
 
 
 
Physical exam 
(Blood Pressure, Pulse Rate, 
Respiration 
Rate, 
and 
Temperature) 
× 
× 
× 
× 
× 
× 
× 
Pregnancy test 
× 
※ 
 
× 
 
× 
 
Psoriasis Evaluation 
× 
×……………………………………………× 
× 
Body Surface Area (BSA) 
× 
× 
× 
× 
× 
× 
× 
Erythema (Redness) 
× 
× 
× 
× 
× 
× 
× 
Induration (Thickness) 
× 
× 
× 
× 
× 
× 
× 
Desquamation (scaling) 
× 
× 
× 
× 
× 
× 
× 
Pruritus (itching) 
× 
× 
× 
× 
× 
× 
× 
Autochrome plate shot at 
the target skin lesion: (1) 
articulation 
of 
elbow/knee;(2) trunk 
 
× 
 
 
 
× 
 
Safety Evaluation 
 
×……………………………………………× 
 
Blood convention  
(HB, WBC, RBC, PLT) 
 
× 
 
 
 
× 
 
Comprehensive 
Chemistry 
Panel & Complete Blood 
Count (CBC)  
 
× 
 
 
 
× 
 
Blood coagulation test 
 (PT, PPT) 
 
× 
 
 
 
× 
 
Urine convention  
(Protein, RBC, WBC) 
 
× 
 
 
 
× 
 
Liver and renal functions  
(ALT, BUN, Cr) 
 
× 
 
 
 
× 
 
ECG  
 
× 
 
 
 
× 
 
Adverse event evaluation 
 
×……………………………………………× 
 

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Note: Pre-study -1 and week 0 are combined if washout period is not needed; ※ indicated the 
procedure is not needed if pre-study -1 and week 0 are separate 
Off-study evaluation: evaluations of the conditions of patients’ affected skin after 4 weeks of 
the study have to be documented in case of any potential disease rebounds. 
 
4.2 Observations of Curative Effects 
The following symptoms should be observed and documented for evaluation: 
(1) Severity of local signs - Phenotypes 
a. Induration (average over all lesions) 
b. Erythema (average over all lesions) 
c. Scaling (average over all lesions) 
(2) Extent - Body Surface Area (BSA) affected 
(3) Symptoms - Pruritus/itching (average over 24 hours) 
(4) Visual assessment: Digital photographs on the target skin lesion: (1) articulation of 
elbow/knee (2) trunk (major & target affected area) 
 
Note: (1) All patients will be examined and photographed before (first visit) and after 
(end of the curative treatment) treatment with TC Cream or placebo.  
 (2) The investigator(s) can, not must, consider enrolling patients who may have a 
lesion on the elbow and/or knee. However, patients with no lesion in the elbow or knee, or 
only a lesion in one of these areas, can be enrolled in this research. 
 
4.3 Scoring of Clinical Symptoms 
4.3.1 Severity of local signs - Phenotypes 
a) Induration (elevation) 
The NPF induration card is to be used to assist the induration assessments. 
Table 1 Induration (average over all lesions) 
Score 
Description  
Definition (induration, edema, or elevation) 
0 
Clear  
plaque induration = 0 mm 
1 
Almost Clear 
plaque induration = 0.25 mm 
2 
Mild 
plaque induration = 0.5 mm 
3 
Moderate  
plaque induration = 0.75 mm 
4 
Severe 
plaque induration = 1.0 mm 
5 
Very Severe 
plaque induration ≥ 1.25 mm 
b) Erythema (Redness) 
Table 2 Erythema (average over all lesions) 
Score 
Description 
Definition 
0 
Clear 
No evidence of erythema  (hyperpigmentation may be present)  
1 
Almost Clear 
light or pale discrete coloration 
2 
Mild 
pinkish red coloration 

