Clinical trial NCT04207801
Conditions: Chronic Plaque-type Psoriasis
Keywords: AUR101 Psoriasis
Sponsor: Aurigene Discovery Technologies Limited
Start date: 2020-01-21; Completion date: 2021-04-15
Enrollment: 90 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This will be a multicenter, double-blind, double-dummy, placebo controlled, randomized study to evaluate efficacy and safety of AUR101 (RORgamma inhibitor) in patients with moderate-to-severe psoriasis.

Approximately 90 patients with chronic moderate-to-severe plaque psoriasis will be randomized to the 2 dose groups of AUR101 and one group of Placebo. The patients will receive the treatment for 12 weeks.

Detailed description:
This will be a multicenter, double-blind, double-dummy, placebo controlled, randomized study to evaluate efficacy and safety of two doses of AUR101 in patients with moderate-to-severe psoriasis.

Approximately 90 patients with chronic moderate-to-severe plaque psoriasis (defined as Psoriasis Area and Severity Index (PASI) ≥12 and Body Surface Area (BSA) involved ≥10%) will be randomized to the 2 dose groups of AUR101 and placebo in the ratio of 1:1:1.

The patients in each arm will receive AUR101 of 400 mg twice daily or AUR101 600 mg twice daily or matching placebo twice daily for 12 weeks in a double blind, double dummy fashion.

Every patient will receive 12 weeks of treatment. All the patients will be followed up for 14 ± 2 days of their last dose for safety assessment.

A subset of approximately 25 patients, who consent, will be asked to come for plasma PK assessment in week 4 of dosing.

Efficacy evaluation will be done by PASI, DLQI and BSA assessment. Safety assessment will be done by AEs and regular lab assessment.

Arms: arm 1: 400 mg AUR101 twice daily arm 2: 600 mg AUR101 twice daily arm 3: Matching Placebo twice daily
Interventions: intervention 1: AUR101 intervention 2: Matching Placebo
Intervention descriptions: intervention 1: Inhibitor of RORγ intervention 2: Drug-Placebo of AUR101 tablet

Protocol documents:
Prot_000.pdf: 
 
CLINICAL TRIAL PROTOCOL 
 
A Phase II, Multicenter, Double-blind, Double-dummy, Placebo controlled, 
Randomized, Study to Evaluate the Efficacy and Safety of two doses of AUR101 
in patients with Moderate-to-Severe Psoriasis (INDUS-2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confidentiality Statement 
 
This document is the property of Aurigene Discovery Technologies Limited (subsidiary of Dr. Reddy’s 
Laboratories Limited). The information in this document contains trade secrets and commercial 
information that are privileged or confidential and may not be disclosed without the express written 
permission of Aurigene Discovery Technologies Limited, unless required by federal or state law or 
regulations. Any person to whom the information is disclosed must be informed that the information is 
privileged or confidential and may not be further disclosed by them. These restrictions on disclosure will 
apply equally to all future information supplied to you that is indicated as privileged or confidential. 
Trial Phase 
Phase II 
Protocol Number 
AUR101-201 
Investigational 
Product 
AUR101 (Inhibitor of RORγ) 
Sponsor 
Aurigene Discovery Technologies Limited 
(Subsidiary of Dr. Reddy’s Laboratories Limited) 
39-40, KIADB Industrial Area, Phase II, 
Electronic City Hosur Road, 
Bangalore- 560100, Karnataka, India 
Clinical Trial 
Protocol Version 
1.0 
Issue Date 
07 Aug 2019 




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PROTOCOL SIGNATURE PAGE 
 
Title of Study: A Phase II, Multicenter, Double-blind, Double-dummy, Placebo 
controlled, Randomized, Study to Evaluate the Efficacy and Safety of two doses of 
AUR101 in patients with Moderate-to-Severe Psoriasis (INDUS-2) 
 
I confirm that I have read, and I understand this protocol and other appropriate related 
documentation, including the Investigator’s Brochure for AUR101. I agree that the 
available nonclinical information on the investigational product and the clinical data 
from Phase I are adequate to support the proposed Phase II clinical trial. This study will 
be conducted in compliance with the clinical trial protocol approved by the EC/IRB 
overseeing the study at the Clinical Site. The study will comply with the International 
Conference for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and 
current revision of the Declaration of Helsinki. In addition, this study will be conducted 
in compliance with local regulatory and ethical requirements as well as US FDA 
guidelines and the New Drugs and Clinical Trials Rules, 2019 of the Department of 
Health and Family Welfare, India. I will also appropriately direct and assist the personnel 
at the trial site who will be involved in the conduct of the study. 
 
Principal Investigator or Clinical Site Investigator: 
 
Signature                                                                                                 Date 
______________________________________                             _________________ 
 
 
Name: 
 
Title: 
 
Name of the site: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1.0 
SYNOPSIS   
Sponsor:  Aurigene Discovery Technologies Limited 
Name of Study Therapy: AUR101 – An oral RORγT inhibitor for anti-inflammatory 
disorders  
Protocol ID: AUR101-201 
Title of Study: A Phase II, Multicenter, Double-blind, Double-dummy, Placebo 
controlled, Randomized, Study to Evaluate the Efficacy and Safety of two doses of 
AUR101 in patients with Moderate-to-Severe Psoriasis (INDUS-2). 
Study Centers: 15-25  
 
Phase of Development:  
Phase II 
Study Objectives:   
Primary:  
 To assess efficacy of AUR101 in patients with moderate-to-severe psoriasis  
Secondary:  
 To evaluate the safety and tolerability of two oral doses of AUR101 in patients 
with moderate-to-severe psoriasis  
 To evaluate the plasma pharmacokinetics of AUR101 in patients with moderate-
to-severe psoriasis  
 To evaluate effect of AUR101 on quality of life in patients with moderate-to-
severe psoriasis 
Study Design and Investigational Plan:   
This will be a multicenter, double-blind, double-dummy, placebo controlled, 
randomized study to evaluate efficacy and safety of two doses of AUR101 in patients 
with moderate-to-severe psoriasis  
 
• 
Approximately 90 patients with chronic moderate-to-severe plaque psoriasis 
(defined as Psoriasis Area and Severity Index (PASI) ≥12 and Body Surface 
Area (BSA) involved ≥10%) will be randomized to the 2 dose groups of 
AUR101 and placebo in the ratio of 1:1:1. 
• 
The patients in each arm will receive AUR101 of 400 mg twice daily or 
AUR101 600 mg twice daily or matching placebo twice daily for 12 weeks in a 
double blind, double dummy fashion. All the patients will be followed up for 14 
± 2 days of their last dose for safety assessment. 
• 
A subset of approximately 25 patients, who consent, will be asked to come for 
plasma PK assessment in week 4 of dosing.  
Inclusion Criteria  
1. Confirmed diagnosis of chronic plaque-type psoriasis, diagnosed at least 6 
months before screening 
2. Psoriasis of at least moderate severity, defined as PASI≥12 and involved 
BSA≥10 % at screening and Day 1  


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3. Adult males or females, ≥ 18 to ≤ 65 years of age,  
4. Ability to communicate well with the investigator and to comply with the 
requirements of the entire study  
5. Willingness to give written informed consent (prior to any study related 
procedures being performed) and ability to adhere to the study restrictions and 
assessments schedule. 
 
Exclusion Criteria: 
1. History of erythrodermic, guttate, or pustular psoriasis within last 12 months 
2. Efficacy failure on any biologic (e.g. interleukin (IL) -17 antibodies like 
brodalumab or ixekizumab or anti-TNF agents. like etanercept, infliximab or 
adalimumab) for the treatment of psoriasis  
Note: Efficacy failure is defined as: A) Failure to achieve static Physician/ 
Investigator Global Assessment (PGA/IGA) of 0 to 2 (i.e. clear to mild) despite a 
continuous treatment with biologic at the approved (as in package insert) dose 
for at least 8 weeks And / Or B) After having an efficacious response, PGA/IGA 
increased to 3 or higher while receiving the approved (as in package insert) dose 
as maintenance  
3. Static 5-point IGA mod 2011 scale of 0 to 2 at screening or Day 1. 
4. BMI ≥ 35 kg/m2 
5. Current treatment or history of treatment for psoriasis with IL-17 or IL-12/23 
antagonist biological agents (e.g. secukinumab, briakinumab, tildrakizumab, 
ustekinumab etc.) within 6 months prior to study day 1 
6. Current treatment or history of treatment for psoriasis with other biological 
agents (e.g. adalimumab, etanercept, infliximab, alefacept etc.) within 3 months 
prior to study day 1  
7. Current treatment or history of treatment for psoriasis with non-biological 
systemic medications (including systemic steroids, methotrexate, cyclosporine 
etc.) or phototherapy within 4 weeks prior to study day 1.  
8. Treatment with medicated topical agents (having active pharmaceutical 
ingredient that can impact the  interfere with effect of the study drug; See 
Section 8.11) within 2 weeks prior to study day 1. 
9. History or presence of any medical or psychiatric disease, or clinically 
significant laboratory / ECG abnormalities at screening, any or a combination of 
illnesses, which, in the opinion of the PI, may either put the patient at risk 
because of participation in the study, or influence the results or the patient's 
ability to participate in the study.  


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10. Evidence of organ dysfunction (e.g. liver dysfunction ≥ 1.5 X of ULN for ALT, 
AST or ALP or Total Bilirubin, or renal dysfunction of 1.5X of ULN of serum 
creatinine)  
11. Any surgery requiring general anesthesia within 3 months prior to screening 
12. Known or suspected history of alcohol or drug abuse, as judged by the 
investigator  
13. History or presence of malignancy except patients with non-melanoma skin 
cancer or carcinoma in situ of cervix who are allowed to participate in the study  
14. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface 
antigen (HBsAg), or hepatitis C antibodies (HCV Ab) at screening 
15. Patient with known past history of systemic tuberculosis or currently suspected 
or known to have tuberculosis 
16. Patient expected to be started on anti-tubercular therapy either for treatment or 
prophylaxis of tuberculosis 
17. Suspected tuberculosis infection as evident from a positive QuantiFERON TB-
Gold test (QFT) at screening. Patients with a positive QFT test may participate in 
the study if further work up as per the opinion of the investigator (like X-ray or 
CT scan or other locally acceptable method for diagnosing active tuberculosis) 
establishes that patient does not have active tuberculosis.  
18. History of hypersensitivity or idiosyncratic reaction to any investigational ROR-
gamma inhibitors or any of the excipients of study drug  
19. Any previous gastrointestinal surgery or recent (within 3 months) / current 
history of gastrointestinal disease, that in the opinion of investigator, could 
impact the absorption of the study drug 
20. Positive pregnancy test for women of child bearing potential (WOCBP) at the 
screening or randomization visit 
21. Male patients with partners of childbearing potential not willing to use reliable 
contraception methods. 
22. Pregnant or lactating women or WOCBP who are neither surgically sterilized 
nor willing to use reliable contraceptive methods (hormonal contraceptive, IUD 
or any double combination of male or female condom, spermicidal gel, 
diaphragm, sponge, cervical cap) 
23. Has received another new chemical entity/investigational drug within 28 days or 
5 half-lives of investigational drug (whichever is longer) prior to study day 1.   
24. Use of herbal remedies, mega dose vitamins (intake of 20 to 600 times the 
recommended daily dose) and minerals during the 2 weeks prior to the first 


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administration of investigational product. 
25. Patients who have received live or attenuated vaccine in the 4 weeks prior to 
study day 1. 
Outcome Measures 
 
Primary End-point 
1. Proportion of patients achieving PASI 75 response (i.e. 75% reduction from 
baseline PASI score) at the end of week 12.  
 
Secondary End-points: 
1. Proportion of patients achieving PASI 75 response (i.e. 75% reduction from 
baseline PASI score) at the end of week 4 and 8.  
2. Proportion of patients achieving PASI 50 response (i.e. 50% reduction from 
baseline PASI score) at week 4, 8 and 12.  
3. Proportion of patients achieving IGA 0 or 1 at week 4, 8 and 12. 
4. Percent change from baseline in PASI score at week 4, 8 and 12 
5. Change from baseline in IGA scale at week 4, 8 and 12 
6. Change from baseline to week 4, 8 and 12 in percent Body Surface Area 
(BSA) involved 
7. Change from baseline to week 4, 8 and 12 in Dermatology Life Quality Index 
(DLQI) 
Safety and tolerability Assessment 
1. Treatment Emergent Adverse Events (TEAEs), changes in vital signs, 
electrocardiograms (ECGs), laboratory assessments and physical examinations  
 
Pharmacokinetics  
Intensive PK will be done in a subset of approximately 25 patients at week 4 (±2 days) 
visit 
Time points: Pre-dose and 1, 3, 4, 5, 6, 8, 12 hours post-morning dose   
Efficacy criteria  
Total PASI score, IGA, DLQI will be measured at baseline (Day 1), weeks 2, 4, 6, 8, 
and 12. PASI and IGA efficacy endpoints will be evaluated both by the PI as well as by 
an independent dermatologist. For the primary endpoint, the assessment by the 
independent dermatologist will supersede the assessment by the PI. 
Safety Assessment will be done by evaluation of AEs/SAEs, changes in laboratory 


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parameters, ECG, vital signs and physical examination. 
Prohibited medication 
 Treatment 
with 
topical 
corticosteroid, 
topical 
vitamin 
D 
analogues, 
pimecrolimus, retinoids, salicylic acid, lactic acid, tacrolimus, tar, urea, α-
hydroxy or fruit acids 
 Treatment 
with 
systemic 
corticosteroids 
or 
non-steroidal 
systemic 
immunosuppressive 
or 
immunomodulator 
drugs 
(e.g., 
cyclosporine, 
methotrexate, mycophenolate-mofetil, azathioprine, etc.), phototherapy 
 Treatment with any drug, including any biological agents which can affect 
psoriasis 
 Any live virus vaccination 
Note: Only bland emollients will be allowed during the study participation. It means 
that all topical medications that contain pharmacologically active ingredients such as 
(but not limited to) lactic acid, salicylic acid, urea, α-hydroxy acids or fruit acids etc. 
will not be allowed during the study.  
If patient has received any of the above-mentioned therapy before randomization, 
adequate gap between initiation of study treatment and last dose of prohibited 
medication should be ensured as mentioned in exclusion criteria no. 5 to 8. 
Rescue Medication 
If patient’s PASI score increases by at least 50% from baseline level after at least 6 
weeks of therapy, patient can be given rescue medication as considered appropriate 
according to investigator. In other situations, if medically necessary (i.e. to control 
intolerable psoriasis symptoms), rescue treatment for psoriasis may be provided to study 
patients at the discretion of the investigator after discussion with sponsor medical 
monitor. In addition, even within first 6 weeks of therapy, if a patient has intolerable 
symptoms from psoriasis, then rescue medications can be administered. The investigator 
can choose any available medication as rescue medication to treat psoriasis. In this case, 
investigator should discuss with sponsor medical monitor. 
For the purpose of efficacy analysis, patients who receive rescue treatment during the 
study treatment period will be considered treatment failures with the last efficacy 
assessment deemed as Last Observation Carried Forward (LOCF) for the primary 
endpoint and other secondary efficacy endpoints relevant at other future time-points. 
Investigators should make every attempt to conduct efficacy and safety assessments 
(e.g. disease severity scores, safety labs) immediately before administering any rescue 
treatment. An unscheduled visit may be used for this purpose if necessary. Patients who 
receive “Rescue Medication” will be discontinued from the trial. All such patients 


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should be followed up after 14 ±2 days of study drug discontinuation for safety 
assessment. 
Statistical Analysis 
Sample Size 
AUR101 doses will be tested versus placebo with respect to the primary endpoint 
(PASI75 response). A sample size of 25 in each of the three arms will provide an 80% 
power with a one-sided Type I error of 0.05, if the true placebo response rate is 7% and 
the response rate on investigational arm(s) is 35%. The sample size is increased to 30 to 
account for ~ 15-20% drop outs over the study period.  
 
Data analysis 
 
The Safety Population includes all patients in the study who receive at least one dose of 
AUR101.  Efficacy population will include patients who do not have any major protocol 
or inclusion/exclusion violations, have a valid baseline and at least one post-baseline 
(follow up) assessment for PASI score (i.e. primary end-point) by the independent 
dermatologist. The Pharmacokinetic Population includes all patients in the study who 
receive any dose of AUR101 and provide samples for PK analysis. 
 
For efficacy, safety and PK analysis, data will be summarized using descriptive statistics 
(number of patients, mean, median, standard deviation, minimum, and maximum) for 
continuous variables and using frequencies and percentages for discrete variables. Data 
will be presented by treatment arms. 
 
For the efficacy analysis, appropriate statistical test will be applied to compare AUR101 
treatment arms with placebo. 
A comprehensive statistical analysis plan (SAP) will be finalized prior to final data 
analysis.  
In addition, interim analysis may be done after 45 patients complete 12 weeks of 
treatment to evaluate early trends of efficacy or safety without affecting individual 
patient’s blinding. A separate interim analysis plan will be prepared accordingly. 
 