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15 
 
3 
Moderate 
reddish patchy coloration 
4 
Severe  
bright red coloration 
5 
Very severe 
dusky to deep red coloration 
 
c) Scaling  
Table 3 Scaling (average over all lesions) 
Score 
Description 
Definition (Scaling, vesiculation) 
0 
Clear 
no evidence of scaling 
1 
Almost Clear 
fine, barely visible scaling (≤5%) 
2 
Mild  
thin, fine scaling 
3 
Moderate 
mainly crusted scaling 
4 
Severe 
non-adhesive , thick, crusted scaling 
5 
Very Severe 
extensive, very thick, adhesive/tenacious scale predominates 
 
4.3.2 Extent - Body Surface Area (BSA) Affected 
A transparent plastic Square Ruler of 9cm x 9cm (see figure 1) is to be used to measure 
the BSA. 
Table 4 Body Surface Area (BSA)  
Score 
Proposed Degree to cover the phase 2b 
clinical design (≤20%) 
Comparison 
to 
PASI Area Scale 
0 
<1% 
0 
1 
1-5% 
1~9% 
2 
6-10% 
 
3 
11-15% 
10-29% 
4 
16-20% 
 
5* 
21-30% 
 
6* 
31-40% 
30-49% 
7* 
41-60% 
50-69% 
8* 
61-80% 
70-89% 
9* 
81-100% 
90-100% 
*Will not be used for the proposed phase II trials, since the inclusion criteria is BSA ≤20%. 

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Figure 1 Square Ruler of 9cm x 9cm 
1 
2 
3 
4 
5 
6 
7 
8 
9 
2 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
 
6 
 
 
 
 
 
 
 
 
7 
 
 
 
 
 
 
 
 
8 
 
 
 
 
 
 
 
 
9 
 
 
 
 
 
 
 
 
4.3.3 Symptoms - Pruritus (Itching)   
Table 5 Patient Assessment of Itching/Pruritis 
Score 
Description 
Definition (itching/pruritis) 
defined score = average over 24 hours 
0 
Clear 
No itching 
1 
Almost Clear 
Occasional (episodic) and localized itching without disturbance of 
normal work, school and sleep. 
2 
Mild 
Some mild itching, annoyance to daily life without sleep disturbance 
3 
Moderate 
Generalized irregular itching with somewhat disturbance in sleep 
4 
Severe 
Generalized and continuous itching; frequent sleep disturbance. 
5 
Very severe 
Generalized and continuous itching with sleep disturbance; distressing; 
extensively interfere with daily activities. 

Protocol Version: 00 
 
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5. MEASUREMENT OF EFFECT 
5.1 Clinical End Points 
Clinical outcomes will be evaluated by following the criteria: 
1. Primary Endpoint: 
 
(1) Investigator's Static Global Assessment (ISGA) 
(2) Assessment of Target Lesions 
2. Secondary Endpoint: 
(1) PASI≥ 75% improvement  
3. Tertiary Endpoint: 
(1) Psoriasis Disability Index (PDI)  
(2) Dermatology Life Quality Index (DLQI). 
 
For the purposes of this study, patients should be evaluated at baseline (0) and reevaluated 
for response at 2, 4, 6, and 8 weeks. In addition, a rebound evaluation should also be 
obtained 4 weeks after the final evaluation of week 8. 
 
The efficacy evaluation of all outcomes will be static ordinal, integer-valued, and scaled 
(e.g., success or failure), where 'success' involves a score of Clear/Almost Clear and a 
2-grade improvement.  
5.1.1 Investigator’s Static Global Assessment（ISGA）Scale Definition 
Table 6 Investigator's Static Global Assessment (ISGA) Scale Definition 
Score 
Grade 
Definition 
0 
None 
No plaque elevation above normal skin level; may have residual 
non-erythematous discoloration; no psoriatic scale; no itching. 
Plaque elevation = 0 (no elevation over normal skin) 
Scaling = 0 (no scale) 
Erythema = ± (hyperpigmentation, pigmented macules, diffuse faint pink or red 
coloration) 
1 
Minimal 
Essentially flat with possible trace elevation; faint erythema; no psoriatic scale 
Plaque elevation = ± (possible but difficult to ascertain whether there is a slight 
elevation above normal skin) 
Scaling = ± (surface dryness with some white coloration) 
Erythema = up to moderate (up to definite red coloration) 
Majority of lesions have individual scores for induration, erythema, scaling, 
BSA and Pruritus (as described above) that average 1. 
2 
Mild 
Slight plaque elevation, scaling, and/or erythema. 
Plaque elevation = slight (slight but definite elevation, typically edges are 
indistinct or sloped) 
Scaling = fine (fine scale partially or mostly covering lesions) 
Erythema = up to moderate (up to definite red coloration) 
Majority of lesions have individual scores for induration, erythema, scaling, 