 


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2.0 
LIST OF ABBREVIATIONS AND DEFINITION OF TERM 
 
AE 
Adverse Events 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
AUC 
Area under the plasma concentration 
AUC0-∞ 
Area under the plasma concentration-time curve from time 0 to 
infinity 
AUC0-t 
Area under the plasma concentration-time curve from time 0 to 
t hours calculated using the linear trapezoidal rule  
AUClast 
Area under the plasma concentration-time curve from time 0 to 
the last measurable concentration at time (t) calculated using 
the linear trapezoidal rule 
Beta-HCG 
Beta-Human Chorionic Gonadotropin 
BCRP 
Breast Cancer Resistant Proteins 
BID 
Twice daily 
BMI 
Body Mass Index 
BSA 
Body Surface Area 
BUN 
Blood Urine Nitrogen 
CI 
Confidence Interval 
CL/F 
Plasma Clearance 
Co-I 
Co-Investigator 
CDSCO 
Central Drugs Standard Control Organization  
Cmax 
Maximum plasma drug concentration from plasma concentration 
time profile 
CRF 
Case Report Form 
CT  
Computerized tomography 
CYP 
Cytochromes P450 
DCGI 
Drugs Controller General of India 
DBL 
Data Base Lock  
DLQI 
Dermatology Life Quality Index 
DLT 
Dose Limiting Toxicity 
ECG 
Electrocardiogram 
eCRF 
FDA 
electronic Case Report Form 
Food and Drug Administration 
FIH 
First in Human  
FTIH 
First Time in Human 
GCP 
Good Clinical Practice 
GGT 
Gamma-Glutamyl Transpeptidase 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice  
HBsAg 
Hepatitis B Surface Antigen 
HCV Ab 
Hepatitis C Virus Antibody 


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HED 
Human Equivalent Dose 
HIV 
Human Immunodeficiency Virus 
ICF 
Informed Consent  
ICH 
International Conference on Harmonization 
IGA 
Investigator Global Assessment 
IL-17 
Interleukin-17 
IL-23 
Interleukin-23 
IRB/ EC 
Institutional Review Board /Ethics Committee  
IUD 
Intrauterine Device 
IWRS 
Integrated Web based Randomization system 
Kel 
Elimination Rate Constant 
LOCF 
Last Observation Carried Forward 
MAD 
Multiple Ascending Dose 
MCH 
 Mean Corpuscular Hemoglobin  
MedDRA 
Medical Dictionary for Regulatory Activities  
NOAEL 
No-Observed-Adverse-Effect Level 
PASI 
Psoriasis Area and Severity Index 
PD 
Pharmacodynamics 
PGA 
Physician Global Assessment 
P-gp 
P-glycoprotein 
PI 
Principal Investigator  
PK 
Pharmacokinetics 
PO 
Per oral  
QD 
Once a day 
QFT 
QuantiFERON TB-Gold test 
RORγ 
Retinoic Acid Related Orphan Receptor Gamma 
SAD 
Single-Ascending Dose 
SD 
Standard Deviation 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOC 
System organ class 
t½ 
Terminal elimination half-life 
TEAEs 
Treatment emergent adverse events 
TGF 
Transforming Growth Factor 
TNF 
Tumor necrosis factor 
Th 
Helper T cells 
Tmax 
Time to reach Cmax 
ULN 
Upper Limit of Normal  
US 
United States of America 
WBCs  
White blood cells  
WHO 
World Health Organization 
WHO-DD 
World Health Organization Drug Dictionary 


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WOCBP 
Women of Childbearing Potential 


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TABLE OF CONTENTS 
CLINICAL TRIAL PROTOCOL .......................................................................................... 1 
1.0 
SYNOPSIS .................................................................................................................... 4 
2.0 
LIST OF ABBREVIATIONS AND DEFINITION OF TERM ........................... 10 
3.0 
INTRODUCTION ..................................................................................................... 18 
3.1 
Background ............................................................................................................ 18 
3.2 
Summary of Nonclinical Experience .................................................................. 19 
3.2.1 Nonclinical development ................................................................................... 19 
3.2.2 Summary of Pharmacokinetics ........................................................................ 19 
3.2.3 Nonclinical Safety and Toxicology studies ..................................................... 20 
3.3 
Summary of Clinical Experience .......................................................................... 21 
3.4 
Rationale for Current Study ................................................................................ 25 
3.4.1 Basis for Dose Selection ........................................................................................ 26 
3.4.2 Basis for Placebo controlled study........................................................................ 27 
4.0 
OBJECTIVES ............................................................................................................ 28 
4.1 
Primary Objective .................................................................................................. 28 
4.2 
Secondary Objectives............................................................................................. 28 
5.0 
ENDPOINTS .............................................................................................................. 28 
5.1 
Primary Endpoint ................................................................................................. 28 
5.2 
Secondary Endpoint .............................................................................................. 28 
6.0 
STUDY DESIGN ....................................................................................................... 28 
6.1 
Overview ................................................................................................................. 29 
6.2 
Number of Patients and Duration of Treatment ............................................... 29 
6.3 
Formulation and Mode of Administration ......................................................... 29 
6.4 
Schedule of Visits and Assessments ..................................................................... 29 
6.4.1 Screening Visit (Up to Day -14) ........................................................................... 29 
6.4.2 Visit 2: Randomization Visit (Day 1) .................................................................. 30 
6.4.3 Treatment Visits (Visits 3-7) ................................................................................ 31 
6.4.4 Follow up visit (Visit 8) ......................................................................................... 31 
7.0 
STUDY ENROLLMENT AND WITHDRAWAL .................................................. 32 
7.1 
Inclusion Criteria .................................................................................................. 32 
7.2 
Exclusion Criteria ................................................................................................. 32 
7.3 
Withdrawal of Patients from Study Treatment................................................. 34 
7.4 
Withdrawal Procedures ........................................................................................ 35 
7.5 
Replacement of Withdrawals ............................................................................... 35 
7.6 
Early Study Termination ...................................................................................... 35 
8.0 
INVESTIGATIONAL PRODUCT........................................................................... 35 


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8.1 
Description: ............................................................................................................ 35 
8.2 
Supply and Storage ................................................................................................ 36 
8.3 
Blinding ................................................................................................................... 36 
8.4 
Randomization ....................................................................................................... 37 
8.4.1 Preparation of randomization code ...................................................................... 37 
8.4.2 Randomization of patients .................................................................................... 37 
8.4.3 Breaking the randomization code......................................................................... 37 
8.5 
Dispensing ............................................................................................................... 38 
8.6 
Method of Administration ..................................................................................... 38 
8.7 
Compliance ............................................................................................................. 38 
8.8 
Accountability ........................................................................................................ 38 
8.9 
Treatment of Overdose .......................................................................................... 38 
8.10 
Prior and Concomitant Medications .................................................................... 39 
8.11 
Prohibited Concomitant Medications .................................................................. 39 
8.12 
Permitted therapy for psoriasis ............................................................................ 40 
8.13 
Rescue Medication ................................................................................................. 40 
8.14 
Contraception Methods ......................................................................................... 40 
8.15 
Drug Interactions/Precautions .............................................................................. 41 
9.0 
STUDY ASSESSMENTS .......................................................................................... 41 
9.1 
Demographics and Medical History ..................................................................... 41 
9.2 
Safety and Tolerability Assessments .................................................................... 41 
9.2.1 Adverse Events .................................................................................................... 41 
9.2.2 Physical Exam and Vital Signs ............................................................................ 42 
9.2.3 Clinical Laboratory Test ...................................................................................... 42 
9.2.4 Electrocardiogram ................................................................................................ 43 
9.3 
Efficacy Evaluations .............................................................................................. 43 
9.3.1 Psoriasis Area and Severity Index (PASI) ........................................................... 43 
9.3.2 Investigator Global Assessment (IGA) ................................................................ 44 
9.3.3 Dermatology Life Quality Index (DLQI) ............................................................ 45 
9.3.4 Photograph of the lesions ..................................................................................... 45 
9.4 
Pharmacokinetics Assessments ............................................................................. 46 
9.4.1 Blood sampling .................................................................................................... 46 
9.5 
Sequence of Assessments ....................................................................................... 46 
10.0 
ADVERSE EVENTS ................................................................................................. 47 
10.1 
Definition of Adverse Event .................................................................................. 47 
10.1.1 Recording and follow-up ................................................................................... 48 


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10.1.2 Procedures for reporting SAEs ......................................................................... 49 
10.1.3 Reporting to the IRB / ECs ............................................................................... 49 
10.1.4 Reporting to the Regulatory Agency ................................................................ 49 
10.2 
Pregnancy Reporting ............................................................................................. 49 
11.0 
DATA MANAGEMENT AND STATISTICAL ANALYSIS ................................ 50 
11.1 
Sample Size Calculation ........................................................................................ 50 
11.2 
Data Handling ........................................................................................................ 50 
11.3 
Analysis Sets ........................................................................................................... 50 
11.3.1 Safety Population ............................................................................................... 50 
11.3.2 Efficacy Population ............................................................................................ 51 
11.3.3 Pharmacokinetic Population ............................................................................. 51 
11.4 
Description of Statistical Analyses ....................................................................... 51 
11.4.1 General Considerations ..................................................................................... 51 
11.4.1.1 
Medical history ........................................................................................... 51 
11.4.1.2 
Prior and concomitant medication ........................................................... 51 
11.4.1.3 
Handling of missing values ........................................................................ 51 
11.4.2 Demographics and Baseline Characteristics ................................................... 52 
11.5 
Efficacy Analysis .................................................................................................... 52 
11.6 
Pharmacokinetic Analysis ..................................................................................... 52 
11.7 
Safety Analysis ....................................................................................................... 52 
11.7.1 Adverse Events ................................................................................................... 52 
11.7.2 Vital Signs and ECG .......................................................................................... 53 
11.7.3 Clinical Laboratory Tests.................................................................................. 53 
11.8 
Interim Analysis ..................................................................................................... 53 
12.0 
STUDY ADMINISTRATION .................................................................................. 53 
12.1 
Case Report Forms and Source Documentation ................................................. 53 
12.2 
Investigator Documentation .................................................................................. 54 
12.3 
Record Retention ................................................................................................... 54 
12.4 
Audit and Inspection Procedures ......................................................................... 54 
12.5 
Protocol Deviations and Amendment................................................................... 55 
12.6 
Sponsor Monitoring ............................................................................................... 55 
12.7 
Publication/Data Sharing Policy ........................................................................... 55 
12.8 
Reports and Publications ...................................................................................... 56 
13.0 
ETHICS/PROTECTION OF HUMAN PATIENTS .............................................. 56 
13.1 
Ethical Conduct of the Study ................................................................................ 56 
13.2 
Institutional Review Board (IRB)/Ethics Committee (EC) ................................ 56 
13.3 
Informed Consent .................................................................................................. 57 


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13.4 
Confidentiality and Data Protection .................................................................... 57 
14.0  REFERENCES ........................................................................................................... 59 
Appendix A: Pharmacovigilance Contact Details ............................................................... 62 
Appendix B: Clinical Laboratories and Other Departments and/or Facilities 
Participating in the Study ..................................................................................................... 63 
 
                                                         LIST OF TABLES 
Table 1: Study Activities ....................................................................................................... 17 
Table 2: Key PK parameters from MAD cohorts ............................................................... 23 
Table 3: Key PK parameters from Comparative PK Cohort ............................................ 24 
Table 4: Summary of Safety margin calculation based on NOAEL exposure in animals 
and MAD exposure in humans ............................................................................................. 27 
Table 5: Study drug administration according to treatment arms ................................... 37 
Table 6: List of Clinical Laboratory Tests .......................................................................... 42 
Table 7: PASI Score ............................................................................................................... 43 
Table 8: The IGA mod 2011 rating scale [28]........................................................................ 45 
 
LIST OF FIGURES 
 
Figure 1: Schematic presentation of mechanism of action of AUR101............................. 19 
Figure 2: Plasma concentration profile of AUR101 suspension (Period 1) vs. AUR101 
film coated tablet (Period 2) in Comparative PK part ....................................................... 25 
Figure 3: Mean IL-17 secretion in MAD cohorts ................................................................ 25 
 
 
 


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Table 1: Study Activities  
Assessment 
Screening 
visit 
(Up to  
Day -14) 
Treatment Period 
Follow-up 
visit:  14 ± 
2 days 
after last 
dose 
Visit 2: 
Random
ization 
visit 
(Day 1) 
Visit 3: 
Week 
2 ±2 
days 
Visit 4: 
Week 4 
±2 days 
 
Visit 5: 
Week 
6± 2 
days 
Visit 6: 
Week 8 
±2 days 
Visit 7 
(End of 
Treatme
nt): 
Week 12 
±4 days 
Informed Consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Height (Only at 
Screening), BMI (only at 
screening), weight 
X 
X 
 
X 
 
X 
X 
 
Medical history 
X 
X 
X 
X 
X 
X 
X 
X 
Menstrual history in 
females 
X 
 
 
 
 
 
 
 
Prior/concomitant 
medication check 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs a 
X 
X 
X 
X 
X 
X 
X 
X 
QuantiFERON TB-Gold 
testb 
X 
 
 
 
 
 
 
 
Inclusion & exclusion 
criteria check 
X 
 
 
 
 
 
 
 
Inclusion & exclusion 
criteria verification 
 
X 
 
 
 
 
 
 
12 lead ECG  
X 
 
 
 
 
 
 
X 
Randomization 
 
X 
 
 
 
 
 
 
Photographs of lesions  
 
X 
X 
X 
X 
X 
X 
X 
Blood sampling for PKc 
 
 
 
X 
 
 
 
 
Clinical laboratory tests 
(Haematology, 
Biochemistry)  
X 
X 
 
X 
 
X 
X 
X 
Urinalysis 
 
X  
 
 
 
 
X  
 
Viral Serology 
X 
 
 
 
 
 
 
 
PASI score, IGA by 
independent evaluator and 
Investigator 
X 
X 
X 
X 
X 
X 
X 
X 
DLQI  
 
X 
X 
X 
X 
X 
X 
X 
IP dispense d 
 
X 
X 
X 
X 
X 
 
 
IP return and compliance 
check   
 
 
X 
X 
X 
X 
X 
 
AE check 
 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test e 
X 
X 
 
X 
 
X 
X 
X  
AE = adverse event; ECG = electrocardiogram; PK = pharmacokinetic, IP= Investigational product, PASI= 
Psoriasis Area and Severity Index, IGA= Investigator Global Assessment 
aVital signs include body temperature, blood pressure and pulse rate 
b Patients who are positive by QuantiFERON TB- Gold test, should undergo further workup according to 
investigator opinion (like Chest X-ray, CT scan of chest or any other locally acceptable method) to rule out 
active tuberculosis.  
c Only in subset of approximately 25 patients  
d As directed by IWRS; IP may be dispensed on additional or fewer days, as required by logistics 
e Serum pregnancy test at screening, and urine pregnancy test at other visits will be done for women of child 
bearing potential only 


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3.0 
INTRODUCTION 
3.1 
Background 
 
 
Helper T cells (Th) have traditionally been divided into Th1 and Th2 subtypes. It was 
subsequently demonstrated that the third major Th cell class exists which was shown to 
be dependent upon interleukin 23 (IL-23) stimulation and produces IL-17 in response to 
antigen recognition, hence it was named Th17.[1, 2] The differentiation of this cell type 
and the consequent production of IL-17 is dependent upon the transcription factor 
Retinoic acid related orphan receptor gamma (RORγ). RORγ, together with its close 
neighbors RORα and RORβ, are considered orphan receptors where no single 
endogenous ligand has yet been identified, though several nonspecific oxy-sterols have 
been shown to bind and modulate RORγ transcription.[3-5] Among all the RORs, the 
subtype RORα is expressed in the liver, skeletal muscle, skin, lungs, adipose tissue, 
kidney, thymus, and brain, RORβ  predominantly in the brain and liver, and RORγ is 
highly expressed in the thymus, but significant expression is also found in the liver, 
skeletal muscle, adipose tissue, and kidney.[3]  
Different studies suggest a causative involvement of  IL-23 immune axis and Th17 
cytokines in different autoimmune diseases such as psoriasis, ankylosing spondylitis, 
psoriatic arthritis, atopic dermatitis, Crohn's disease, ulcerative colitis, multiple sclerosis, 
and non-infectious uveitis.[6-8] RORγ is therefore expected to have a central role in 
driving these pathologies. Clinical validation of the IL-17 pathway is already proven 
from the therapeutic efficacy of antibodies that neutralize Th17-associated cytokines and 
receptors (Secukinumab, Ixekizumab-IL-17, Ustekinumab-IL12/23, Guselkumab, 
Tildrakizumab-IL23 and Brodalumab-IL-17 receptor A) in moderate to severe psoriasis 
and other autoimmune disorders such as psoriatic arthritis and ankylosing spondylitis).[6, 
7, 9] In view of all these, reducing IL-17 via inhibition of RORγ is also expected to add 
clinical value in these diseases. 
A small molecule of RORγ could have multiple benefits over neutralizing antibodies for 
patients. As RORγ inhibitor reduces secretion of IL-17 as compared to only neutralizing 
circulating IL-17, hypothetically it may have better effect in disease pathology. Oral 
administration is generally preferred over the parenteral routes of administration required 
for antibodies, considering chronic nature of autoimmune disorders. It also offers the 
possibility to adjust dose in response to the therapeutic effect. In addition, the more rapid 
clearance and smaller half-life of orally administered small molecules allow for easier 
management of adverse events, like infectious complications, by getting the drug cleared 
from the body more quickly upon discontinuation.  
 
Mechanism of AUR101 
AUR101 is an inhibitor of RORγ, which is essential for the development of Th17 cells in 
the thymus.[10] When naive undifferentiated T cells first encounter a specific antigen, 
presented to them by a dendritic cell, they become activated and simultaneously receive 
signals directing them to differentiate into a specific class of T helper cells. IL-23 
secreted by macrophage and dendritic cells together with other cytokines such as 
Transforming Growth Factor (TGF) β and IL-6 promotes differentiation of helper T cells 
into Th17 cells. Th17 cells mainly up-regulate RORγ[9] and gain the ability to produce 
IL-17A, IL-17F, IL-21, IL-22 and other proinflammatory effector cytokines.[11-13] 


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AUR101 is a small molecule inhibitor of RORγ. By inhibiting RORγ, it reduces 
differentiation of naïve T cells to Th17 cells and subsequently secretion of various 
proinflammatory cytokines, predominantly IL-17.  
 
 
Figure 1: Schematic presentation of mechanism of action of AUR101  
 
3.2 
Summary of Nonclinical Experience 
3.2.1 
Nonclinical development 
As discussed in Section 3.1, the RORγ is a key transcription factor that is required for the 
development and differentiation of Th17 cells. AUR101 has demonstrated dose-
dependent inhibition of Th17 cells development and differentiation of both human and 
mouse in Th17 differentiation assays as determined by IL-17A production.  
The efficacy of AUR101 has also been evaluated in two preclinical models of psoriasis. 
In Imiquimod induced psoriasis model oral AUR101 administration at 10 mg/kg to 150 
mg/kg BID dose showed significant reduction in ear swelling at all test dosages. The 
maximal efficacy was observed at 75 mg/kg BID dose with 29% reduction in ear 
swelling with corresponding 37% reduction in ear skin histopathology score and 34% 
reduction in back skin swelling with corresponding 33% reduction in histopathology 
score. In a separate IL-23 induced psoriasis model, oral administration of AUR101 
showed significant reduction in ear skin swelling at all test dosages (18%, 28%, 42 % at 
3, 10, 30 mg/kg BID respectively) with corresponding reductions in ear skin 
histopathology scores of 35%, 43%, and 56%, respectively. The maximal efficacy 
observed in both the models (AUR101 75 mg/kg BID in Imiquimod induced psoriasis 
and 30 mg/kg BID in IL-23 induced psoriasis) are comparable with anti-IL-17A antibody 
administration in mouse. 
3.2.2 
Summary of Pharmacokinetics 
Psoriasis, 
Rheumatoid arthritis 
Uveitis, 
Autoimmune disorders 
 


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Pharmacokinetics of AUR101 has been determined in male mice, rats, dogs and 
monkeys. The dose normalized absolute oral bioavailability of AUR101 in mice, rats, 
dogs and monkeys ranged from 89% to 100%. The volume of distribution at steady state 
was greater than whole blood volume indicating distribution of the compound into 
extravascular space in the tested species. The terminal elimination half-life after oral 
administration ranged from a low of 0.96 h in rats to a high of 6.30 h in dogs. Food 
administration has not shown any effect on the systemic availability of the compound in 
mice and rats. Intravenously and orally administered AUR101 in rat showed minimal 
excretion though urine and faces suggesting that metabolism is the primary route of 
elimination. 
3.2.3 
Nonclinical Safety and Toxicology studies 
Non-clinical toxicology studies have been conducted with AUR101 for 2-weeks as well 
as 13-weeks in Wistar rats and Beagle dogs, and the current toxicological evaluation for 
AUR101 supports clinical studies for up to 13 weeks.  
In the 2-week GLP repeat dose study in Wistar rats, daily doses of 0 (vehicle), 100, 
300, 600, and 1000 mg/kg/day were utilized. There were no adverse clinical signs of 
toxicity observed during the treatment or the recovery period. There were no adverse 
changes in any of the clinical pathology parameters either.  
In the 13-week GLP repeat dose study in Wistar rats, doses of 0 (vehicle), 70, 150 and 
450 mg/kg/day were utilized. There was no mortality in the study. AUR101 related but 
non-adverse clinical signs included transiently observed mild salivation at all the tested 
doses during the treatment period, a localized or generalized alopecia in the ventral parts 
of the body in 450 mg/kg/day dose group and a mild abdominal distension at 450 
mg/kg/day in a few animals. These clinical signs gradually recovered to normalcy in all 
animals during the recovery period and are considered non-adverse. No AUR101 related 
neurobehavioral or ocular abnormalities were observed. There were no AUR101 related 
adverse changes in any of the laboratory parameters. Based on the results, the NOAEL in 
Wistar rats is considered to be 450 mg/kg/day. 
In the 2-week GLP repeat dose study in Beagle dogs, animals received daily doses of 0 
(vehicle), 25, 50 and 100 mg/kg/dose, BID which is equivalent to 0, 50, 100 and 200 
mg/kg/day for control, low, mid and high dose groups, respectively. Because of overt 
signs of toxicity during first 5 days of treatment, the high dose was reduced from 200 
mg/kg/day (100 mg/kg/dose, BID) to 150 mg/kg/day (75 mg/kg/dose, BID) from Day 6 
onwards. There were no mortalities in any of the AUR101 treated groups. Clinical 
observations were generally limited to 200/150 mg/kg/day dose group which exhibited 
reduced food consumption, reduction in body weight, decreased activity, soft stool, 
salivation, tremors and emesis. In the mid dose groups, emesis was infrequently observed 
only at some occasions. There were no test article-related ophthalmologic changes. No 
adverse or biologically significant changes in body temperature, quantitative or 
qualitative ECG parameters, blood pressure or respiration rate were observed. All the 
findings noticed during the treatment period were reversed to normalcy during treatment 
free period. Test article related changes in clinical pathology was limited to increased 
ALT in both genders; and AST, ALP, GGT and total bilirubin in males of high dose 
group (200/150 mg/kg/day). In conclusion, oral administration of AUR101 to male and 