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BSA and Pruritus (as described above) that average 2. 
3 
Moderate 
Moderate plaque elevation, scaling, and/or erythema. 
Plaque elevation = moderate (moderate elevation with rough or sloped edges) 
Scaling = coarser (coarse scale covering most of all of the lesions) 
Erythema = moderate (definite red coloration) 
Majority of lesions have individual scores for induration, erythema, scaling, 
BSA and Pruritus (as described above) that average 3. 
4 
Severe 
Marked plaque elevation, scaling, and/or erythema.  
Plaque elevation = marked (marked elevation typically with hard or sharp 
edges) 
Scaling = coarse (coarse, non-tenacious scale predominates covering most or all 
of the lesions) 
Erythema = severe (very bright red coloration) 
Majority of lesions have individual scores for induration, erythema, scaling, 
BSA and Pruritus (as described above) that average 4. 
5 
Very Severe 
Very marked plaque elevation, scaling, and/or erythema. 
Plaque elevation = very marked (very marked elevation typically with hard 
sharp edges) 
Scaling = very coarse (coarse, thick tenacious scale over most of all of the 
lesions; rough surface) 
Erythema = very severe (extreme red coloration; dusky to deep red coloration) 
Majority of lesions have individual scores for induration, erythema, scaling, 
BSA and Pruritus (as described above) that average 5.  
 
Efficacy Evaluation:  
Success = [Baseline (ISGA ≥2) – follow-up ISGA score] ≥ 2, meaning: 
• Patients with “mild” psoriasis become “clear”. 
• Patients with “moderate” psoriasis become “clear” or “almost clear”. 
• Patients with “severe” psoriasis become at least “mild”, if not “clear” or 
“almost clear”.  
• Patients with “very severe” psoriasis become at least “moderate” if not mild 
to clear. 
 
5.1.2 Target Lesion 
Pre-select two target lesions representative of the disease (for example: one from a 
refractory area, elbow or knee, while the other from the trunk) for separate variables, 
including induration, erythema, scaling, and BSA on a 6-point score. 
Take photographs and measure the severity and extent before the clinical intervention and 
at every visit. 
 
Effective (average of 2 Target Lesions) = [Baseline (Target Lesions≥2) - Target Lesions 

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score at end of treatment] ≥2. 
 
The response to TC Cream will be assessed relative to the placebo group (ratio of patients 
who achieved the efficacy goal).  
 
Table 7. Severity of Psoriasis Area Severity Index (PASI) at the Target Lesion Site  
Score  Grade  
Erythema  
Scaling  
Plaque Elevation  
0  
Clear  
No 
evidence 
of 
erythema  
No evidence of scaling  
No 
evidence 
of 
plaques above normal 
skin level  
1  
Almost 
Clear  
Pink 
discoloration, 
minimal erythema  
Occasional fine scales hardly 
noticeable  
Slight, just discernable 
elevation 
above 
normal skin level  
2  
Mild  
Light red coloration  
Slight but definite roughness, 
fine 
scale 
present, 
no 
cracking  
Discernable elevation 
above 
normal 
skin 
level 
upon 
examination, but not 
pronounced  
3  
Moderate  
Moderate redness, but 
not dark  
Moderate 
roughness, 
somewhat coarse scaling  
Definite 
plaque 
formation 
with 
rounded/sloped edges 
to plaque  
4  
Severe  
Dark red coloration  
Marked 
roughness, 
coarse/thick scaling, cracking 
may be evident  
Marked elevation with 
hard, distinct edges to 
plaque  
5  
Very 
Severe  
Very 
dark 
red 
coloration 
with 
induration present  
Very thick scales covering 
extensive 
area 
severe 
cracking/fissures 
may 
be 
evident  
Very 
marked 
elevation, very hard 
and sharp edges to 
plaque  
Note: Body Surface Area (BSA) percentage is no longer requested as an individual component sign in 
the PASI scale, but the BSA percentage and distribution should be recorded at baseline.  
 