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female Beagle dogs at 50 as well as 100 mg/kg/day followed by a 14-day recovery period 
was well tolerated and did not result in mortality or any adverse changes. Treatment 
related adverse findings were noted at 200→150 mg/kg/day, including severe clinical 
signs, body weight losses, low food consumptions, and remarkably increased ALT and 
AST. Based on the results, the NOAEL in this study is considered to be 100 mg/kg/day. 
In the 13-week repeat dose GLP study in Beagle dogs, doses of 0 (vehicle), 10 mg/kg 
BID, 30 mg/kg BID, or 60→50→40 mg/kg BID were utilized. Due to observed toxicity, 
the dosage of the high dose group (Group 4) was reduced from 60 mg/kg BID to 50 
mg/kg BID on Day 8 for both sexes, and then further reduced to 40 mg/kg BID from Day 
34 after a 5-day dosing holiday from Day 29 to Day 33. It is referred as 60→50→40 
mg/kg BID group. There was no mortality in the study. At 10 mg/kg BID and 30 mg/kg 
BID dose groups, there were no adverse clinical signs or changes in body weight and 
food consumption. The observed clinical signs at 10 and 30 mg/kg BID dose group were 
either transient or of lower magnitude. At 60→50→40 mg/kg BID dose, AUR101 related 
clinical signs included inappetence, prostration, decreased activity, salivation, thinness, 
tremors, cold to touch, unkempt fur, abnormal stool, vomitus, ocular discharge, ptosis, 
and/or pale gums during the dosing period, but were resolved at the end of the recovery 
period. Increases in liver enzymes (AST/ALT) occurred at 30 mg/kg BID as well as at 
60→50→40 mg/kg BID. However, the increase at 30 mg/kg BID was mild and 
reversible and considered non-adverse.  The majority of clinical signs noted at 
60→50→40 mg/kg BID as well as increase in liver enzymes in this dose group were 
considered adverse due to the high frequency and/or severity. Consequently, the 
no-observed-adverse-effect level (NOAEL) in dogs is considered to be 30 mg/kg/dose 
BID (i.e. 60 mg/kg/day). 
In addition to above toxicology studies, the genetic toxicity assessment of AUR101 has 
also been investigated. Results of an in vitro Bacterial Reverse Mutation Test have 
indicated that AUR101 is non-mutagenic. Similarly, the results of an in vivo 
micronucleus test in Wistar rats and in vitro chromosomal aberration test in human 
peripheral lymphocytes have indicated that AUR101 does not induce clastogenicity.  
3.3 Summary of Clinical Experience 
First Time in Human (FTIH) Phase I study (AUR101-101) has been completed at 
CMAX, a Phase I unit in Adelaide, Australia. This was a randomized, placebo-controlled 
study and included Single Ascending Dose (SAD) followed by Multiple Ascending Dose 
(MAD) cohorts among healthy volunteers. The study evaluated safety, tolerability, 
pharmacokinetics and pharmacodynamic (IL-17 inhibition) effects, and included 4 SAD 
cohorts (31 subjects; 23 active and 8 placebo), 3 MAD cohorts (24 subjects; 18 active 
and 6 placebo) and an open label Comparative PK part (6 subjects). The maximum dose 
evaluated is 600 mg BID for 14 days. 
  
The study was initiated with enteric coated AUR101 or placebo tablets in SAD cohorts.  
First 3 SAD cohorts were completed with enteric coated formulation at 100, 300 and 600 
mg respectively. The pharmacokinetic data from the first 3 SAD cohorts, done with 
enteric coated AUR101 tablets, were deemed inadequate with no dose-dependent 
increase in exposures and a highly variable half-life. Since pre-clinical investigation also 
showed that AUR101 absorption is expected to be largely from stomach, it was decided 
to test instant release AUR101 formulation (AUR101 suspension) by dissolving 


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AUR101 enteric coated tablet in water in SAD Cohort 4. SAD Cohort 4 (at 600 mg) also 
studied the Food Effect with AUR101 suspension. AUR101 or matching placebo 
suspension was then evaluated in MAD cohorts at 500 mg QD x14 days, 1000 mg x14 
days and at 600 mg BID x14 days.  
 
As desirable PK and PD was observed with AUR101 suspension, it was decided to take 
forward instant release formulation for further clinical development. Therefore, instant 
release film coated (i.e. non-enteric coated) AUR101 tablet formulation was prepared to 
improve patient compliance and ease of administration instead of preparing suspension 
on daily basis. An open label comparative PK part has also been done in 6 subjects to 
compare the PK of AUR101 suspension with the PK of AUR101 film coated tablet. In 
total, 47 subjects have received active AUR101 (23 in SAD, 18 in MAD and 6 in 
Comparative PK part) and 14 subjects (8 in SAD and 6 in MAD) have received placebo 
in the FIH Phase 1 study (INDUS). 
 
The study did not reveal any clinically relevant hepatic, renal, cardiac, respiratory, or 
neurological adverse events at any of the dosages in SAD. MAD and Comparative PK 
cohorts. There is no evidence of any remarkable effect of AUR101 on any clinical 
laboratory parameters, including hemoglobin, blood counts, liver function or kidney 
function or on ECG, vitals or physical examination. There were two cases of altered liver 
function parameters, one occurred in placebo treated subject (Grade 2) in MAD cohort 
and the other one in comparative PK part with open label AUR101 film coated tablet 
(Grade 1). Both of these events were deemed as related by the investigator, resolved and 
did not require any intervention. There were no Grade 3 or higher AEs or serious adverse 
events (SAEs) or any interruption or discontinuation of the study drug due to AE. 
 
Most commonly reported non-catheter associated Treatment-Emergent Adverse Events 
(TEAEs; reported ≥2 subjects receiving any dose of AUR101 or placebo) in SAD part 
were fatigue, headache, dizziness, nausea, vomiting, arthralgia, cough and backpain. In 
MAD part, most commonly reported non-catheter associated TEAEs were headache, 
abdominal pain, abdominal distension, abdominal discomfort, diarrhea and back pain. In 
comparative PK part, only headache was reported in ≥2 subjects. All of the AEs were 
mild to moderate in nature and resolved to the satisfaction of the PI.  There was no 
relevant difference between placebo and the AUR101 arms with respect to the nature, 
severity or frequency of AEs. There is also no pattern or relationship of AEs with 
AUR101 dose, schedule or formulation.  
 
The study findings from SAD cohorts also confirm that AUR101 is primarily absorbed in 
the stomach and minimal from intestine.  Moreover, food increases the exposure by ~2.5 
times, further re-confirming that retention of AUR101 in stomach leads to increased 
absorption.  
 
The MAD cohorts done with AUR101/placebo suspension in fed condition (with 
standard meal) showed Tmax of 4-5 hours with mean terminal elimination half-life 
ranging from 14 to 22 hours. Based on Cmax, AUC0-24 and AUC0-12, minimal increase in 
exposures was observed between 500 mg versus 1000 mg, suggesting that with a single 
time dose, peak in absorption likely occurs somewhere between 500 mg and 1000 mg. 
With BID dosing (600 mg BID), the Cmax and AUC0-12 substantially increased, when 
compared to both 500 mg and 1000 mg QD once daily regimens (Table 2). This is likely 


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because with increase in frequency of dosing (such as from QD to BID), AUR101 drug 
substance got two opportunities to be absorbed from the stomach, over 24-hour period, 
when an absorption kinetics plateau between 500 mg and 1000 mg with a single time 
dosing. 
 
Table 2: Key PK parameters from MAD cohorts  
 
Parameter 
 
Statistics 
500 mg QD x14 days 
(N=6) 
1000 mg QD x14 days 
(N=6) 
600 mg BID x14 days  
(N=6) 
 
  
Day 1 
Day 14 
Day 1 
Day 14 
Day 1 
Day 14 
Cmax (ng/mL) 
Mean (SD) 
3711.95 
(914.71) 
4480.74 
(877.35) 
4394.89 
(765.09) 
5052.64 
(1239.83) 
3597.27 
(1041.71) 
7837.99 
(2945.57) 
Geometric 
Mean 
(95% CI) 
3614.32 
(2763.07, 
4727.82) 
4412.66 
(3615.22, 
5385.99) 
4338.06 
(3597.84, 
5230.57) 
4899.70 
(3629.81, 
6613.86) 
3469.26 
(2538.19, 
4741.87) 
7462.85 
(5287.23, 
1.05E+04) 
 
Tmax (h) 
Mean (SD) 
3.67 (0.52) 
4.33 (0.82) 
4.67 (0.52) 
4.17 (0.98) 
3.67 (0.82) 
4.83 (0.41) 
Geometric 
Mean 
(95% CI) 
3.63 (3.11, 
4.25) 
4.26 (3.44, 
5.28) 
4.64 (4.11, 
5.24) 
4.06 (3.12, 
5.28) 
3.60 (2.87, 
4.50) 
4.82 (4.38, 
5.30) 
AUClast 
(h*ng/mL) 
Mean (SD) 
- 
103718.11 
(41883.94) 
- 
113826.95 
(41124.24) 
- 
193019.87 
(134249.01) 
Geometric 
Mean 
(95% CI) 
- 
96480.30 
(6.19E+04, 
1.50E+05) 
- 
107604.42 
(7.29E+04, 
1.59E+05) 
- 
168381.87 
(9.81E+04, 
2.89E+05) 
 
AUC0-12 
(h*ng/mL) 
Mean (SD) 
26977.52 
(8038.07) 
39513.84 
(10193.30) 
31584.64 
(5962.66) 
40487.02 
(10377.74) 
26713.79 
(8654.54) 
71386.18 
(30233.01) 
Geometric 
Mean 
(95% CI) 
25928.42 
(1.87E+04, 
3.60E+04) 
38508.93 
(2.98E+04, 
4.97E+04) 
31054.65 
(2.50E+04, 
3.86E+04) 
39111.81 
(2.84E+04, 
5.39E+04) 
25557.68 
(1.81E+04, 
3.60E+04) 
67485.43 
(4.72E+04, 
9.65E+04) 
AUC0-24 
(h*ng/mL)  
Mean (SD) 
41323.55 
(13348.11) 
64369.19 
(19024.52) 
49727.38 
(10147.46) 
65710.45 
(20131.72) 
- 
115400.32 
(57173.33) 
Geometric 
Mean 
(95% CI) 
39527.50 
(2.80E+04, 
5.58E+04) 
62152.73 
(4.60E+04, 
8.40E+04) 
48780.80 
(3.87E+04, 
6.15E+04) 
62758.16 
(4.35E+04, 
9.05E+04) 
- 
107285.97 
(7.18E+04, 
1.60E+05) 
AUC0-∞ 
(h*ng/mL) 
Mean (SD) 
- 
104487.16 
(42591.29) 
- 
116118.57 
(41138.27) 
- 
196048.96 
(139777.93) 
Geometric 
Mean 
(95% CI) 
- 
97050.25 
(6.19E+04, 
1.52E+05) 
- 
110101.95 
(7.55E+04, 
1.61E+05) 
- 
169987.05 
(9.79E+04, 
2.95E+05) 
 
t1/2 (h)  
Mean (SD) 
- 
14.98 (3.99) 
- 
22.43 (7.44) 
- 
16.18 (4.66) 
Geometric 
Mean 
(95% CI) 
- 
14.48 
(10.63, 
19.72) 
- 
21.37 
(14.85, 
30.76) 
- 
15.67 (11.77, 
20.85) 
SD = Standard Deviation; CI = Confidence Intervals; QD = once a day; BID = twice a day; Cmax = Maximum Concentration; 
Tmax = Time to reach Cmax; AUC = Area Under the Curve; t1/2 = Terminal elimination half-life;  
 
The Comparative PK part showed near identical exposures with AUR101 film-coated 
tablet and AUR101 suspension, confirming that the new film-coated formulation could 
be utilized in future clinical development and will provide same results as AUR101 
suspension, utilized in MAD cohorts (Table 3 and Figure 2). 
 
 


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Table 3: Key PK parameters from Comparative PK Cohort  
 
Parameter 
Statistic 
Treatment Group (600 mg AUR101) 
AUR101 suspension 
(period 1) 
AUR101 film coated tablet 
(period 2) 
(N=6) 
(N=6) 
Cmax (ng/mL)  
Mean (SD) 
3585.92 (696.12) 
3542.55 (1140.98) 
Geometric Mean 
(95% CI) 
3530.27 (2880.29, 4326.93) 
3377.50 (2347.05, 4860.36) 
 
Tmax (h) 
Mean (SD) 
4.50 (0.84) 
4.68 (1.23) 
Geometric Mean 
(95% CI) 
4.44 (3.71, 5.32) 
4.54 (3.40, 6.05) 
AUClast 
(h*ng/mL) 
Mean (SD) 
71114.81 (12818.65) 
70901.59 (19544.84) 
Geometric Mean 
(95% CI) 
70182.00 (5.83E+04, 8.45E+04) 
68948.03 (5.30E+04, 
8.98E+04) 
 
AUC0-12 
(h*ng/mL) 
Mean (SD) 
26581.99 (4979.52) 
26024.40 (6722.43) 
Geometric Mean 
(95% CI) 
26218.91 (2.17E+04, 3.16E+04) 
25284.64 (1.91E+04, 
3.34E+04) 
AUC0-24 
(h*ng/mL) 
Mean (SD) 
42879.12 (5053.75) 
43561.44 (10512.65) 
Geometric Mean 
(95% CI) 
42648.90 (3.79E+04, 4.80E+04) 
42511.01 (3.30E+04, 
5.48E+04) 
 
AUC0-48 
(h*ng/mL) 
Mean (SD) 
59675.79 (6429.20) 
60835.15 (14969.02) 
Geometric Mean 
(95% CI) 
59388.29 (5.30E+04, 6.65E+04) 
59418.11 (4.65E+04, 
7.60E+04) 
AUC0-∞ 
(h*ng/mL) 
 
Mean (SD) 
71686.12 (13439.29) 
71390.11 (20010.01) 
Geometric Mean 
(95% CI) 
70675.66 (5.83E+04, 8.57E+04) 
69368.84 (5.31E+04, 
9.06E+04) 
 
t1/2 (h) 
Mean (SD) 
14.74 (3.40) 
15.14 (4.03) 
Geometric Mean 
(95% CI) 
14.39 (11.12, 18.61) 
14.61 (10.62, 20.10) 
SD = Standard Deviation; CI = Confidence Intervals; Cmax = Maximum Concentration; Tmax = Time to reach Cmax; AUC = Area 
Under the Curve; t1/2 = Terminal elimination half-life;  


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Figure 2: Plasma concentration profile of AUR101 suspension (Period 1) vs. 
AUR101 film coated tablet (Period 2) in Comparative PK part  
 
Error bars represents standard errors of mean. 
 
With respect to PD biomarker evaluation, IL-17 inhibition correlated well with 
exposures in the Phase 1 study .Better, sustained and consistent IL-17 inhibition (≥ ~80%  
IL-17 inhibition throughout the day) was observed with BID dosing as compared QD 
dosing (Figure 3), and forms the basis for the dosing regimen for future clinical studies.  
Figure 3: Mean IL-17 secretion in MAD cohorts  
 
C1- Cohort 1, C2- Cohort 2, C3- Cohort 3. Error bars represents standard errors of mean.  
3.4 Rationale for Current Study 
AUR101 is a potent and selective inhibitor of RORγ with good cellular activity in 
Th17 differentiation assays. The compound has also demonstrated good efficacy in 
relevant in vivo models. Toxicology studies with the compound have also 
100
100
100
100
20.3
26.6
14.1
127.8
31.5
20.8
106.3
36
24.2
20.6
107.1
0
20
40
60
80
100
120
140
160
C1 (500 mg QD x 14 days)
C2 (1000 mg QD x 14 days)
C3 (600 mg BID x 14 days) Pooled Placebo (QD or BID x
14 days)
Mean Residual IL-17 secretion, 
percent change from pre-dsoe 
Pre-dose
6-hours
12-hours
24-hours


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demonstrated a favorable safety profile at the exposures showing efficacy in animal 
models. The FIH study has determined a desirable safety, PK and optimal IL-17 
inhibition, when AUR101 is administered up to 600 mg PO BID.  
In view of favorable preclinical safety, preclinical efficacy, and PK, PD and safety 
data derived from FIH study, there is a strong scientific rationale for continued clinical 
development of AUR101. The Phase II development plan will initially evaluate 
efficacy and safety of AUR101 in patients with moderate to severe psoriasis at 600 mg 
PO BID as well as 400 mg PO BID, with both dosages administered for 12 weeks and 
compared with matching placebo in a double blind, double dummy study (AUR101-
201; Current Study). In future, additional Phase II studies in other autoimmune 
diseases, such as atopic dermatitis, and non-infectious auto-immune uveitis, either as 
single agent or in combination with standard of care, may be done. 
3.4.1 Basis for Dose Selection  
Repeat dose toxicology studies in rats and dogs for 13-weeks showed NOAEL doses 
of 450 mg/kg/day and 60 mg/kg/day (30 mg/kg BID) respectively. At higher doses in 
dogs (60→50→40 mg/kg BID), treatment related adverse findings were observed 
including severe clinical signs, body weight losses, low food consumptions, and 
increased ALT and AST. So, dog is considered more relevant and sensitive species.  
The dosage and dosing schedule (BID) in the current Phase II study (AUR101-201) in 
patients with moderate to severe psoriasis is determined from the level and 
consistency of IL-17 modulation in the Phase I study (AUR101-101) (See Section 
3.3) at different MAD cohorts. Specifically, in MAD Cohort 3 (600 mg PO BID x 14 
days), the mean IL-17 level on Day 15 was ~ 80% below baseline value (Figure 3). 
This dose is, therefore, chosen as one of the two dosages in the proposed (AUR101-
201) Phase II study. A lower dose (400 mg PO BID) is also proposed as investigating 
two separate dosages in Phase II will provide the risk-benefit analysis for two separate 
dosages and will help decide the dosage for Phase III. 
The Day 14 human exposures,  at 600 mg PO BID, is also compared with the NOAEL 
exposures, on Day 91 from the 13-week toxicology study in dogs. This comparison 
provides a 2.5-fold safety window (for 600 mg PO BID dose) and thus considered 
acceptable from safety perspective.  
 