5.1.3 Psoriasis Area and Severity Index (PASI) 
PASI is a physician-performed assessment of both the extent of psoriasis on the four body 
areas (head, trunk, upper limbs, and lower limbs) and the degree of plaque erythema, 
scaling, and thickness. The PASI score accounts for both the extent of BSA affected by 
erythema, scaling, and thickness, and the severity of erythema, ranging from 0 (no disease) 
to 72 (maximal disease). 
 
The proportion of subjects achieving PASI 75, defined as ≥ 75% improvement in PASI 
score from baseline at the end of 8 weeks of treatment, is the secondary efficacy endpoint 

Protocol Version: 00 
 
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in this study. 
(See attached PASI scoring template) 
 
5.1.4 Psoriasis Disability Index（PDI） 
The Psoriasis Disability Index questionnaire was developed by Cardiff University's 
Dermatology Department in Wales, UK, to assess quality of life in patients with Psoriasis. 
It is self-explanatory and can be handed to the patient to fill in, without the need for a 
detailed explanation. It is usually completed in three or four minutes 
 
Scoring (Visual Analogue Scale) 
The scoring of each question is answered on a graded scale from 0 to 6. If a question is 
left unanswered, the score taken is 0. The PDI is calculated by summing the scores of the 
fifteen questions, resulting in a maximum of 90 and a minimum of 0. The higher the score, 
the greater the impairment of quality of life. The PDI can also be expressed as a 
percentage of the maximum possible score of 90. 
 
Scoring (Tick-box method) 
The scoring of each question is answered on a series of 4 answers: not at all (scores 0), a 
little (scores 1), a lot (scores 2), very much (scores 3). If a question is left unanswered, the 
score taken is 0. The PDI is calculated by summing the scores of the 15 questions, 
resulting in a maximum of 45 and a minimum of 0. The higher the score, the greater the 
impairment of quality of life. The PDI can also be expressed as a percentage of the 
maximum possible score of 45. 
 
The PDI can be analyzed under five headings as follows 
 
 
VAS 
Tick-Box 
Daily Activities 
Questions 1，2，3，4，5 
Score max：30 
15 
Work or School or alternative questions 
Questions6，7，8 
Score max：18 
9 
Personal relationships 
Questions 9，10 
Score max：12 
6 
Leisure 
Questions 11，12，13，14 
Score max：24 
12 
Treatment 
Questions 15 
Score max：6 
3 
See attached PDI questionnaire. 
 
5.1.5 Dermatology Life Quality Index (DLQI) 
The Dermatology Life Quality Index (DLQI) is the most widely used measure for 
assessing quality of life related to skin disease in psoriasis trials. This tool consists of 10 
questions covering six domains (symptoms and feelings, daily activities, leisure, work and 
school, personal relationships, and trouble with psoriasis treatment). The response options 
range numerically from 0 to 3 points, with 0 indicating not affected at all and 3 indicating 
very much affected. This yields an overall score of 0–30 points, with lower scores 
indicating better quality of life. (See attached QLDI questionnaire.) 
 
Table 8. Dermatology Life Quality Index (DLQI) Scale Definition 

Protocol Version: 00 
 
21 
 
Score 
Definition 
0 to 1 
No impact 
2 to 5 
Mild impact 
6 to 10 
Moderate impact 
11 to 20 
Very large Impact 
21 to 30 
Extremely large impact 
 
5.2 Guidelines for Evaluation of Measurable Disease 
All measurements should be taken and recorded in metric notation using the supplied 9x9 
square ruler and camera. All baseline evaluations should be performed as close to the 
beginning of treatment as possible, and no more than 1 week before the beginning of 
treatment. 
 
The same assessment method and technique should be used to characterize each identified 
and reported lesion at baseline and during follow-up. 
 
6. SAFETY 
6.1 Expected Adverse Events 
In the multiple controlled randomized clinical trials conducted in China, the most frequent 
adverse experiences reported with TC Cream were mild skin pigmentation (mild color 
pigmentation, erythema); very few patients had mild chromatosis or photosensitivity. The 
symptoms will usually disappear with drug withdrawal. No severe adverse reactions were 
reported in the completed clinical studies.  
 
6.2 Adverse Event Definition and Classification 
An adverse event (AE) is defined as any untoward medical occurrence in a patient or 
clinical investigation subject administered a pharmaceutical product that does not 
necessarily have a causal relationship with the treatment. An AE can, therefore, be any 
unfavorable and unintended sign (including abnormal laboratory finding), symptom, or 
disease temporarily associated with the use of a medicinal (investigational) product, 
whether related to the medicinal (investigational) product. 
 
CTCAE term (AE description) and grade: The descriptions and grading scales found in the 
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for 
AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE 
version 4.0. 
 
A copy of the CTCAE version 4.0 can be downloaded from the CTEP website. 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/cTC.htm. 
 

Protocol Version: 00 
 
22 
 
6.3 Serious Adverse Event 
A serious adverse event (SAE) is defined as any adverse experience that results in any of 
the following outcomes: 
l Fatal 
l Life-threatening 
l Requires or prolongs hospitalization 
l Results in persistent or significant disability or incapacity； 
l A congenital anomaly or birth defect 
l An important medical event requires medical intervention to prevent one of the above 
outcomes. 
 
Important medical events are those that may not be immediately life-threatening but may 
jeopardize the subject and may require intervention to prevent one of the other serious 
outcomes listed above. Examples of such events are intensive treatment in an emergency 
room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that do not 
result in hospitalization. These adverse events will generally be considered serious by this 
criterion. 
 
Inpatient hospitalization or prolongation of existing hospitalization means that hospital 
inpatient admission and/or prolongation of hospital stay were required for treatment of the 
AE, or that they occurred because of the event. It does not refer to pre-planned elective 
hospital admission for treatment of a pre-existing condition that has not significantly 
worsened, or to diagnostic procedures.  
 
6.4 Laboratory and Other Safety Assessment Abnormalities Reported as AEs and 
SAEs 
The clinical investigator will review any abnormal laboratory changes and, if any 
additional action is taken (e.g., reducing the dose or stopping the drug), report the 
laboratory abnormality as an adverse event on an Adverse Event case report form. 
 
6.5 Pregnancy 
Any pregnancy occurring during the clinical study and the outcome of the pregnancy 
should be recorded and followed up for congenital abnormalities or birth defects. 
Pregnancy tests will be performed three times using test strips at pre-study -1 (or week 0), 
4, and 8. Birth control strategies should be used for age-bearing female patients. 
 
6.6 Severity of Adverse Events 
Adverse events will be classified according to the following severity scale: 
l Grade 1(Mild) - The adverse event is easily tolerated and does not interfere with daily 
activity. 
l Grade 2 (Moderate) - The adverse event interferes with daily activity, but the subject 

Protocol Version: 00 
 
23 
 
is still able to function. 
l Grade 3 (Severe) - The adverse event is incapacitating and requires medical 
intervention. 
 