 


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Table 4: Summary of Safety margin calculation based on NOAEL exposure in 
animals and MAD exposure in humans 
Study 
Findings 
Mean Exposure (AUC0-
24h) at NOAEL on the last 
day of dosing or Day 14 in 
MAD cohort 3 (hr*ng/mL) 
Safety margin in 
humans with 
respect to 
NOAEL 
exposure
13-week oral rat 
toxicity study 
NOAEL 450 
mg/kg/day 
473472 
 
3.3 
13-week oral dog 
toxicity study 
NOAEL 60 
mg/kg/day 
364160 
2.5 
MAD cohort 3 for 
14 days 
Dose 600 mg 
BID 
142764# 
- 
HED = Human Equivalent Dose; NOAEL = No-Observed-Adverse-Effect Level. BID-= twice a day, 
MAD = Multiple Ascending Dose 
#Mean AUC0-12 on Day 14 was 71386.18 hr*ng/mL. Hence, AUC0-24 is calculated as 2xAUC0-12  
 
3.4.2 Basis for Placebo controlled study 
Psoriasis is a chronic immune-mediated disorder, characterized by relapses and 
remission. The disease persists throughout the life, and may manifest at unpredictable 
intervals. Spontaneous remissions may also occur. Moreover, presentation of the 
disease is influenced by various environmental (e.g. weather), genetic and 
psychosocial factors [14].  Since the disease is not life-threatening and there are 
possibilities of natural improvement of the disease, only a placebo-controlled study 
can reliably provide proof of effect in this scenario. ICH guidelines confirm this 
rationale [15]. Consistent with ICH guidelines and regulatory recommendations [16], 
several drugs (apremilast, secukinumab, ustekinumab etanercept, adalimumab etc.) 
have been evaluated in psoriasis in placebo-controlled Phase II and Phase III studies, 
with similar eligibility criteria and duration as the current study. Not surprisingly, in 
almost all these studies, 75% reduction from baseline PASI score (i.e. PASI75) was 
achieved in 4-10% of the placebo population, confirming the necessity of a placebo-
control in this disease [17-24].  
In addition to efficacy, placebo-controlled study will provide maximum ability to 
distinguish adverse effects caused by a drug from those resulting from underlying 
disease or intercurrent illness (i.e. by chance). 
With this background, it is important to perform placebo-controlled study with 
AUR101 in moderate to severe psoriasis patients to get objective evidence of safety 
and efficacy. 


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In addition, frequent study visits as well as rescue therapies are allowed by the 
protocol to ensure adequate safety of the patients during the study period.   
4.0 OBJECTIVES  
4.1 Primary Objective 
 To assess efficacy of AUR101 in patients with moderate-to-severe psoriasis  
4.2 Secondary Objectives 
 
To evaluate the safety and tolerability of two oral doses of AUR101 in patients 
with moderate-to-severe psoriasis  
 
To evaluate the plasma pharmacokinetics of AUR101 in patients with 
moderate-to-severe psoriasis  
 
To evaluate effect of AUR101 on quality of life in patients with moderate-to-
severe psoriasis. 
5.0 ENDPOINTS 
5.1 Primary Endpoint 
1. 
Proportion of patients achieving PASI 75 (i.e. 75% reduction from baseline 
PASI score) at the end of week 12.  
5.2 Secondary Endpoint 
1. 
Proportion of patients achieving PASI 75 (i.e. 75% reduction from baseline 
PASI score) at the end of week 4 and 8.  
2. 
Proportion of patients achieving PASI 50 (i.e. 50% reduction from baseline 
PASI score) at week 4, 8 and 12.  
3. 
Proportion of patients achieving IGA 0 or 1 at week 4, 8 and 12. 
4. 
Percent change from baseline in PASI score at week 4, 8 and 12 
5. 
Change from baseline in IGA scale at week 4, 8 and 12 
6. 
Change from baseline to week 4, 8 and 12 in percent Body Surface Area (BSA) 
involved 
7. 
Change from baseline to week 4, 8 and 12 in Dermatology Life Quality Index 
(DLQI) 
Safety and tolerability Assessment 
1. Safety will be evaluated based on the nature and incidence of treatment 
emergent adverse events (AEs), vital signs, electrocardiograms (ECGs), 
laboratory assessments and physical examinations in patients treated 
with AUR101 or placebo  
6.0 
STUDY DESIGN 


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6.1 
Overview 
This will be a multicenter, double-blind, double-dummy, placebo controlled, 
randomized study to evaluate efficacy and safety of two doses of AUR101 in patients 
with moderate-to-severe psoriasis  
There will be three arms – two arms of AUR101 (400 and 600 mg BID) and one arm 
of placebo.  
All the patients will be followed up for 14 ± 2 days of their last dose for safety 
assessment. 
A subset of approximately 25 consenting patients will participate in the 
pharmacokinetic part in addition to main study. Separate consent will be taken. If 
patient consents for PK, samples will be collected at week 4 (±2 days) visit of dosing.  
6.2 
Number of Patients and Duration of Treatment 
Approximately 90 patients with chronic moderate-to-severe plaque psoriasis will be 
randomized to each of the three arms (1:1:1 randomization). All the patients will 
receive study drugs for 12 weeks in a double blind, double dummy fashion. 
6.3 
Formulation and Mode of Administration 
AUR101 will be formulated as 100 and 300 mg film coated tablets. Patients will take 
study drugs orally with water, twice daily after meals (breakfast and dinner), 
preferably same time each day.  
6.4 
Schedule of Visits and Assessments 
See Table 1 for the Schedule of Events. 
6.4.1 Screening Visit (Up to Day -14) 
All Screening assessments will occur within 14 days prior to administration of the 
first dose of study drug 
Informed consent must be obtained at this visit before study procedures are 
performed. Further details regarding informed consent are provided in Section 13.3. 
A screening log will be kept to record patients who sign the informed consent form 
and who will be screened. For those patients who will be screen failures, a reason 
will be documented.  
Rescreening of subjects who have been declared screen failure is not advocated. If 
rescreening of any patient is required, site staff should discuss with sponsor medical 
monitor.  
The following assessments/information will be performed/ recorded: 
 Obtain patient demographics, medical history, previous anti-psoriasis therapies 


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and prior/concomitant medication data (medications taken up to 4 weeks prior 
to screening 
 Conduct complete physical exam, 12-lead ECG, and vital sign (temperature, pulse 
rate, blood pressure) assessments, including weight and height. 
 Menstrual history in females  
 Check inclusion/exclusion criteria  
 Clinical laboratory tests (blood sample for hematology and biochemistry tests) 
including QuantiFERON TB-Gold test 
 Viral serology for hepatitis B (HBsAg), hepatitis C (Anti-HCV Ab), HIV I and II 
antibody test  
 Perform area and severity assessment of psoriasis. Independent dermatologist 
should perform PASI, involved BSA and IGA assessment in addition to Principal 
Investigator (PI) or Co-Investigator (Co-I).  
 Perform serum pregnancy test for females of childbearing potential.  
6.4.2 Visit 2: Randomization Visit (Day 1) 
Those patients who are eligible for the study, based on the inclusion and exclusion 
criteria, will be invited for the next visit. At this visit, randomization will be 
performed by Integrated Web based Randomization System (IWRS).  
The following assessment/information will be performed /recorded.   
 
Verification of inclusion/exclusion criteria 
 
Conduct physical exam and vital sign (temperature, pulse rate, blood pressure) 
assessments, including weight. 
 
Check medical history  
 
Check prior and concomitant medications  
 
AEs (illnesses that started between informed consent and the first dosing occasion 
will be recorded in AE page but will be considered as non-treatment emergent 
AE) assessment 
 
Independent dermatologist should perform PASI and involved BSA evaluation in 
addition to Principal Investigator (PI) or Co-Investigator (Co-I).  
 
Investigator should mark 1-2 major psoriasis lesions (Index lesions) for taking 
photographs. The lesions should be representative of overall severity, easily 
accessible and re-evaluable at subsequent study visits 
 
DLQI questionnaire should be explained to the patient and needs to be filled by 
the patient.  
 
Urine pregnancy test for females of childbearing potential only (Beta-hCG) 
 
Perform clinical laboratory tests as per Section 9.2.3.  


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 
Dispense study drug as directed by IWRS 
6.4.3 Treatment Visits (Visits 3-7) 
On treatment, patients will be asked to come at Week 2 (±2 days), Week 4 (±2 
days), Week 6 (±2 days), Week 8 (±2 days) and Week 12 (±4 days).  
The following assessments/information will be performed/ recorded at respective 
visit according to Table 1: (see Section 9.0 for more details): 
 
Conduct physical exam and vital sign (temperature, pulse rate, blood pressure) 
assessments at every visit, and weight at visit 4 and 6, 7.   
 
Check medical history at every visit.   
 
Check prior and concomitant medications at every visit.   
 
Independent dermatologist should perform PASI, involved BSA and IGA 
evaluation in addition to Principal Investigator (PI) or Co-Investigator (Co-I) at 
every visit.   
 
DLQI questionnaire should be filled by the patient at every visit.    
 
Photographs of the designated lesions should be taken at every visit.   
 
Perform clinical laboratory tests as per Section 9.2.3 at Week 4, 8 and 12 visits 
only.  
 
AE assessment at every visit 
 
Dispense study drug as directed by IWRS except visit 7.  
 
Count unused study drugs and evaluate compliance at every visit.    
 
Perform urine pregnancy tests at Week 4, 8 and 12 visits only. 
 
Perform PK sampling at Week 4 visit in consenting patients. These patients will 
be advised to come to the site without taking study drug for the respective visit. 
Study drug will be given at the site (after breakfast), followed by PK sampling.  
6.4.4 Follow up visit (Visit 8) 
Patients will return to the site 14 ± 2 days after their last dose for a follow up visit.    
The following assessment/information will be performed/ recorded: 
 Conduct physical exam, 12-lead ECG, and vital sign (temperature, pulse rate, 
blood pressure) assessments. 
 Check medical history  


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 Check prior and concomitant medications 
 Independent dermatologist should perform PASI and BSA evaluation in addition 
to Principal Investigator (PI) or Co-Investigator (Co-I) 
 DLQI questionnaire should be filled by the patient  
 Photographs of the designated lesions should be taken.  
 AE assessment 
 Clinical laboratory tests for follow up visit (as mentioned in Table 6)  
 Urine pregnancy test for females of childbearing potential only (Beta-HCG) 
For patients who are withdrawn from the study for any reason, withdrawal procedures 
as defined in Section 7.4 will be followed. 
7.0 STUDY ENROLLMENT AND WITHDRAWAL 
7.1 
Inclusion Criteria 
1. Confirmed diagnosis of chronic plaque-type psoriasis, diagnosed at least 6 
months before screening 
2. Psoriasis of at least moderate severity, defined as PASI≥12 and involved BSA≥10 
% at screening and Day 1  
3. Adult males or females, ≥ 18 to ≤ 65 years of age,  
4. Ability to communicate well with the investigator and to comply with the 
requirements of the entire study  
5. Willingness to give written informed consent (prior to any study related 
procedures being performed) and ability to adhere to the study restrictions and 
assessments schedule. 
7.2 
Exclusion Criteria  
1. History of erythrodermic, guttate, or pustular psoriasis within last 12 months 
2. Efficacy failure on any biologic (e.g. IL-17 antibodies like brodalumab or 
ixekizumab or anti-TNF agents. like etanercept, infliximab or adalimumab) for 
the treatment of psoriasis  
Note: Efficacy failure is defined as: A) Failure to achieve static 
Physician/Investigator Global Assessment (PGA/IGA) of 0 to 2 (i.e. clear to 
mild) despite a continuous treatment with biologic at the approved (as in 
package insert) dose for at least 8 weeks B) After having an efficacious 
response, PGA/IGA increased to 3 or higher while receiving the approved (as in 
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3. Static 5-point IGA mod 2011 scale of 0 to 2 at screening or Day 1. 
4. BMI ≥ 35 kg/m2 
5. Current treatment or history of treatment for psoriasis with IL-17 or IL-12/23 
antagonist biological agents (e.g. secukinumab, briakinumab, tildrakizumab, 
ustekinumab etc.) within 6 months prior to study day 1 
6. Current treatment or history of treatment for psoriasis with other biological 
agents (e.g. adalimumab, etanercept, infliximab, alefacept etc.) within 3 months 
prior to study day 1  
7. Current treatment or history of treatment for psoriasis with non-biological 
systemic medications (including systemic steroids, methotrexate, cyclosporine 
etc.) or phototherapy within 4 weeks prior to study day 1.  
8. Treatment with medicated topical agents (having active pharmaceutical 
ingredient that can impact the interfere with effect of the study drug; See section 
8.11) within 2 weeks prior to study day 1 
9. History or presence of any medical or psychiatric disease, or clinically 
significant laboratory / ECG abnormalities at screening, any or a combination of 
illnesses, which, in the opinion of the PI, may either put the patient at risk 
because of participation in the study, or influence the results or the patient's 
ability to participate in the study.  
10. Evidence of organ dysfunction (e.g. liver dysfunction ≥ 1.5 X of ULN for ALT, 
AST or ALP or Total Bilirubin, or renal dysfunction of 1.5X of ULN of serum 
creatinine)  
11. Any surgery requiring general anesthesia within 3 months prior to screening 
12. Known or suspected history of alcoholism or drug abuse, as judged by the 
investigator  
13. History or presence of malignancy except patients with non-melanoma skin 
cancer or carcinoma in situ of cervix who are allowed to participate in the study  
14. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface 
antigen (HBsAg), or hepatitis C antibodies (HCV Ab) at screening 
15. Patient with known past history of systemic tuberculosis or currently suspected 
or known to have tuberculosis 
16. Patient expected to be started on anti-tubercular therapy either for treatment or 
prophylaxis of tuberculosis 
17. Suspected tuberculosis infection as evident from a positive QuantiFERON TB-
Gold test (QFT) at screening. Patients with a positive QFT test may participate 
in the study if further work up as per the opinion of the investigator (like Chest 


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X-ray or CT scan of chest or other locally acceptable method for diagnosing 
active tuberculosis) establishes that patient does not have active tuberculosis.  
18. History of hypersensitivity or idiosyncratic reaction to any investigational ROR-
gamma inhibitors or any of the excipients of study drug 
19. Any previous gastrointestinal surgery or recent (within 3 months) / current 
history of gastrointestinal disease, that in the opinion of investigator, could 
impact the absorption of the study drug 
20. Positive pregnancy test for women of child bearing potential (WOCBP) at the 
screening or randomization visit 
21. Male patients with partners of childbearing potential not willing to use reliable 
contraception methods. 
22. Pregnant or lactating women or WOCBP who are neither surgically sterilized 
nor willing to use reliable contraceptive methods (hormonal contraceptive, IUD 
or any double combination of male or female condom, spermicidal gel, 
diaphragm, sponge, cervical cap) 
23. Has received another new chemical entity/investigational drug within 28 days or 
5 half-lives of investigational drug (whichever is longer) of the first 
administration of investigational product in this study prior to study day 1.   
24. Use of herbal remedies, mega dose vitamins (intake of 20 to 600 times the 
recommended daily dose) and minerals during the 2 weeks prior to the first 
administration of investigational product. 
25. Patients who have received live or attenuated vaccine in the 4 weeks prior to 
study day 1. 
7.3 
Withdrawal of Patients from Study Treatment 
Patients may decide to withdraw from the study at any time without prejudice to any 
benefits. Although a patient is not obliged to give his reason(s) for withdrawing 
prematurely from the trial, the investigator should make a reasonable effort to 
ascertain the reason(s) while fully respecting the patient’s rights. 
The investigator may withdraw a patient for any of the following reasons: 
 
Intolerable adverse event  
 
If patient’s condition is deteriorating, continued participation of the patient 
would be an unnecessary risk to the patient’s health, in the opinion of the 
investigator 
 
Use of rescue medication 
 
PASI increases by 50% from baseline, after 6 weeks of trial participation (from 
Day 1) 
 
Non-compliance 
 
Major protocol deviation/violation 
 
Lost to follow-up 


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 
Study blind is broken 
 
Termination of the study by the Sponsor. 
 
Sponsor’s request 
 
Other as per investigator’s discretion 
7.4 
Withdrawal Procedures 
If a patient is withdrawn from the study, the primary reason for withdrawal must be 
recorded in the eCRF. If a patient is withdrawn during the study period after dosing, 
all safety assessments (e.g. AEs, vitals, ECG, laboratory assessments etc.) according 
to “End of Treatment” (Week 12±4 days) visit should be performed. Patient will be 
asked to come 14±2 days after last dose for follow up visit assessments according to 
study activities Table 1 If a patient is withdrawn before study drug administration, 
then safety assessments is not required.  
The last date of study drug administration must be documented. 
Appropriate follow-up of all withdrawn patients will be performed, as required. If a 
withdrawn patient does not follow up, then adequate attempts to contact the 
withdrawn patient must be documented before declaring a patient ‘Lost to Follow 
up’. 
7.5 
Replacement of Withdrawals 
If a patient is withdrawn after randomization without any safety or lack of efficacy 
issues, then he/she may be replaced after consultation with sponsor.  
7.6 
Early Study Termination 
The Sponsor has the right to close the study at any time, although this should occur 
only after mutual consultation between the Sponsor and the Investigators. Events 
that may trigger early study termination include but are not limited to: 
 Change in development plans for the study drug 
 Slow recruitment. 
8.0 INVESTIGATIONAL PRODUCT 
8.1 Description: 
 
AUR101 film coated tablet 
Laboratory Code 
AUR101  
Excipients 
Microcrystalline cellulose, lactose monohydrate, 
Croscarmellose sodium, Hypromellose, Sodium 
lauryl Sulphate, Sodium Stearyl Fumarate and 
coating excipients (Opadry II white) 
Formulation 
Film Coated Tablet  
Strengths 
100 and 300 mg strengths  
Route of 
Oral 