6.7 Relationship to Study Drug 
Adverse events will be assessed for the relationship to the study drug (causality) 
according to the following scale: 
Unrelated - The event is independent of the study drug. 
Unlikely - The event may or may not follow a reasonable temporal sequence from 
drug administration and can plausibly be explained and/or attributed to something 
other than the study drug. 
Possible - The event follows a reasonable temporal sequence from drug 
administration, follows a clinically reasonable response on withdrawal, and is 
unlikely to be attributed to something other than the study drug. 
Probable - The event follows a reasonable temporal sequence from drug 
administration, follows a clinically reasonable response on withdrawal, and cannot 
be reasonably explained by something other than the study drug.  
    Definite - There is clear evidence to reveal causality, and other possible existing 
factors can be excluded. It follows a reasonable temporal sequence from the time of drug 
administration. It follows a known response pattern to the suspected drug. It disappears on 
cessation and recurs with reintroduction of the test drug.  
 
6.8 Procedures for Collecting Adverse Event Information 
Before subsequent drug administration(s), subjects will be questioned concerning unusual 
symptoms that may have occurred since the previous administration of the study drug(s). 
 
Any adverse events, whether serious or non-serious, will be monitored throughout the 
study and followed to resolution, when possible, regardless of whether the subject is still 
participating in the study. The investigator will remain on-call until the end of the study. 
 
6.9 Procedures for Reporting Adverse Events 
Subjects will be instructed to report any adverse events that may arise during the study to 
clinic personnel. 
 
All symptoms will be recorded and will be reviewed by the investigator before any 
subsequent drug administration. 
 
When appropriate, medical tests and examinations will be performed to document 
resolution of the event(s). 
 
Adverse events will be classified according to the MedDRA (Medical Dictionary for 

Protocol Version: 00 
 
24 
 
Regulatory Activities) and reported by severity, duration, relationship to the study 
medication(s), and action taken. 
 
All serious adverse events occurring during the study, whether considered to be related to 
the study drug, will be reported to Teva within 48 hours. SAE report(s) will be typed in 
English. 
These SAE reports will contain the following information: 
A. Study name/number 
B. Study Drug 
C. Investigator details (name, phone, fax, e-mail) 
D. Subject Number 
E. Subject Initials 
F. Subject Demographics 
G. Clinical Event 
1) Description 
2) Date of onset 
3) Treatment (drug, dose, dosage form) 
4) Relationship to study drug 
5) Action taken regarding the study drug 
H. If the AE was Fatal 
1) Cause of death (whether the death was related to the study drug) 
2) Autopsy findings (if available). 
The notification about any serious adverse event will be directed to the Sponsor.  
 
7. DROPOUT, WITHDRAWAL, AND TERMINATION 
If a subject’s participation is terminated prematurely, the cause for the early termination 
will be documented. 
 
Subjects will be free to drop out or withdraw at any time, for any reason, or they may be 
dismissed, if necessary, to protect their health or the integrity of the study. 
 
Subjects who experience worsening of their skin condition will be evaluated for continued 
participation in the study based on the potential impact of the TC Cream on the integrity 
of the study results and the current FDA guidelines. The evaluation will take place as 
soon as possible after the episode(s) occurred. 
 
Subjects who have a medical event equivalent to CTCAE grade 2 or higher infection that 
is deemed not suitable for continuation of the treatment may be considered to withdraw 
from the trial (as determined by the investigator). 
8. 
DATA MANAGEMENT 
8.1 Fill in CRF 

Protocol Version: 00 
 
25 
 
The case report form (CRF) is the primary data collection instrument for the study. All 
data requested on the CRF must be recorded.  All missing data must be explained. If a 
space on the CRF is left blank because the procedure was not done or the question was 
not asked, write “N/D”.  If the item is not applicable to the individual case, write “N/A”.  
All entries should be printed legibly in black ink. If any entry error has been made, to 
correct such an error, draw a single straight line through the incorrect entry and enter the 
correct data above it. All such changes must be initialed and dated. DO NOT ERASE, 
OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
8.2 
Data Entry and Amendment 
The data administrator, appointed by the sponsor, is responsible for data entry and 
management. All study data will be entered on the EpiData 3.1 Software. To vouch for the 
accuracy of the data, the data should be entered by two data entry staff to create duplicate 
copies, then the data administrator conducts proofing, scanning, and reporting on two 
copies of the database. 
 