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Placebo for film coated tablet 
Excipients 
Microcrystalline 
cellulose, 
lactose 
monohydrate, 
Croscarmellose sodium, Hypromellose, Sodium lauryl 
Sulphate, Sodium Stearyl Fumarate and coating 
excipients (Hypromellose, Talc and Acryl-Eze coating 
powder 
Formulation 
Film Coated Tablet 
Strengths 
Placebo according to 100 and 300 mg strengths of 
AUR101 
Route of 
administration 
Oral 
Placebo tablet will have an identical appearance corresponding to the strength of 
AUR101 film coated tablet. 
8.2 
Supply and Storage 
The investigational products will be manufactured, handled and stored in 
accordance with Good Manufacturing Practice (GMP) and used in accordance with 
this protocol. Aurigene Discovery Technologies Ltd. (sponsor) will ensure the 
supply of investigational products and will also ensure that the drug supplies are 
suitable for human use. 
The packaging supplied by the sponsor will be labelled as per local regulations. 
On receipt of the study drugs at site, site staff will check the number of bottles and 
complete documentation of receipt.  
The study drugs will be kept in a secure, temperature controlled, restricted access 
location and in accordance with applicable regulatory requirements. AUR101 and 
placebo tablets should be stored at a temperature of 2-8°C & in original package in 
order to protect from light and temperature logs will be maintained. Patients will be 
advised to store the study drug in refrigerator. 
The investigator will ensure that the investigational products are used only in 
accordance with this protocol. 
8.3 
 Blinding 
 This will be a double-blind, double-dummy study. As shape of 100 and 300 mg of 
AUR101 tablets are different, double-dummy design is adopted to ensure the 
blinding. 
Each patient will receive one of the following combinations:  
 
 
administration 


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Table 5: Study drug administration according to treatment arms 
So, every patient will receive one tablet of 100 mg active/placebo and 2 tablets of 300 
mg of active/placebo as morning and evening dose. To reiterate, every patient will 
receive 3 tablets in the morning and 3 tablets in the evening.  
8.4 
Randomization 
8.4.1 
 Preparation of randomization code 
The randomization list will be generated by an Independent Statistician who will 
remain unblinded and will not be involved in the conduct of the study. The 
randomization list will be maintained as a password protected file and it will be 
shared to unblinded personnel of depot for preparation of individual kits for the 
patients. All randomization information will be secured and kept in a locked storage 
area, accessible only by authorized personnel.  
8.4.2 
Randomization of patients 
Only patients who meet all the inclusion criteria and none of the exclusion criteria are 
eligible for randomization.  
Randomization will take place on Visit 2. Each patient will be given a randomization 
number by IWRS. System will allocate the kit according to randomization number. 
Site staff will dispense the study kit accordingly.   
8.4.3 
Breaking the randomization code 
There is no known antidote of AUR101 and in general a knowledge that a patient is 
on active drug or placebo will not help in the management of AEs or SAEs, and thus 
unblinding is discouraged. Still, if the PI believes that knowledge of randomization 
code may help in managing the patient in the face of an AE or SAE, then the same 
would be made available to the PI. In such a situation, the respective EC will also be 
notified if the code is broken during the study. The date, time and reason and the 
Dose 
timing 
Morning dose 
Evening dose 
Arms 
100 mg 
active/ 
placebo 
300 mg 
active/ 
placebo 
300 mg 
active/ 
placebo 
100 mg 
active/ 
placebo 
300 mg 
active/ 
placebo 
300 mg 
active/ 
placebo 
400 mg 
BID 
100 mg 
active 
300 mg 
active 
300 mg 
placebo 
100 mg 
active 
300 mg 
active 
300 mg 
placebo 
600 mg 
BID 
100 mg 
placebo 
300 mg 
active 
300 mg 
active 
100 mg 
placebo 
300 mg 
active 
300 mg 
active 
Placebo 
BID 
100 mg 
placebo 
300 mg 
placebo 
300 mg 
placebo 
100 mg 
placebo 
300 mg 
placebo 
300 mg 
placebo 


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name of the person who opened the code will be recorded. If the blind is broken, the 
patient must be withdrawn from the study.  
8.5 
Dispensing 
Site staff will dispense the bottles according to IWRS direction. A dispensing log 
and accountability log will be maintained. 
8.6 
Method of Administration 
AUR101 or matching placebo tablets will be supplied in bottles. The patients will be 
asked to swallow the tablets as whole with water, immediately after food in the 
morning and evening. It is necessary for the patient to take the study drug only after 
food (breakfast and dinner, respectively).   
8.7 
Compliance 
As mentioned in Table 1, visit 3 onwards till end of treatment visits, study staff will 
count the unused tablets in the bottles and will assess the compliance of the patient.  
Patients should also be advised to keep these tablets out of reach from children  and 
also not to take the drug only as directed by the investigator. 
8.8 
Accountability 
The study staff will be responsible for drug accountability. Records will be kept for: 
 
All study drugs delivered to the trial site 
 
All study drugs dispensed 
 
The administration to each patient 
 
All study drugs returned by the patients 
 
All study drugs remaining are returned to depot/destroyed. 
These records will include dates, quantities, batch numbers, expiry dates, and the 
unique code numbers assigned to the investigational products and trial patients. 
The sponsor or its designee will monitor the drug accountability records during the 
study and will perform drug reconciliation at the end of the study. 
At the end of the study, unused study drugs will be returned to the pharmacy 
depot (designated by the sponsor) or destroyed, as directed by the sponsor (by 
written authorization). The return/destruction of all investigational medicinal 
products will be documented appropriately. 
8.9 
Treatment of Overdose 
Based on the preclinical data and Phase I clinical data, the study drug is expected to 


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be well tolerated at currently recommended dosages. Still in the unforeseen event of 
an overdose of study drug, the patient should be given supportive treatment 
depending on the symptoms, and gastric lavage may also be done. There are no 
known antidotes for AUR101 or any other RORγ inhibitor.  
8.10 Prior and Concomitant Medications  
Concomitant medications and treatments will be collected from Screening through the 
Follow up visit. All prior and concomitant anti-psoriasis therapy will be collected, 
including biologics, non-biologic systemic therapies, phototherapy and topical 
treatments. In addition, other concomitant medications used for any indication (e.g. 
diabetes mellitus, hypertension, etc.) apart from psoriasis will be collected for at least 
4 weeks prior to screening visit.  
The patient should be asked to notify the study site about any new treatments 
(including over-the-counter drugs, supplements, calcium, vitamins and herbal drugs) 
he/she takes after signing informed consent. All medications and significant non-drug 
therapies (including physical therapy, procedures) administered, must be recorded.  
No concomitant medication information will be collected following patient 
discontinuation from the study except for concomitant medication use associated with 
study drug-related adverse events or adverse events that lead to discontinuation from 
the study.  
8.11 Prohibited Concomitant Medications 
Use of any treatments that could confound the efficacy are not allowed during the 
study for any indication. Following drugs are not allowed during the study period:  
 Treatment with topical corticosteroid, topical vitamin D analogues, 
pimecrolimus, tacrolimus, retinoids, salicylic acid, lactic acid, tar, urea, α-
hydroxy or fruit acids 
 Treatment 
with 
systemic 
corticosteroids 
or 
non-steroidal 
systemic 
immunosuppressive 
or 
immunomodulator 
drugs 
(e.g., 
cyclosporine, 
methotrexate, mycophenolate-mofetil, azathioprine, etc.) or phototherapy 
 Treatment with any drug, including any biological immunomodulating agents 
like adalimumab, etanercept, secukinumab, ustekinumab etc. which can affect 
psoriasis 
If the investigator use of any of above treatments is required, then the patient should 
not be randomized into the study. Additionally, any live virus vaccination during the 
study is not permitted. 
If a patient receives any prohibited medication or live virus vaccination during the 
study period, he/she should be discontinued from the study by the investigator after 
consultation with sponsor medical monitor. Withdrawal procedures as mentioned in 
section 7.4 should be performed.  
Patients are also advised to avoid extreme long exposures to sunlight like sun-bathing 


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during the study period.  
If patient has received any of the above-mentioned therapy before randomization, 
adequate gap between initiation of study treatment and last dose of prohibited 
medication should be ensured as mentioned in exclusion criteria no. 5 to 8. 
Whenever in  doubt about confounding, investigators are recommended to discuss 
with sponsor medical monitor before starting any new drug during the study period.   
8.12 Permitted therapy for psoriasis 
Only bland emollients or shampoos (for scalp psoriasis) will be allowed during the 
study 
participation. 
It 
means 
that 
all topical 
medications 
that 
contain 
pharmacologically active ingredients will not be allowed during the study. Sponsor 
will provide bland topical preparations to maintain uniformity across the patients, as 
required.  
8.13 Rescue Medication 
If patient’s PASI score is increasing by at least 50% from baseline level at or after 6 
weeks of therapy, patient can be given rescue medication as considered appropriate 
according to investigator.   In other situations, if medically necessary (i.e. to control 
intolerable psoriasis symptoms), rescue treatment for psoriasis may be provided to 
study patients at the discretion of the investigator after discussion with sponsor 
medical monitor. In addition, even within first 6 weeks of therapy, if a patient has 
intolerable symptoms from psoriasis, then rescue medications can be administered. 
The investigator can choose any available medication, including any biologic 
medications, such as secukinumab or adalimumab, as rescue medication to treat 
psoriasis. The choice of rescue medication is not part of the study and should be 
decided by the PI on an individualized assessment of the patient. With respect to the 
decision to use rescue medication, investigator should discuss with the sponsor 
medical monitor.  
Considering the mechanism of action of study drug, it may take 4-6 weeks to show 
visible effects on the disease. Hence, investigators are advised to continue the study 
drug as long as possible unless the symptoms are intolerable and severely affect 
patient’s health condition.  
For the purpose of efficacy analysis, patients who receive rescue treatment during the 
study treatment period will be considered treatment failures. Investigators should 
make every attempt to conduct efficacy and safety assessments (e.g. disease severity 
scores, safety labs) immediately before administering any rescue treatment. An 
unscheduled visit may be used for this purpose if necessary. Patients who receive 
“Rescue Medication” will be discontinued from the trial. All such patients should be 
followed up after 14 ±2 days of study drug discontinuation for safety assessment. 
8.14 Contraception Methods  
Women of childbearing potential and men who partner with a woman of childbearing 
potential must agree to use contraceptive methods which, in the Investigator's opinion, 


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are highly effective and adequate for the patient's circumstances while on 
investigational agent and at least 28 days after last dose. A woman of childbearing 
potential is defined as a premenopausal female or woman <1 year after the onset of 
menopause who is considered capable of becoming pregnant.  
Highly effective methods of contraception for this study include:  
• 
Hormonal implanted contraceptive  
• 
Birth control pills (combined oral contraceptive)  
• 
Intrauterine device  
• 
Birth control patch  
• 
Hormonal injected contraceptive  
• 
Sterilization  
• 
Abstinence (if in line with the patient's usual and preferred lifestyle)  
• 
Double barrier method - Male condom with cervical cap/diaphragm, Male 
condom with vaginal spermicide or similar combination. 
8.15 Drug Interactions/Precautions 
AUR101 is metabolically stable molecule with low metabolism by CYP enzymes. It 
is neither a CYP  inducer or inhibitor in in-vitro studies. So, drug interaction potential 
of AUR101 is low for CYP-mediated drug-drug interaction. Furthermore, AUR101 is 
neither a substrate nor an inhibitor of P-glycoprotein (P-gp) and Breast Cancer 
Resistant Proteins (BCRP) transporters. 
9.0 
STUDY ASSESSMENTS 
This study is divided into 3 periods: Screening, Treatment, and Follow-up. The 
schedule of study procedures is presented in the Schedule of Events (Table 1). 
Window period for each visit is defined in the Table 1. All times should be recorded 
using the 24-hour clock (e.g., 23:20, not 11:20 PM). A description of individual study 
assessments is provided below. 
9.1 
Demographics and Medical History  
Demographics and medical history will be obtained by the Investigator or designee 
during the Screening Period. Demographics will include date of birth (or age), sex, 
ethnicity, and race. Relevant medical history should be recorded and should include 
prior/current medical conditions, including psoriasis diagnosis, and abnormal physical 
exam findings or clinically significant laboratory abnormalities (excluding study 
disease-related abnormalities) from the baseline assessment. 
9.2 
Safety and Tolerability Assessments 
9.2.1 Adverse Events 
Monitoring and recording of AEs will be conducted and recorded throughout the 
study, starting from signing the ICF. Treatment-related AEs/SAEs that are ongoing at 
the time of Follow-up visit should continue to be followed until resolution, return to 
baseline, or until the investigator considers that further follow-up is not necessary. 
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10.0.   
9.2.2 Physical Exam and Vital Signs 
A complete physical exam will be performed at every visit. Vital signs include 
temperature (oral or axillary), pulse rate and blood pressure (seated or supine for at 
least 5 minutes) assessed at every visit. One temperature method should be selected 
for each patient and used consistently at each assessment throughout the duration of 
study. 
Weight will be recorded at every visit except visit 3, 5 and follow up visit. Height will 
be captured at screening only.  
9.2.3 Clinical Laboratory Test 
A blood sample will be taken for measurement of hematology and biochemistry 
parameters, and a urine sample will be taken for urine analysis at the following time 
points: 
 
Screening visit  
 
Randomization visit (Visit 2) 
 
Week 4, 8 and 12 (Visits 4, 6 and 7) 
 
Follow-up visit 
In addition, viral serology tests will be performed at the screening visit. Following 
parameters (Table 6) will be measured:  
Table 6: List of Clinical Laboratory Tests  
 
 
Haematology 
Red blood cells 
White blood cells (WBCs) 
Differential WBC count (absolute 
and %) including neutrophils, 
eosinophils, basophils, monocytes, 
lymphocytes 
Haemoglobin 
Haematocrit 
Platelets 
Mean corpuscular haemoglobin 
MCH concentration 
Mean corpuscular volume 
     
 
Biochemistry 
Alkaline phosphatase 
ALT 
AST 
Potassium 
Serum Creatinine 
BUN  
Sodium 
Chloride 
Bicarbonate 
Phosphorus 
Calcium 
Total bilirubin 
Albumin 
Globulin 
Total Protein  
Albumin/Globulin ratio 
Glucose 
Urinalysis (on Visit 2 and visit 7 only) 
Routine & microscopic examination 
Viral serology (For screening only) 
HBsAg, hepatitis C antibody, HIV I, HIV II 


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9.2.4 Electrocardiogram  
Standard, single 12-lead ECGs at Screening and Follow-up visits will be performed. 
Heart rate and PR, QRS, QT, and QTc (Bazett) intervals will be entered in eCRF. 
During Screening, if the ECG reading shows any abnormality, it must be repeated two 
more times to confirm the findings, and then the patient should be assessed if (s)he 
should be ineligible for the study.  
Machine read normal ECGs are acceptable for the study. ECGs read as abnormal by 
machine must be read by the PI / local ECG reader for final results. 
9.3 
Efficacy Evaluations 
9.3.1 
Psoriasis Area and Severity Index (PASI) 
PASI is widely used tool to measure the severity of psoriasis. It combines area of the 
lesions with severity of individual lesions by grading erythema, induration/thickness 
and scaling. It can be 0 (minimum) to 72 (maximum). 
For this study, an independent dermatologist at each site will evaluate PASI score at 
every visit for patients of the respective site. Additionally, PI will also evaluate PASI 
score independently.  
A PASI score [25-27] will be derived as indicated in Table 7. The head, trunk, upper 
limbs and lower limbs are assessed separately for erythema, thickening (plaque 
elevation, induration), and scaling (desquamation). The average degree of severity of 
each sign in each of the four body regions is assigned a score of 0-4. The area covered 
by lesions on each body region is estimated as a percentage of the total area of that 
particular body region.  
Table 7: PASI Score 
Body part 
Erythema (E) 
Thickening 
(plaque 
elevation, 
induration, I) 
Scaling 
(desquamation, 
D) 
Area score 
(based on true 
area %)# 
Head (H) 
including neck 
0=none  
1=slight  
2=moderate  
3=severe  
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe  
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe  
4=very severe 
0 = 0%  
1 = 1% - 9%  
2 = 10% - 29%  
3 = 30% - 49%  
4 = 50% - 69%  
5 = 70% - 89%  
6 = 90% - 100% 
Trunk (T) 
Including 
axilla and 
groin area 
0=none  
1=slight  
2=moderate  
3=severe  
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe  
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe  
4=very severe 
0 = 0%  
1 = 1% - 9%  
2 = 10% - 29%  
3 = 30% - 49%  
4 = 50% - 69%  
5 = 70% - 89%  
6 = 90% - 100% 


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Upper Limbs 
(U) 
0=none  
1=slight  
2=moderate  
3=severe  
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe  
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe  
4=very severe 
0 = 0%  
1 = 1% - 9%  
2 = 10% - 29%  
3 = 30% - 49%  
4 = 50% - 69%  
5 = 70% - 89%  
6 = 90% - 100% 
Lower Limbs 
(L) 
Including 
buttocks area 
0=none  
1=slight  
2=moderate  
3=severe  
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe  
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe  
4=very severe 
0 = 0%  
1 = 1% - 9%  
2 = 10% - 29%  
3 = 30% - 49%  
4 = 50% - 69%  
5 = 70% - 89%  
6 = 90% - 100% 
#Percentage (not score) of body region (not whole body) affected will be recorded.  
Based on PASI, to be eligible a patient must have a score of 12 or more at screening 
and visit 2.  
Based on total BSA, to be eligible, a patient must have 10% or more total BSA 
involved at screening and visit 2.  
The following definitions are used in this study according to CHMP guidelines [16]: 
 PASI 75 response: patients achieving ≥ 75% improvement (reduction) in PASI 
score compared to baseline are defined as PASI 75 responders  
 
 PASI 50 response (partial response): patients achieving ≥ 50% improvement 
(reduction) in PASI score compared to baseline are defined as PASI 50 
responders 
9.3.2 
Investigator Global Assessment (IGA) 
The 5-point IGA mod 2011 scale has been developed based on a previous version of 
6-point IGA/PGA Scale based on inputs received from regulatory agency [28].  
The IGA mod 2011 used in this study is static, i.e. it refers exclusively to the patient’s 
current disease state at the time of the assessments, and does not attempt a comparison 
with any of the patient’s previous disease states, whether at baseline or at a previous 
visit. IGA mod 2011 will also be assessed by independent dermatologist and PI 
separately. Both the scores will be recorded in the eCRF. 
 
The 5-point IGA mod 2011 rating scale is provided in Table 8. Based on this scale, a 
patient will be eligible to participate in the study if the patient has an IGA mod 2011 
score of 3 or 4 at screening and Day 1. 


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Based on this scale, a patient will be considered as IGA 0 or 1 responder if the patient 
achieves a score of 0 or 1 and improves by at least 2 points on the IGA scale 
compared to baseline. 
Table 8: The IGA mod 2011 rating scale [28]  
Score 
Short 
Descriptor 
Detailed Description 
0 
Clear 
No signs of psoriasis; post-inflammatory hyperpigmentation may 
be present 
1 
Almost Clear 
No thickening; normal to pink coloration; no to minimal focal 
scaling 
2 
Mild 
Just detectable to mild thickening; pink to light red coloration; 
predominantly fine scaling 
3 
Moderate 
Clearly distinguishable to moderate thickening; dull to bright 
red, clearly distinguishable to moderate thickening; moderate 
scaling 
4 
Severe 
Severe thickening with hard edges; bright to deep dark red 
coloration; severe/coarse scaling covering almost all or all 
lesions 
9.3.3 
Dermatology Life Quality Index (DLQI) 
The Dermatology Life Quality Index (DLQI) is a 10-item general dermatology 
disability index designed to assess health-related quality of life in adult patients with 
skin diseases such as eczema, psoriasis, acne, and viral warts [29] .  
Scores range from 0 to 30, and higher scores indicate greater health-related quality-of-
life impairment. Additionally, each subscale of the DLQI may be analyzed separately. 
It will be completed in the language the patient is most familiar with, at the scheduled 
visit before he/she undergo clinical assessments by the investigator. The patient 
should be given sufficient space and time to complete the questionnaire. The principal 
investigator or designee should check the questionnaire for completeness and 
encourage the patient to complete any missing responses. The principal investigator or 
designee can explain the question, if required without influencing/guiding the 
response. The original questionnaires will be kept with the patient’s file as the source 
document. Completed questionnaires will be reviewed and examined by the 
investigator at the site after the clinical examination and efficacy assessments for 
other parameters, for responses that may indicate potential AEs or SAEs. The 
investigator should review not only the responses to the questions in the 
questionnaires but also for any unsolicited comments written by the patient. If AEs or 
SAEs are confirmed then the investigator must record the events as per section 10.0.  
Investigator should not encourage or influence the patient to change the responses 
reported in the completed questionnaire.  
9.3.4 
Photograph of the lesions 
PI should identify 1-2 index psoriasis lesions in each of the patients. At each visit 
indicated in Table 1, photography will be performed of these 1-2 index psoriasis 


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lesion(s) only. Index psoriasis lesion should have adequate severity (representative of 
overall severity, accessibility and re-evaluable at subsequent visits. If face (not 
preferable) lesion is required to be taken, then eyes must be masked or closed in all 
photographs. These photographs will be submitted to the sponsor to be retained as 
part of the patient’s medical record; however, they will not be analyzed proactively , 
will serve as supportive in terms of overall evaluation and may be analyzed 
retrospectively, after the study is complete, should there be gross differences in the 
PASI assessments by the PI and the independent dermatologists, at any site. In that 
case as well, this analysis will not override the independent dermatologists’ 
assessments.  
9.4 
Pharmacokinetics Assessments 
9.4.1 
Blood sampling 
Patients who will consent to participate in the PK part, samples will be collected at 
pre-defined period till 12 hours after the dosing of Week 4 (±2 days) visit. If required, 
metabolites of AUR101 can be assessed in the same samples. 
Blood samples (4 ml) will be taken at the following time points relative to dosing, for 
PK analysis: 
Time points: Pre-dose and 1, 3, 4, 5, 6, 8, 12 hours post-morning dose. 
Window period for blood collection will be 15 minutes for pre-dose and ±15 minutes 
for remaining time-points.  
It is expected that approximately 25 patients will provide the PK sampling. For these 
patients, evening dose should also be given after collection of 12th  hour sample.  
Note: Dosing should be done after taking standard locally acceptable food.  
9.5 
Sequence of Assessments 
During treatment visits (Visit 2 to 7), following sequence of assessments should be 
followed at the site: 
 Patient related questionnaire – DLQI filling 
 PASI, involved BSA and IGA assessment by Independent dermatologist 
 PASI, involved BSA and IGA assessment by investigator 
 Clinical examination, vitals, medical history, concomitant medication, AE 
assessment, photography and other study related procedures mentioned in 
Table 1 
 IP compliance check (Visit 3 onwards) 
 IP dispense according to IWRS  
 Dosing at the site followed by PK sampling in consenting patients at week 4 
(±2 days) visit. 
 