For existing CRE questions, data management will produce a question-and-answer form 
and request it from the investigator through the clinical monitor. The investigator should 
answer the questions and return as quickly as possible. Data management conducts data 
amending, affirming, and inputting according to the investigator's responses. It could 
revert to a question-and-answer format if necessary. 
8.3 
Data Management Responsibilities 
All source documents and laboratory reports must be reviewed by the clinical team and 
data entry staff to ensure they are accurate and complete. Adverse events must be graded, 
assessed for severity and causality, and reviewed by the site PI or designee. 
Data collection is the responsibility of the clinical trial staff at the site under the 
supervision of the site PI. During the study, the investigator must maintain complete and 
accurate documentation. 
 
The Data Coordinating Center will serve as the Statistical and Data Coordinating Center 
for this study and will be responsible for data management, quality review, analysis, and 
reporting of the study data. 
9. 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
9.1 
Sample Size Assumptions 
The sample size of the investigational product must be up to 44 cases, and the placebo 
must be 44 cases (total sample size 88 cases). In this way, it can be deduced that the 
treatment group's efficiency is better than that of the placebo group, assuming a 90% 
single-sided testing efficiency.  
 
Assuming the missing cases are up to 20% because of regulating the intention–to–treat 

Protocol Version: 00 
 
26 
 
population, the sample size should be XXX by extended 20%, then taking an even integer 
for XXX cases, therefore the total sample size needs to include XXX cases, where XXX 
is for the treatment group, and XXX is for the placebo group. 
9.2 
 Data Analysis Considerations 
9.2.1 Efficacy Analysis Populations 
The populations include all patients who were randomized and received at least one dose 
of any study drug. 
9.2.2 Safety Analysis Populations 
The populations include all patients who were randomized and received at least one dose 
of any study drug. 
9.2.3 Analysis Data Sets 
A. Intention-to-treat (ITT) Analysis should be defined as all subjects randomized and 
dispensed medication. Subjects should not be excluded from the ITT population for 
dropping out or failing to follow the protocol. 
B. Safety Analysis Sets are performed for all patients who underwent randomization and 
received at least 1 dose of study medication. So, with or without a test record, patients 
who experience adverse events should be included in the statistical analysis if they 
have received at least one dose of the study medication. 
9.2.4 Analysis Plan 
The response to treatment with TC Cream will be assessed using an intention-to-treat 
(ITT) comparison with the placebo group (ratio of efficacy goals achieved). 
 
The statistical analysis will be performed using a two-sided t-test with a 95% confidence 
interval (CI) for the difference in response rates between the two treatment groups (ITT, 
TC vs. Vehicle). A P value < 0.05 is considered to be statistically significant.  
9.2.4.1 Efficacy Analyses 
The data will be summarized with descriptive statistics, including Demographics, baseline, 
and each efficacy endpoint. The measurement data will be described by its mean, standard 
deviation, minimum, and maximum, and the 95% confidence interval for the mean will be 
calculated. The enumeration data will be described by its frequency and percentage, and 
the 95% confidence interval of the percentage will be calculated. 
9.2.4.2  Safety Analyses 
The safety data will be summarized with descriptive statistics. 
 

Protocol Version: 00 
 
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10. ETHICAL AND REGULATORY REQUIREMENTS 
10.1 Investigator Responsibilities 
The investigator is responsible for ensuring that the clinical study is performed in 
accordance with the protocol, the current revision of the Declaration of Helsinki, current 
ICH and GCP guidelines, and applicable regulatory requirements. The investigator can 
delegate tasks to qualified designees. 
 
10.2 Ethical Review 
An investigator will not initiate a study without written approval from the Institutional 
Review Board (IRB). This protocol and the Informed Consent Form (ICF) will be 
reviewed and approved by the IRB prior to the initiation of the study. Any amendments to 
the protocol will also be reviewed by the IRB. A copy of the IRB’s approval 
documentation will be included in the final report. 
 