 


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10.0 
ADVERSE EVENTS 
10.1 
Definition of Adverse Event 
An AE is defined as any untoward medical occurrence in a subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal (investigational) product, whether or not 
related to the medicinal (investigational) product. 
Changes in clinical laboratory test results, vital signs and ECG results are to be 
recorded as AEs if they are judged to be clinically significant. 
Pre-planned or elective surgeries should be avoided during the conduct of the study. 
Pre-planned or elective surgeries or therapies should be recorded in the patient’s 
source documents but are not be considered AEs unless there is any change to the 
patient’s medical condition.  
SAE is defined as any untoward medical occurrence that at any dose:  
 results in death;  
 is life threatening;  
o requires inpatient hospitalization or prolongation of an existing 
hospitalization; results in persistent or significant disability/incapacity;   
Day care or outdoor surgery/procedure (e.g. stenting, Ryle’s tube 
insertion, tracheostomy cleaning, wound care, etc.) for prevention of any 
complication will not be considered as SAE but event leading to such 
procedure should be recorded as AE (if arise during the study period) or 
in medical history (if pre-existing condition)  
o Any planned hospitalization, such as hospitalization for PK sampling, 
will not be considered SAE.  
Note: Complications that occur during hospitalization are adverse events and if a 
complication prolongs hospitalization, then the event is serious;  
 results in a congenital anomaly/birth defect;  
 results in another important medical event that may not be immediately life 
threatening or does not result in death or hospitalization, but which may 
jeopardize the subject or may require medical or surgical intervention to 
prevent one of the outcomes listed above. 
Examples of important medical events which may meet the definition of a SAE 
include: intensive treatment in the emergency room or at home for allergic 
bronchospasm, certain abnormalities (e.g., blood dyscrasias), convulsions that do 
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10.1.1 Recording and follow-up 
For each patient, all AEs will be collected from informed consent through to the 
follow-up visit. AE assessment will be continuous throughout the study period. 
Pre-existing conditions (present at or before screening day; they will be recorded in 
medical history) are only to be recorded as AEs if the patient experiences a 
worsening or complication of the condition, and the description recorded in the 
CRF should clarify this. The onset of such an AE should correspond to the onset of 
the worsening of the pre-existing condition. 
For each AE, the following information will be recorded: 
 
AE description/term 
 
Treatment start and stop dates and times 
 
Frequency i.e. single episode or intermittent 
 
Severity: mild (easily tolerated), moderate (interferes with daily activities) or 
severe (prevents normal daily activities) 
 
Relationship to study drug (definite, probable, possible, unlikely or not related) 
 
Outcome (resolved, resolved with sequelae, or ongoing) 
 
Whether serious or not 
Definitions for the relationship to study drug assessment, to be made by the 
investigator, are as follows: 
o 
Definitely related: This category applies when, after careful medical 
consideration, there is almost no consideration of other causation. 
o 
Probably related: There is a clinically plausible time sequence between onset of 
the AE and study treatment administration. The AE is unlikely to be caused by a 
concurrent and/or underlying illness, other drugs, or procedures. If applicable, the 
AE follows a clinically consistent resolution pattern upon withdrawal of study 
drug. 
o 
Possibly related: There is a clinically plausible time sequence between onset of 
the AE and study treatment administration, but the AE could also have been 
caused by the concurrent/underlying illness, other drugs, or procedures. 
Information regarding study drug withdrawal may be lacking or unclear. 
“Possible” should be used when study treatment administration is one of several 
biologically plausible causes of the AE. 
o 
Unlikely related: The AE is most likely due to a non-study-treatment-related 
cause. However, association with the study treatment cannot be completely ruled 
out. 
o 
Unrelated: Another cause of the AE is most plausible, and a clinically plausible 
temporal sequence is inconsistent with the onset of the AE and study treatment 
administration and/or a causal relationship is considered biologically implausible. 


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For the purpose of regulatory reporting requirements, causal relationships of definite, 
probable, and possible will be considered treatment-related, while unlikely and 
unrelated will be considered not treatment-related. 
All AEs should be followed up until the AE resolves or the investigator considers 
that further follow-up is not necessary. 
Severity will be assessed by the investigator and will be graded as mild, moderate or 
severe.  
10.1.2 
Procedures for reporting SAEs 
All SAEs, regardless of relationship to the study treatment, must be reported to the 
Sponsor or designee within 24 hours of the Investigator becoming aware of the event. 
Written SAE notification must follow within the 24-hour reporting timeframe, via an 
SAE Report submitted to the Sponsor’s medical monitor via e-mail ID provided in 
Appendix A. Follow-up SAE reports must be submitted by the Investigator as new 
information becomes available. All treatment related SAEs should be followed until 
resolution, return to baseline, or stabilization.  
If the investigator becomes aware of safety information involving a patient who 
participated in the study that appears to be drug related, even after an individual 
patient has completed the study, this should also be reported to the Sponsor 
immediately.   
Sponsor will provide compensation for any drug related injury/death and medical 
management cost for drug related AEs, for a patient enrolled in India, according to 
applicable Central Drugs Standard Control Organization (CDSCO) regulations and as 
ordered by CDSCO, India. 
10.1.3 
Reporting to the IRB / ECs  
SAEs will be reported to the local Institutional Review Board (IRB) / EC by the 
Investigator as per regulatory and IRB requirements. Sponsor will also report to 
IRB/IEC as per applicable regulations 
10.1.4 
Reporting to the Regulatory Agency  
The Sponsor will be responsible for reporting all AEs and SAEs to the appropriate 
regulatory authority (e.g., U.S. Food and Drug Administration, CDSCO etc.) in 
accordance with respective guidelines.   
Investigators, and IRB/EC in accordance with all applicable local regulations and 
guidance.  
10.2 
Pregnancy Reporting  
Pregnancy testing must be performed in all female patients of childbearing potential 
throughout the study as specified in the Schedule of Events (Table 1), and the results 
of all pregnancy tests are to be recorded. In the event of a confirmed positive test 


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result, patients will be discontinued from study drug and will be followed for the 
outcome of their pregnancy.  
If a female patient suspects she might be pregnant (e.g., missed or late menstrual 
period) or a male patient suspects he may have fathered a child at any time during the 
study through the Follow-up visit, they must notify the Investigator immediately. The 
Investigator will follow the patient or patient’s partner to determine the outcome of 
the pregnancy.  
Information regarding pregnancy must be reported immediately to the Sponsor and 
the outcome information provided once the outcome is known. The Sponsor will be 
responsible for reporting all pregnancy cases to the appropriate regulatory authority 
(e.g., U.S. Food and Drug Administration, CDSCO etc.), Investigators, and IRB/EC 
in accordance with all applicable local regulations and guidance. 
11.0 
DATA MANAGEMENT AND STATISTICAL ANALYSIS 
11.1 
Sample Size Calculation 
AUR101 doses will be tested versus placebo with respect to the primary endpoint 
(PASI75 response). A sample size of 25 in each of the three arms will provide an 80% 
power with a one-sided Type I error of 0.05, if the true placebo response rate is 7% 
and the response rate on investigational arm(s) is 35%. The sample size is increased to 
30 to account for ~ 15-20% drop outs over the study period.  
Placebo response rates from previous studies was 4-7% in most of the studies in 
similar patient population [17-19].  
11.2 
Data Handling 
Data obtained in this study will be collected in eCRFs prepared by sponsor/designee. 
The eCRF will be completed and monitored in accordance with the principles of GCP. 
Source data is defined as all information in original records and certified copies of 
original records of clinical findings, observations, or other activities in a clinical trial 
necessary for the reconstruction and evaluation of the trial. Source documents are 
original documents, data and records, such as laboratory printouts, 12-lead ECG 
reports, dispensing records, and patient files. In case, any data is recorded directly into 
the eCRFs, then that will be considered as source and should be appropriately 
reflected in the study records. 
AEs, medical history, and pre-existing (concurrent) conditions will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA). Drugs will be coded using 
the World Health Organization (WHO) Drug Dictionary (WHO-DD). 
11.3 
Analysis Sets  
11.3.1 
Safety Population  
The Safety Population includes all patients in the study who receive at least one dose 
of AUR101.   


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11.3.2 
Efficacy Population  
Efficacy population will include patients who do not have any major protocol or 
inclusion/exclusion violations, have a valid baseline and at least one post-baseline 
(follow up) assessment for PASI score by the independent dermatologist.  
11.3.3 
Pharmacokinetic Population  
The Pharmacokinetic Population includes all patients in the study who receive any 
dose of AUR101 and provide samples for PK analysis.  
11.4 
Description of Statistical Analyses  
11.4.1 
General Considerations  
Data will be summarized using descriptive statistics (number of patients, mean, 
median, standard deviation, minimum, and maximum) for continuous variables and 
using frequencies and percentages for discrete variables. Data will be presented by 
treatment arms.  
A comprehensive statistical analysis plan (SAP) will be finalized prior to final data 
analysis.  
11.4.1.1 Medical history 
Any condition entered as medical history or current medical conditions at baseline 
will be coded using the MedDRA dictionary. They will be summarized by system 
organ class and preferred term of the MedDRA dictionary. 
11.4.1.2 Prior and concomitant medication 
Prior and concomitant medications will be summarized by treatment group in separate 
tables. 
Prior medications are defined as treatments taken and stopped prior to first dose of 
study treatment. Any medication given at least once between the day of first dose of 
randomized study treatment and the last day of study visit will be a concomitant 
medication, including those which were started pre-baseline and continued into the 
treatment period. 
Medications will be coded by WHO-DD. 
11.4.1.3 Handling of missing values 
The last observation carried forward method will be applied to all efficacy 
measurements (PASI score, IGA mod 2011 score, DLQI score etc.) that are missing 
for the respective visits when at least one post-baseline assessment is available.  
If all post baseline efficacy values are missing for one efficacy parameter then these 
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of the corresponding variable, i.e. it might be that the number of patients providing 
data for one variable is smaller than efficacy population. 
For patients who dropped out during study treatment period due to any reason, data 
from the last efficacy assessment will be considered for the primary endpoint and 
other secondary efficacy endpoints relevant at other future time-points as per Last 
Observation Carried Forward (LOCF) approach. Following the intent-to-treat 
principle for patients who prematurely discontinue treatment, but who are observed in 
the follow-up period, efficacy data collected in follow-up periods will be linked to 
planned but missed study visits as well. Detailed imputation schemes will be 
described in SAP.  
11.4.2 
Demographics and Baseline Characteristics  
Demographic and baseline characteristics, including age, sex, race, weight, medical 
history and conditions, prior anti-psoriasis therapy, and any other study-appropriate 
data will be tabulated and summarized.  
11.5 
Efficacy Analysis 
Summary statistics with 95% confidence interval will be presented for PASI, IGA 
DLQI scores. PASI 75, PASI 50 responses, IGA responders (patients achieving IGA 0 
or 1) will be summarized by treatment groups. Change from baseline in DLQI scores 
will be summarized by the treatment groups. Appropriate parametric or non-
parametric tests will be applied to test the significance between active arms vs. 
placebo. No multiplicity adjustments will be done.  
11.6 
Pharmacokinetic Analysis  
Individual plasma PK parameters, including but not limited to t1/2, AUC0-12, Kel, and 
CL/F.  Cmax, and Tmax will be estimated using appropriate compartmental or non-
compartmental models. Summaries of PK parameters will be presented by dose 
group.  
11.7 
Safety Analysis  
Safety observations and measurements will include AEs, vital signs and ECGs and 
clinical laboratory tests 
11.7.1 
Adverse Events  
Treatment-emergent adverse events (TEAEs) are signs or symptoms that occur during 
treatment or within 14 days of the last dose of study drug. These include new events 
absent at baseline or worsening of baseline conditions. Any adverse event considered 
related to treatment will also be considered a treatment-emergent adverse event 
(TEAE), regardless of the elapsed time since the last dose of study drug.  
AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). The number and percentages of patients experiencing AEs will be 
tabulated by system organ class (SOC), preferred term, maximum severity, and 


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relationship to AUR101. Summaries of the number of patients with DLTs, dose 
reductions/interruptions, SAEs, treatment-related AEs, AEs resulting in treatment/trial 
discontinuation, and deaths will be presented by dose cohort.   
11.7.2 
Vital Signs and ECG  
Vital signs at each visit and the change from baseline to each post-baseline assessment 
(after the first dose of study drug) will be summarized by treatment groups using 
descriptive statistics. This will include height (at screening only), weight, temperature, 
pulse rate, and blood pressure.  
ECG results will also be summarized by treatment groups. The percentage of patients 
with abnormal changes in vital signs during study drug administration will be 
summarized at each assessment.  
11.7.3 
Clinical Laboratory Tests  
Clinical laboratory test results will be summarized by treatment groups using 
descriptive statistics and will include hematology, chemistries, and urinalysis. 
Laboratory test values which are outside the normal range will be flagged as H (above 
high normal limit), L (below low normal limit), or A (abnormal) in the data listings. 
Laboratory values deemed clinically significant by the Investigator should be reported 
as AEs.  
11.8 
Interim Analysis  
An interim analysis may be done after 45 patients complete 12 weeks of treatment 
depending on the recruitment to evaluate early trends of efficacy or safety. It will be 
performed in such way that study team and sponsor will remain blinded for individual 
patients. A separate interim analysis plan will be prepared. Unblinded statistician will 
perform interim analysis who will not be part of the study statistical team.  Sample 
size may be adjusted, if required based on the results of the interim analysis.  
12.0 
STUDY ADMINISTRATION  
12.1 
Case Report Forms and Source Documentation  
For each patient, CRF and corresponding source records will be maintained at each 
clinical site. Case report forms should be completed in a timely manner, and every 
effort should be made to have forms completed and up-to-date in anticipation of a 
visit by the Sponsor’s monitor.  
The Investigator must prepare and maintain adequate and accurate records of all 
observations and other data pertaining to the clinical study for each study participant. 
All aspects of the study will be carefully monitored with respect to GCP and standard 
operating procedures for compliance with applicable government regulations. The 
study monitor will be an authorized individual designated by the Sponsor. The study 
monitor will have access to all records necessary to ensure integrity of the data and 
will periodically review the progress of the study with the Principal Investigator.  


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An electronic data capture system to manage data collection will be utilized during 
this trial.  The electronic data capture system is a software tool designed to ensure 
quality assurance and facilitate data capture during clinical trials. The system is fully 
compliant with US Code of Federal Regulations 21 Part 11.  
The Investigator will ensure the accuracy, completeness, and timeliness of the data 
reported to the Sponsor. Data collection processes and procedures will be reviewed 
and validated to ensure completeness, accuracy, reliability, and consistency. A 
complete audit trail will be maintained of all data changes. The Investigator (or 
designee) will cooperate with the Sponsor (or its representative(s)) for the periodic 
review of study documents to ensure the accuracy and completeness of the data 
capture system at each scheduled monitoring visit.  
12.2 
Investigator Documentation  
Study staff will maintain appropriate medical and research records for this study, in 
compliance with ICH E6 and regulatory and institutional requirements for the 
protection of confidentiality of patients. Study staff will permit authorized 
representatives of regulatory agencies to examine (and when required by applicable 
law, to copy) research records for the purposes of quality assurance reviews, audits, 
and evaluation of the study safety, progress and data validity.  
The Investigator will provide the Sponsor with an Investigator’s Undertaking 
according to Indian regulatory requirements, in addition to the fully executed FDA 
Form 1572 and his/her curriculum vitae. The investigator will indicate on Form 1572 
the name and location of the clinical laboratory which will be used for patient 
evaluation. The laboratory’s certification, certification number, and date of 
certification and the laboratory normal values will be provided. Any changes in the 
clinical laboratory will be provided promptly to the Sponsor who will report the 
changes to the FDA as required.  
12.3 
Record Retention  
Essential clinical documents will be maintained to demonstrate the validity of the 
study and the integrity of the data collected. Trial Master File and Site Master Files 
will be established at the beginning of the study, maintained for the duration of the 
study, and retained according to the appropriate regulations.  
The Investigator will also retain a copy of all study records in a secure location for a 
period as mutually agreed with sponsor in the Clinical Trials Agreement. Investigator 
will be advised when the record retention is complete and no longer needed.   
12.4 
Audit and Inspection Procedures  
Regulatory authorities, the Institutional Review Board (IRB)/Ethics Committee (EC), 
and/or the Sponsor’s clinical quality assurance group, or its designee, may request 
access to all source documents, eCRFs, and other study documentation for on-site 
audit or inspection. Direct access to these documents must be guaranteed by the 
Investigator, who must provide support at all times for these activities.  


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12.5 
Protocol Deviations and Amendment  
The Investigator is not permitted to alter or deviate from the protocol except when 
immediate health care concerns mandate it. All the protocol deviations should be 
appropriately documented.   
All protocol revisions (amendments) must originate with and be documented by the 
Sponsor. The Investigator must submit the amendment to his/her IRB/EC for review 
and approval prior to implementation. Documentation of approval signed by the 
chairperson or designee must be sent to the Sponsor.  
12.6 
Sponsor Monitoring  
Monitoring and auditing procedures approved by the Sponsor will be followed in 
order to comply with GCP guidelines. After satisfactory receipt of all necessary 
regulatory paperwork, the  
Sponsor’s monitor will arrange that all study material be delivered to the study site at 
a mutually convenient time. An initiation visit by the Sponsor/designee and its 
monitoring personnel will be made. At this meeting, all personnel expected to be 
involved in the conduct of the study will undergo an orientation to include review of 
study protocol, instruction for eCRF completion and overall responsibilities, including 
those for drug accountability and study file maintenance.  
Throughout the course of the study, the Sponsor or its designee’s monitor will make 
frequent contact with the Investigator. This will include telephone and/or on-site 
visits. On-site checking of the eCRFs for completeness and clarity, cross-checking 
with source documents, and clarification of administrative matters will be performed. 
As part of the data audit, it is expected that source documents (e.g., hospital records, 
office records) will be made available for review by the monitor. The monitor also 
will perform drug accountability checks, and may periodically request review of the 
Investigator’s study file to assure completeness of documentation in all respects of 
study conduct.  
Upon study completion, the monitor will arrange for a final review of the study files, 
after which the file should be secured by storage for the appropriate period as 
specified in Section 12.3.  
The Investigator or appointed delegate will receive the Sponsor’s representative 
during these on-site visits and will cooperate in providing the documents for 
inspection and responding to inquiries that may arise as part of this review. The 
Investigator will also permit inspection of the study files by authorized representatives 
of the FDA and regulatory authorities of other countries.  
12.7 
Publication/Data Sharing Policy  
Publication by the sites of any data from this study must be in accordance with the 
clinical trial agreement.  