The IRB is constituted and operates in accordance with the principles and requirements 
described in the U.S. 21 CFR Part 56, and the ICH Harmonized Tripartite Guideline 
10.3 Informed Consent 
Written informed consent will be obtained from all patients or their legally authorized 
representative participating in this trial, as stated in the Informed Consent section of the 
Federal Regulations, Title 21, Part 50. If a patient’s signature cannot be obtained, for all 
patients under the age of 18, the investigator must ensure that the patient’s legally 
authorized representative signs the informed consent. Prior to signing the ICF, subjects 
will be allowed adequate time to consider the potential risks associated with their 
participation in the study. A copy of the signed ICF will be provided to the subject. 
Documentation of the consent process and a copy of the signed consent shall be 
maintained in the patient’s medical record. 
10.4 Confidentiality 
All documentation collected by the sponsor or by the investigator will be kept confidential 
and remain the property of the sponsor. 
10.5 Amendments and Protocol Revisions 
Amendments to the protocol or the ICF will be submitted to the IRB for approval. Any 
modification to this protocol will be documented as a protocol revision or amendment, 
signed by the principal investigator and approved by the IRB before the revision or 
amendment may be implemented. The only circumstance in which the amendment may be 
initiated without regulatory approval is for a change necessary to eliminate an apparent 
and immediate hazard to the patient. In such cases, the investigator must notify the IRB in 

Protocol Version: 00 
 
28 
 
writing within 10 working days after the implementation. PRIG confirms that any 
substantive major changes to the protocol will be notified to the FDA. 
 
For amendments to the protocol that alter the study design after the study has been 
initiated, the investigator and/or the sponsor will decide whether the subjects’ consent to 
continue participation is required. If an alteration is required to the ICF, subjects will be 
asked to sign the revised ICF at their next visit. 
10.6 Study Termination 
The sponsor (PRIG) reserves the right to terminate the study at any time. 
 
11. MONITORING OF THE STUDY 
11.1 On-Site Audits/Inspections 
Representatives of the sponsor will visit the clinical research facility to conduct an audit 
of the study in compliance with regulatory guidelines and company policy. Such audits 
will require access to all study records, study medication, and source documents (CRFs) 
for inspection and comparison. The sponsor will provide sufficient notice to the clinical 
facility prior to the visit to allow adequate preparation for the audit. 
 
Similar inspection procedures may also be conducted by agents of any regulatory body 
reviewing the results of this study in support of a New Drug Application. The clinical 
facility will immediately notify the sponsor if a regulatory agency contacts it regarding an 
upcoming inspection. 
 
11.2 Monitoring 
The sponsor or representative(s) of the sponsor may visit the study site to monitor the 
conduct of the study. The staff of the clinical facility will be available to assist the sponsor 
in answering any inquiries. 
 
During these monitoring visits, the subjects’ medical records, CRFs, and other 
study-related documents, including drug accountability records and study medications, 
will be made available for review. 
 
12. ARCHIVES/RECORD RETENTION 
The clinical facility will archive all study-related documents and retain test and reference 
products in accordance with applicable regulatory requirements. 
 
If the investigator(s) relocate or, for any reason, withdraw from the study, the study 

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records must be transferred to an agreed-upon designee, such as another institution, 
another investigator, or to Psoriasis Research Institute of Guangzhou, Guangdong, China 
(PRIG). Records must be maintained in accordance with PRIG or FDA requirements. 
 
13. REFERENCES 
1. Menter A, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis, section 3: 
Guidelines of care for the management and treatment of psoriasis with topical therapies J Am Acad 
Dermatol 2009, 60: 643-659. 
2 Lebwohl M．A clinician’s paradigm in the treatment of psoriasis．J Am Acad Dermato 2005, 153(1 
Suppl 1)：59-69． 
3 Greaves MW, Weinstein GP. Treatment of psoriasis. N Engl J Med 1995, 332:581–8. 
4 Gawkrodger DJ on behalf of the Therapy Guidelines and Audit Subcommittee of the British 
Association of Dermatologists. Current management of psoriasis. J Dermatolog Treat 1997, 8:27–55.