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12.8 
Reports and Publications   
Upon completion of the trial (or early termination), the sponsor should provide the 
EC/IRB with a summary of the trial’s outcome. All the regulatory authorities will also 
be provided with reports, as required per local regulations.  
A clinical study report will be prepared by the sponsor or its designee in accordance 
with the ICH guidelines.  
13.0 
ETHICS/PROTECTION OF HUMAN PATIENTS  
13.1 
Ethical Conduct of the Study  
The study will be conducted in accordance with ethical principles that have their 
origin in the  
Declaration of Helsinki and are consistent with International Conference on 
Harmonisation, Good Clinical Practice guidelines, applicable regulatory requirements, 
and Sponsor policies. The investigator will ensure that this study is conducted in full 
conformity with the principles set forth in The Belmont Report: Ethical Principles and 
Guidelines for the Protection of Human Patients of Research, as drafted by the US 
National Commission for the Protection of Human Patients of Biomedical and 
Behavioral Research (April 18, 1979) and codified in 45 CFR Part 46 and/or the ICH 
E6.  
13.2 
Institutional Review Board (IRB)/Ethics Committee (EC)  
The protocol, informed consent form(s), recruitment materials, and all patient 
materials will be submitted to the IRB/EC by the investigator for review and approval. 
Approval of all Essential Documents including the protocol, informed consent form, 
and other patient pertinent documents etc.  must be obtained before any patient is 
enrolled at any given investigative center, and a copy of the approval letter supplied to 
the Sponsor or Sponsor’s designee. Any amendment to the protocol will require 
review and approval by the IRB/EC before the changes are implemented in the study. 
All ongoing patients shall be notified about the changes and asked to sign amended 
version of the informed consent form. 
During the course of the study, the Investigator shall make timely and accurate reports 
to the IRB/EC on study progress at intervals as advised by the investigative site or 
IRB/EC standard operating procedures. Copies of all reports to, and correspondence 
with, the IRB/EC must be provided to the Sponsor or Sponsor’s designee. Further, 
after the completion or early termination of the study, a final report should be 
submitted by the Investigator to the respective IRB/EC following the IRB/EC SOP 
and share the notification and acknowledgement with the Sponsor.  
It is the Investigator’s obligation to maintain an IRB/EC correspondence file and to 
make this available for review to Sponsor representatives as part of the routine study 
monitoring process.  


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13.3 
Informed Consent  
Informed consent is a process that is initiated prior to the individual agreeing to 
participate in the study and continues throughout study participation. Extensive 
discussion of risks and possible benefits of study participation will be provided to 
patients and their families, if applicable. A consent form describing in detail the study 
procedures and risks will be given to the patient. Before each patient is enrolled in the 
clinical study, written informed consent will be obtained from the patient according to 
the regulatory and legal requirements of the participating country. Specifically, for 
any patients enrolled from sites in India (as per the regulatory requirement), the 
Informed Consent Form (ICF) will also contain the language that patients enrolled in 
the trial will receive free medical management for any injury occurring to him/her 
while participating in the study, as long as required in the opinion of the investigator, 
or till such time it is established that the injury is not related to the clinical trial, 
whichever is earlier. Further the ICF, for patients enrolled in India, will also state that 
in case of study related injury or death or permanent disability, the Sponsor / designee 
will provide financial compensation to the patient / nominee as per the order of the 
licensing authority.   
The patient will receive all information that is required by regulatory authorities and 
ICH guidelines. The Investigator (or designee) will provide the Sponsor with a copy 
of the IRB/EC approved ICF prior to the start of the study. The ICF must be signed 
and dated by investigator and patient; one copy will be given to the patient for their 
records whereas original will be retained by the Investigator as part of the clinical 
study records. Impartial witness should sign and date the ICF, if consenting patient is 
illiterate and patient’s thumb impression should also be taken. The investigator will 
not undertake any investigation specifically required for the clinical study until 
written consent has been obtained. The terms of the consent and when it was obtained 
must also be documented. Patients will be given the opportunity to discuss the study 
with their surrogates or think about it prior to agreeing to participate. They may 
withdraw consent at any time throughout the course of the study. The rights and 
welfare of the patients will be protected by emphasizing to them that the quality of 
their clinical care will not be adversely affected if they decline to participate in this 
study.  
If a protocol amendment is required, then the ICF may need to be revised to reflect the 
changes to the protocol. If the ICF is revised, it must be reviewed and approved by the 
responsible IRB/EC and signed by all patients subsequently enrolled in the clinical 
study as well as those ongoing in the clinical study before implementing revised ICF.  
Written informed consent will be obtained and documented from each patient prior to 
entry into the study. The consent process will be documented in the source and 
applicable details should be transcribed in the e-CRF. Additionally, for patients 
enrolled in India, Audio-Visual consenting, for patients deemed vulnerable by the 
investigator, will also be required, as per CDSCO regulations.   
13.4 
Confidentiality and Data Protection  
All clinical study findings and documents will be regarded as confidential. Study 
documents (protocols, Investigator’s Brochures, and other materials) will be stored 


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appropriately to ensure their confidentiality. Patient data will be made available upon 
request to monitors from the Sponsor, the Food and Drug Administration, the 
Institutional Review Board, and to other government agencies that have responsibility 
for clinical research activities.  
The anonymity of participating patients must be maintained. Data that is released by 
the Investigator to the Sponsor, the FDA, or IRB will not be directly traceable to the 
patient.  
Documents that identify the patient (e.g., the signed informed consent document) 
must be maintained in confidence by the Investigator. In the event that a publication 
of this research incorporates a patient's medical data, that data will not identify the 
patient. 
 
 


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14.0  REFERENCES 
1. Coffman RL. Origins of the T(H)1-T(H)2 model: a personal perspective. Nat 
Immunol. 2006;7(6):539–41. 
2. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, et al. Interleukin-
23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation 
of the brain. Nature. 2003;421:744–8. 
3. Wang Y, Kumar N, Solt LA, Richardson TI, Helvering LM, Crumbley C, et al. 
Modulation of retinoic acid receptor-related orphan receptor alpha and gamma 
activity by 7-oxygenated sterol ligands. J Biol Chem. 2010;285:5013–25. 
4. Santori FR. Nuclear hormone receptors put immunity on sterols. Eur J Immunol. 
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5. Jin L, Martynowski D, Zheng S, Wada T, Xie W, Li Y. Structural basis for 
hydroxycholesterols as natural ligands of orphan nuclear receptor RORgamma. 
Mol Endocrinol. 2010;24:923–9. 
6. Lubberts E. The IL-23-IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol. 
2015;11:562. 
7. Gaffen SL, Jain R, Garg AV, Cua DJ. The IL-23-IL-17 immune axis: from 
mechanisms to therapeutic testing. Nat Rev Immunol. 2014;14:585–600. 
8. Marta Catarina Esteves Guedes, Luis Miguel Borrego, and Rui Daniel Proença. 
Roles of interleukin-17 in uveitis. Indian J Ophthalmol. 2016 Sep;64(9):628–34. 
9. Ruan Q, Kameswaran V, Zhang Y, Zheng S, Sun J, Wang J, et al. The Th17 
immune response is controlled by the Rel-RORgamma-RORgamma T 
transcriptional axis. J Exp Med. 2011;208(11):2321–33. 
10. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal 
develop-mental pathways for the generation of pathogenic effector TH17 and 
regulatory T cells. Nature. 2006;441:235–38. 
11. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. TGFbeta in the 
context of an inflammatory cytokinemilieu supports de novo differentiation of IL-
17-producing T cells. Immunity. 2006;24:179–89. 
12. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO, et 
al. Transforming growth factor-beta induces development of the T(H)17 lineage. 
Nature. 2006;441:231–34. 
13. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The 
orphan nuclear receptor RORgammat directs the differentiation program of 
proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121–33.  


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14. Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 
2007 Jul 21;370(9583):263-271. 
15. ICH E10. Choice of Control Group and Related Issues in Clinical Trials. May 
2001 
16. Committee for medicinal products for human use (CHMP), European Medicines 
Agency for the Evaluation of Medicines for Human Use. (2004) Guideline on 
clinical investigation of medicinal products indicated for the treatment of psoriasis. 
CHMP/EWP/2454/02 corr document. London, UK. 
17. Papp KA, Tyring S, Lahfa M, Prinz J, Griffiths CE, Nakanishi AM, et al. A global 
phase II randomized controlled trial of etanercept in psoriasis: safety, efficacy, and 
effect of dose reduction. Br J Dermatol. 2005 Jun;152(6):1304-12. 
18. Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, et al.  
Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal 
antibody, in patients with psoriasis: 52-week results from a randomised, double-
blind, placebo-controlled trial (PHOENIX 2). Lancet; 2008 May 17; 
371(9625):1675-84. 
19. Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, et al. 
Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal 
antibody, in patients with psoriasis: 76-week results from a randomised, double-
blind, placebo-controlled trial (PHOENIX 1). Lancet; 2008 May 17; 
371(9625):1665-74. 
20. AIN457 Regimen Finding Study in Patients With Moderate to Severe Psoriasis 
https://clinicaltrials.gov/ct2/show/study/NCT00941031 (accessed on 06 Aug 2019) 
21. Papp K, Reich K, Leonardi CL, Kircik L, Chimenti S, Langley RG, et al. 
Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with 
moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled 
trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis 
[ESTEEM] 1). J Am Acad Dermatol. 2015 Jul; 73(1):37-49. 
22. Papp KA. A phase 2 study demonstrating the efficacy and safety of the oral 
therapy CC-10004 in subjects with moderate to severe psoriasis. J Am Acad 
Dermatol. 2008. Abstract P2614 
23. Menter A1, Tyring SK, Gordon K, Adalimumab therapy for moderate to severe 
psoriasis: A randomized, controlled phase III trial. J Am Acad Dermatol. 2008 
Jan; 58(1):106-15. Epub 2007 Oct 23. 
24. Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, et al. 
Secukinumab in Plaque Psoriasis — Results of Two Phase 3 Trials. N Engl J Med. 
2014 Jul 24; 371(4):326-38. 
25. Fredriksson T, Pettersson U (1978) Severe psoriasis—oral therapy with a new 
retinoid. Dermatologica; 157:238–44. 


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26. Gottlieb AB, Griffiths CE, Ho VC, Lahfa M, Mrowietz U, Murrell DF, et al. 
Efficacy and tolerability of oral pimecrolimus in the treatment of moderate to 
severe chronic plaque type psoriasis: a double-blind, multicentre, randomized 
dose-finding trial. Br J Dermatol; 2005 Jun; 152(6):1219-27. 
27. Weisman S, Pollack CR, Gottschalk RW Psoriasis disease severity measures: 
comparing efficacy of treatments for severe psoriasis. J Dermatolog Treat; 2003 
14: 158-165. 
28. Langley RG, Feldman SR, Nyirady J, van de Kerkhof P, Papavassilis C. The 5-
point Investigator's Global Assessment (IGA) Scale: A modified tool for 
evaluating plaque psoriasis severity in clinical trials. J Dermatolog Treat. 2015 
Feb;26(1):23-31. 
29. Finlay AY and Khan GK (1994) Dermatology Life Quality Index (DLQI): A 
simple practical measure for routine clinical use. Clin Exp Dermatol; 19:210-216. 


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Appendix A: Pharmacovigilance Contact Details 
 
Pharmacovigilance Department  
Veeda Clinical Research  
Nr. YMCA club, S. G. Highway,  
Ahmedabad- 380015, Gujarat, India 
Email: drugsafety@aurigene.com (SAE form is to be sent on this e-mail ID) 
Fax Number: +91 7930013010 
 
 
 
 


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Appendix B: Clinical Laboratories and Other Departments and/or Facilities 
Participating in the Study 
 
Clinical Laboratory Facility (Central Laboratory) 
Metropolis Healthcare Limited,  
250-D, Udyog Bhavan, 
Hind Cycle Marg, 
Behind Glaxo, 
Worli, Mumbai – 400030 
Customer care: 022-33993939 
 
Bioanalytical Laboratory Facility for Pharmacokinetic samples 
Veeda Clinical Research Pvt Ltd.,  
2nd, 3rd, 4th Floor Shivalik Plaza-A, Nr. ATIRA, IIM Road,  
Ahmedabad-380015, Gujarat, India 
Phone: +91 79 3001 3000 
 
Data Management and Statistical Services 
JSS Medical Research India Pvt. Ltd. 
6th Floor, Vatika Mindscapes, Tower-B 
Near Sarai Khwaja Metro Station, Mathura Road 
NH-2, Sector 27D  
Faridabad – 121003 India. 
Phone: +91-129-6613500 
Fax: +91-129-6613520 
 
This and any “Appendix” can be changed administratively, without the 
need for an amendment. 

SAP_001.pdf: 
 
JSS Medical Research India Private Limited   
Data Management 
 
Title: Statistical Analysis Plan-Module I 
SOP Number: 
JSS-DM-BIS-01 
Current Version Number: 1.0 
Previous Version Number: Nil 
Document Date: 
25MAR2021 
 
 
 
Protocol No.  AUR101-201                                                       Confidential                                              
25MAR2021 
JSS-DM-BIS-01 v 11.0 – Annexure I                                                                                                                      Page 1 of 37 
                                      
STATISTICAL ANALYSIS PLAN 
 
Protocol Title: 
A Phase II, Multicenter, Double-blind, Double 
Dummy, 
Placebo 
Controlled, 
Randomized, 
Study to Evaluate the Efficacy and Safety of two 
doses of AUR101 (600mg and 400mg) in 
patients 
with 
Moderate-to-Severe 
Psoriasis 
(INDUS-2) 
 
Protocol No.:  
AUR101-201 
Protocol Date: 
07AUG2019 
SAP Version:  
1.0 
SAP Date: 
 
25MAR2021 
 
 
Prepared By: 
 
JSS Medical Research India Private Limited 
Data Management 
Tower 2, 1st Floor, South Wing 
L&T Business Park 
Plot no 12/4, Sector 27 D, Near Sarai Khawaja Metro Station 
Delhi Mathura Road, Faridabad -121003, Haryana, India 
Landline No. +(91)129 – 6613500 
Fax No. +(91)129 - 6613520 
 
 
Sponsor: 
Aurigene Discovery Technologies Limited 
(Subsidary of Dr. Reddy’s Laboratories Limited) 
39-40, KIADB Industrial Area, Phase II,  
Electronic City Hosur Road,  
Bangalore- 560100, Karnataka, India 


 
JSS Medical Research India Private Limited   
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Title: Statistical Analysis Plan-Module I 
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Current Version Number: 1.0 Previous Version Number: Nil 
Document Date: 
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Protocol No.  AUR101-201                                                       Confidential                                              
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JSS-DM-BIS-01 v 11.0 – Annexure I                                                                                                                      Page 2 of 36 
                                      
Sponsor Signature 
 
I hereby declare that I have reviewed the Statistical Analysis Plan and agree to its form and 
content.  In addition, I confirm that the outlined Statistical Analysis Plan contains all 
relevant information for the data analysis to be performed in the Protocol No. AUR101-201 
study by the Biostatistics Department. 
 
 
 
 
 
 
Represented by: 
___________________________________________ 
              _______________ 
 
  Date 
Dr. Divyesh Mandavia 
Senior Manager, Clinical Development 
Aurigene Discovery Technologies Ltd.  
 
 
 
26Mar2021


SS 
JSS Medical Research India Private Limited 
390HSVE 
AURIGENE 
Data Management 
ww. 
Title: Statistical Analysis Plan-Module I 
SOP Number: 
Document Date: 
JSS-DM-BIS-01 
Current Version Number: 1.0 Previous Version Number: Nil 
25MAR2021 
Authorization Document 
Anjali Yadav 
Biostatistician 
25MAR2021 
Author 
Designation 
Signature 
Date 
Ayush Srivastava 
Biostatistician 
25MAR2021 
Reviewer 
Designation 
Signaturee 
Date 
Devyani Kanojia 
Project Lead 
25MAR2021 
Reviewer 
Designation 
Signature 
Date 
Dr Vinay Gupta 
Senior Manager 
Biostatistics 
Approver 
Designation 
Signature 
Date 
Protocol No. AURI01-201 
Confidential 
25MAR2021 
JSS-DM-BIS-01 v 11.0-Annexure I 
Page 3 of 37 


 
JSS Medical Research India Private Limited   
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Title: Statistical Analysis Plan-Module I 
SOP Number: 
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Previous Version Number: Nil 
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25MAR2021 
 
 
 
Protocol No.  AUR101-201                                                       Confidential                                              
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Revision History 
 
Version # 
Version Date 
Author 
Description of Modifications from 
Previous Version 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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JSS-DM-BIS-01 v 11.0 – Annexure I                                                                                                                      Page 5 of 37 
                                      
Table of Contents 
1.0 
INTRODUCTION........................................................................................................................ 11 
2.0 
DESCRIPTION OF THE PROTOCOL .................................................................................... 11 
2.1 
Protocol Number ............................................................................................................................ 11 
2.2 
Protocol Title ................................................................................................................................. 11 
2.3 
Date and Version............................................................................................................................ 11 
2.4  
Study Background .......................................................................................................................... 11 
2.5  
Study Rationale .............................................................................................................................. 12 
3.0 
STUDY OBJECTIVES AND ENDPOINTS .............................................................................. 12 
3.1.1 
Primary Objectives......................................................................................................................... 12 
3.1.2 
Secondary Objectives..................................................................................................................... 12 
3.2.1 
Primary Endpoint(s) ....................................................................................................................... 13 
3.2.2 
Secondary Endpoint(s) ................................................................................................................... 13 
3.2.3 
Secondary Safety Endpoint ............................................................................................................ 13 
3.2.4 
Pharmacokinetic Endpoints ........................................................................................................... 13 
3.2.6 
Efficacy & Safety Evaluation score description ............................................................................ 14 
3.2.6.1  PASI (Psoriasis Area and Severity Index) ..................................................................................... 14 
3.2.6.2 
Investigator Global Assessment (IGA) .......................................................................................... 16 
3.2.6.3  Dermatology Life Quality Index (DLQI)....................................................................................... 16 
4.0 
STUDY METHODS..................................................................................................................... 16 
4.1 
Study Design and Plan ................................................................................................................... 16 
4.1.1    
Number of Patients and Duration of Treatment ............................................................................. 17 
4.1.2 
Formulation and Mode of Administration ..................................................................................... 17 
4.2 
Study Initiation and Completion .................................................................................................... 17 
4.3 
Selection of Study Population ........................................................................................................ 17 
4.3.1 
Screened Population....................................................................................................................... 18 
4.3.2     Randomized Population ................................................................................................................. 18 
4.3.3     Safety Population ........................................................................................................................... 18 


 
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4.3.4 
Efficacy population ........................................................................................................................ 18 
4.3.5 
Major Protocol Deviations ............................................................................................................. 18 
4.3.6     Pharmacokinetic (PK) Population .................................................................................................. 19 
4.4 
Schedule of Visits and Procedures ................................................................................................. 19 
4.5 
Permitted therapy for psoriasis ...................................................................................................... 21 
4.6 
Rescue Medication ......................................................................................................................... 21 
5.0      GENERAL CONSIDERATIONS FOR STATISTICAL ANALYSIS ........................................ 22 
5.1 
Sample Size Determination ............................................................................................................ 22 
5.2       
Compliance .................................................................................................................................... 22 
5.3 
Definition and Derived Variables .................................................................................................. 22 
5.3.1 
Baseline .......................................................................................................................................... 23 
5.3.2 
Change from Baseline .................................................................................................................... 23 
5.3.3 
End of Treatment ........................................................................................................................... 23 
5.3.4 
Treatment Start Day ....................................................................................................................... 23 
5.3.5 
Treatment End Day ........................................................................................................................ 23 
5.3.6 
Duration of Treatment Exposure ................................................................................................... 23 
5.4 
Methods for Withdrawals, Missing Data, and Outliers ................................................................. 24 
5.5 
Analysis Software .......................................................................................................................... 25 
5.6  
Change from Protocol .................................................................... Error! Bookmark not defined. 
6.0 
GENERAL CONSIDERATIONS FOR STATISTICAL ANALYSIS .......................................... 25 
6.0 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ................................ 27 
6.1 
Demographics ................................................................................................................................ 27 
6.2 
Prior and concomitant medication ................................................................................................. 28 
6.3 
Baseline and Screening Conditions................................................................................................ 28 
6.3.1 
Baseline Medical History ............................................................................................................... 28 
6.3.2 
Other Screening Assessments ........................................................................................................ 28 
7.0 
EFFICACY ANALYSES............................................................................................................. 28 
7.1    
Primary Efficacy Analysis ............................................................................................................. 28 
7.2       
Secondary Efficacy Analysis ......................................................................................................... 29 


 
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7.3  
Additional Analysis ....................................................................................................................... 31 
7.5       
Pharmacokinetic (PK) Analysis ..................................................................................................... 32 
8.0     SAFETY & TOLERABILITY ASSESSMENT ANALYSIS......................................................... 32 
8.1 
Adverse Events .............................................................................................................................. 33 
8.2 
Physical Examination..................................................................................................................... 33 
8.3        Vital Signs ...................................................................................................................................... 33 
8.4 
ECG ............................................................................................................................................... 34 
8.5       
 Laboratory Parameters .................................................................................................................. 34 
8.6      
Urine Pregnancy Test ..................................................................................................................... 34 
9.0 
REPORTING CONVENTIONS ................................................................................................. 34 
9.1 
Reporting of Numeric Values ........................................................................................................ 34 
10.0 
OUTPUT (TABLES, LISTINGS AND GRAPHS) CONSIDERATIONS .............................. 35 
11.0 
REFERENCES .............................................................................................................................. 36 
 


 
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List of Abbreviations and Definition of Terms 
Abbreviation 
Definition 
 AE  
 Adverse Events 
 ALP  
 Alkaline Phosphatase 
 ALT  
 Alanine Aminotransferase 
 AST  
 Aspartate Aminotransferase 
 AUC  
 Area under the plasma concentration 
 AUC0-∞ 
 AUC0-∞ Area under the plasma concentration-time curve   from time 0 to infinity 
 AUC0-t  
Area under the plasma concentration-time curve from time 0 to t hours calculated using the 
linear trapezoidal rule 
 AUClast  
last Area under the plasma concentration-time curve from time 0 to the last measurable    
concentration at time (t) calculated using the linear trapezoidal rule 
 Beta-HCG  
 Beta-Human Chorionic Gonadotropin 
 BCRP  
 Breast Cancer Resistant Proteins 
 BID  
 Twice daily 
 BMI  
 Body Mass Index 
 BSA  
 Body Surface Area 
 BUN  
 Blood Urine Nitrogen 
 CI  
 Confidence Interval 
 CL/F 
 CL/F Plasma Clearance 
 Co-I  
 Co-Investigator 
 CDSCO  
 Central Drugs Standard Control Organization 
 Cmax  
Maximum plasma drug concentration from plasma concentration time profile 
 CRF  
 Case Report Form 
 CT  
 Computerized tomography 
 CYP  
 Cytochromes P450 
 DCGI  
 Drugs Controller General of India 
 DBL  
 Data Base Lock 
 DLQI  
 Dermatology Life Quality Index 
 DLT 
 Dose Limiting Toxicity 
 ECG  
 Electrocardiogram 
 eCRF 
 electronic Case Report Form 
 FDA 
 Food and Drug Administration 
 FIH  
 First in Human 
 FTIH  
 First Time in Human 
 GCP  
 Good Clinical Practice 
 GGT  
 Gamma-Glutamyl Transpeptidase 


 
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 GLP  
 Good Laboratory Practice 
 GMP  
 Good Manufacturing Practice 
 HBsAg  
 HBsAg  
 HCV Ab  
 Hepatitis C Virus Antibody 
HED  
 Human Equivalent Dose 
HIV  
Human Immunodeficiency Virus 
ICF  
 Informed Consent 
ICH  
 International Conference on Harmonization 
IGA  
 Investigator Global Assessment 
IL-17  
 Interleukin-17 
IL-23  
 Interleukin-23 
IRB/ EC  
 Institutional Review Board /Ethics Committee 
 SAP  
Statistical Analysis Plan 
 ITT 
 Intent to Treat 
IUD  
 Intrauterine Device 
IWRS  
 Integrated Web based Randomization system 
 JSS India 
 JSS Medical Research India Private Limited 
Kel  
 Kel Elimination Rate Constant 
LOCF  
 Last Observation Carried Forward 
MCH  
 Mean Corpuscular Hemoglobin 
MedDRA  
 MedDRA Medical Dictionary for Regulatory Activities 
NOAEL  
 No-Observed-Adverse-Effect Level 
PASI  
 Psoriasis Area and Severity Index 
PD  
 Pharmacodynamics 
PGA  
 Physician Global Assessment 
P-gp  
 P-glycoprotein 
PI  
 Principal Investigator 
 PK  
 Pharmacokinetics 
PO  
 Per oral 
QD  
 Once a day 
QFT  
 QuantiFERON TB-Gold test 
 RORγ  
 Retinoic Acid Related Orphan Receptor Gamma 
 SD  
 SD Standard Deviation 
 SAE  
 SAE Serious Adverse Event 
 SOC  
 SOC System organ class 
 t½  
  t½ Terminal elimination half-life 
 TEAEs  
 TEAEs Treatment emergent adverse events 
 TGF  
 TGF Transforming Growth Factor 
 TNF  
 TNF Tumor necrosis factor 


 
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 Th  
 Th Helper T cells 
 Tmax  
 Tmax Time to reach Cmax 
 ULN  
 ULN Upper Limit of Normal 
 WBCs  
 WBCs White blood cells 
 WHO-DD  
 World Health Organization Drug Dictionary 


 
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1.0 
INTRODUCTION 
This Statistical Analysis Plan (SAP) describes a comprehensive and detailed 
description of strategy and statistical technique to be used to realize the analysis of 
data for Aurigene Discovery Technologies Limited protocol AUR101-201. (A Phase 
II, Multicenter, Double-blind, Double-dummy, Placebo controlled, Randomized, 
Study to Evaluate the Efficacy and Safety of two doses of AUR101 in patients with 
Moderate-to-Severe Psoriasis (INDUS-2)).  
This phase II study is conducted to assess the safety and efficacy of two doses of 
AUR101 – An oral RORγT inhibitor for anti-inflammatory disorders in patient with 
Moderate-to-Severe Psoriasis. The reader of this SAP is encouraged to also read the 
clinical protocol for details on the conduct of this study and the operational aspects of 
clinical assessments and timing for completing a patient in this study.  
The purpose of this analysis is to evaluate early trends of efficacy signals arising from 
this Phase II study which can help to plan AUR101 clinical development program. 
The planned analyses identified in this SAP can be used for amendment of current 
protocol to change the sample size, manuscript writing or presentation at conferences, 
and/or regulatory submissions. In addition, exploratory analyses not necessarily 
identified in this SAP may be performed to support the clinical development program. 
Any post-hoc, or unplanned, analyses not identified in this SAP performed will be 
clearly identified in the respective report. 
2.0 
DESCRIPTION OF THE PROTOCOL 
2.1 
Protocol Number 
AUR101-201 
2.2 
Protocol Title 
A Phase II, Multicenter, Double-blind, Double-dummy, Placebo controlled, 
Randomized, Study to Evaluate the Efficacy and Safety of two doses of AUR101 in 
patients with Moderate-to-Severe Psoriasis (INDUS-2).  
2.3 
Date and Version 
07 Aug 2019, Version 1.0 
2.4  
Study Background  


 
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Helper T cells (Th) have traditionally been divided into Th1 and Th2 subtypes. A 
thirds subtype of Th17 cell was shown to be dependent upon interleukin 23 (IL-23) 
stimulation and produces IL-17 in response to antigen recognition.[1,2] The 
differentiation of this cell type and the consequent production of IL-17 is dependent 
upon the transcription factor Retinoic acid related orphan receptor gamma (RORγ).  
 
Different studies suggest a causative involvement of IL-23 immune axis and Th17 
cytokines in different autoimmune diseases such as psoriasis, ankylosing spondylitis, 
psoriatic arthritis, etc. [3-5] RORγ is therefore expected to have a central role in driving 
these pathologies. Clinical validation of the IL-17 pathway is already proven from the 
therapeutic efficacy of antibodies that neutralize Th17-associated cytokines and 
receptors (secukinumab, ixekizumab-IL-17, ustekinumab-IL12/23, guselkumab, 
tildrakizumab-IL23 and brodalumab-IL-17 receptor A) in moderate to severe psoriasis 
and other autoimmune disorders such as psoriatic arthritis and ankylosing 
spondylitis).[3,4,6] In view of all these, AUR101 being an RORγ inhibitor, reduces IL-
17 and may prove effective in these diseases. 
2.5  
Study Rationale 
AUR101 is a potent and selective inhibitor of RORγ with good cellular activity in 
Th17 differentiation assays. The compound has also demonstrated good efficacy in 
relevant animal models. Toxicology studies with the compound have also 
demonstrated a favorable safety profile at the exposures showing efficacy in animal 
models. A completed FIH study has determined a desirable safety, PK and optimal IL-
17 inhibition, when AUR101 is administered at 600 mg BID. 
 
In view of favorable preclinical safety, preclinical efficacy, and PK, PD and safety 
data derived from FIH study, the current Phase II Proof of Concept (POC) study has 
been planned in moderate-to-severe psoriasis.   
3.0 
STUDY OBJECTIVES AND ENDPOINTS 
3.1.1 Primary Objectives 
The primary objective of the study is to assess efficacy of AUR101 in patients with 
moderate-to-severe psoriasis. 
3.1.2 Secondary Objectives 
The secondary objectives of the study are as follows, 


 
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1. To evaluate the safety and tolerability of two oral doses of AUR101 in patients with 
moderate-to-severe psoriasis. 
2. To evaluate the plasma pharmacokinetics of AUR101 in patients with moderate-to-
severe psoriasis 
3. To evaluate effect of AUR101 on quality of life in patients with moderate-to-severe 
psoriasis. 
3.2.0 End Points 
3.2.1 Primary Endpoint(s) 
Proportion of patients achieving PASI 75 (i.e. 75% reduction from baseline PASI 
score) at the end of week 12. 
3.2.2 Secondary Endpoint(s) 
1. Proportion of patients achieving PASI 75 (i.e. 75% reduction from baseline PASI 
score) at the end of week 4 and 8. 
2. Proportion of patients achieving PASI 50 (i.e. 50% reduction from baseline PASI 
score) at week 4, 8 and 12. 
3.  Proportion of patients achieving IGA 0 or 1 at week 4, 8 and 12. 
4. Percent change from baseline in PASI score at week 4, 8 and 12 
5. Change from baseline in IGA scale at week 4, 8 and 12 
6. Change from baseline to week 4, 8 and 12 in percent Body Surface Area (BSA) 
involved 
7. Change from baseline to week 4, 8 and 12 in Dermatology Life Quality Index (DLQI) 
3.2.3 Secondary Safety Endpoint 
Safety will be evaluated based on the nature and incidence of treatment emergent 
adverse events (AEs), vital signs, electrocardiograms (ECGs), laboratory assessments 
and physical examinations in patients treated with AUR101 or placebo. 
3.2.4 Pharmacokinetic Endpoints 


 
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Individual plasma PK parameters, including but not limited to t1/2, AUC0-12, Kel, and 
CL/F. Cmax, and Tmax will be estimated using appropriate compartmental or 
noncompartmental models. Summaries of PK parameters will be presented by dose 
group. 
 
3.2.5 Exploratory Endpoints 
 
While not stated in the study protocol, the sponsor will also explore the effects of 
AUR101 on PASI-90 as well as PASI-100 in the study.  
 
3.2.6 Efficacy & Safety Evaluation score description 
3.2.6.1 PASI (Psoriasis Area and Severity Index)  
PASI is widely used tool to measure the severity of psoriasis. It combines area of the 
lesions with severity of individual lesions by grading erythema, induration/thickness 
and scaling. It can be 0 (minimum) to 72 (maximum). A PASI score will be derived as 
indicated in Table 1.  
The following definitions are used in this study according to Committee for medicinal 
products for human use (CHMP) guidelines:  
 
 PASI 75 response: patients achieving ≥ 75% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 75 responders 
 PASI 50 response (partial response): patients achieving ≥ 50% improvement 
(reduction) in PASI score compared to baseline are defined as PASI 50 responders. 
 PASI 90 response: patients achieving ≥ 90% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 90 responders 
PASI 100 response: patients achieving 100% improvement (reduction) in PASI score 
(i.e. achieving PASI score of 0) compared to baseline are defined as PASI 100 
responders. 
 
 
Table 1. Psoriasis Area and Severity Index 
Body part  
Erythema 
(E)  
Thickening 
(plaque elevation, 
induration, I) 
Scaling 
(desquamation, 
D) 
Area score 
(based on true 
area %)# 
Head (H) 
including neck 
0=none 
1=slight 
0=none 
1=slight 
0=none 
1=slight 
0 = 0% 
1 = 1% - 9% 


 
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2=moderate 
3=severe 
4=very 
severe 
2=moderate 
3=severe 
4=very severe 
2=moderate 
3=severe 
4=very severe 
2 = 10% - 29% 
3 = 30% - 49% 
4 = 50% - 69% 
5 = 70% - 89% 6 
= 90% - 100% 
Trunk (T) 
Including 
axilla and 
groin area 
0=none 
1=slight 
2=moderate 
3=severe 
4=very 
severe 
0=none 
1=slight 
2=moderate 
3=severe 
4=very severe 
0=none 
1=slight 
2=moderate 
3=severe 
4=very severe 
0 = 0% 
1 = 1% - 9% 
2 = 10% - 29% 
3 = 30% - 49% 
4 = 50% - 69% 
5 = 70% - 89%  
6 = 90% - 100% 
Upper Limbs 
(U) 
0=none 
1=slight 
2=moderate 
3=severe 
4=very 
severe 
0=none 
1=slight 
2=moderate 
3=severe 
4=very severe 
0=none 
1=slight 
2=moderate 
3=severe 
4=very severe 
0 = 0% 
1 = 1% - 9% 
2 = 10% - 29% 
3 = 30% - 49% 
4 = 50% - 69% 
5 = 70% - 89% 6 
= 90% - 100% 
Lower Limbs 
(L) 
Including 
buttocks area 
0=none 
1=slight 
2=moderate 
3=severe 
4=very 
severe 
0=none 
1=slight 
2=moderate 
3=severe 
4=very severe 
0=none 
1=slight 
2=moderate 
3=severe 
4=very severe 
0 = 0% 
1 = 1% - 9% 
2 = 10% - 29% 
3 = 30% - 49% 
4 = 50% - 69% 
5 = 70% - 89% 6 
= 90% - 100% 
#Percentage (not score) of body region (not whole body) affected will be recorded. 


 
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3.2.6.2 Investigator Global Assessment (IGA) 
The 5-point IGA mod 2011 rating scale is provided in Table 2. Based on this scale, a patient 
will be considered as IGA responder if the patient achieves a score of 0 or 1 and improves by 
at least 2 points on the IGA scale compared to baseline. 
 
Table 2. Investigator Global Assessment 
Score 
Short Descriptor 
Detailed Description 
0  
 
Clear 
No signs of psoriasis; post-inflammatory 
hyperpigmentation may be present 
1 
Almost Clear 
No thickening; normal to pink coloration; no to 
minimal focal scaling 
2 
Mild 
Just detectable to mild thickening; pink to light red 
coloration; predominantly fine scaling 
3 
Moderate 
Clearly distinguishable to moderate thickening; 
dull to bright red, clearly distinguishable to 
moderate thickening; moderate scaling 
4 
Severe 
Severe thickening with hard edges; bright to deep 
dark red coloration; severe/coarse scaling covering 
almost all or all lesions 
 
3.2.6.3 Dermatology Life Quality Index (DLQI) 
The Dermatology Life Quality Index (DLQI) is a 10-item general dermatology 
disability index designed to assess health-related quality of life in adult patients with 
skin diseases such as eczema, psoriasis, acne, and viral warts. Scores range from 0 to 
30, and higher scores indicate greater health-related quality-of life impairment. 
Additionally, each subscale of the DLQI may be analyzed separately. 
In DLQI score, Minimal Clinically Important Difference (MCID) is considered as 5-
points reduction from baseline. [7-8]  
4.0 
STUDY METHODS 
4.1 
Study Design and Plan 
This is a multicenter, double-blind, double-dummy, placebo controlled, randomized 
study to evaluate efficacy and safety of two doses of AUR101 in patients with 
moderate-to-severe psoriasis. There are three arms – two arms of AUR101 (400 and 
600 mg BID) and one arm of placebo. 


 
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All the patients are followed up for 14 ± 2 days of their last dose for safety 
assessment. 
A subset up to 25 consenting patients will participate in the pharmacokinetic part in 
addition to main study. Separate consent will be taken. If patient consents for PK, 
samples will be collected at week 4 (±2 days) visit of dosing. 
4.1.1   Number of Patients and Duration of Treatment 
Approximately 90 patients with chronic moderate-to-severe chronic plaque psoriasis 
are randomized to each of the three arms (1:1:1) by IWRS as mentioned below:  
• 
AUR101 400 mg BID 
• 
AUR101 600 mg BID 
• 
Placebo BID 
All the patients will receive study drugs for 12 weeks in a double blind, double 
dummy fashion. 
4.1.2 Formulation and Mode of Administration 
AUR101 is formulated as 100 and 300 mg film coated tablets. Patients will take study 
drugs orally with water, twice daily after meals (breakfast and dinner), preferably 
same time each day.  
4.2 
Study Initiation and Completion 
This study is of approximately of 14 weeks from the screening through end of study. 
There will be seven scheduled visits and one follow up visit in the study. Follow-up 
visit will be 14 ±2 days after last dose tablet taken by the patients. 
4.3 
Selection of Study Population 
Adult males or females of age group between (18-65) years and confirmed diagnosis 
of chronic plaque-type psoriasis at least moderate severity, defined as (Psoriasis Area 
and Severity Index) PASI≥12 and involved Body Surface Area (BSA) ≥10 % at 
screening, diagnosed at least 6 months before screening and have willingness to give 
written informed consent and ability to adhere to the study restrictions and 
assessments schedule. 


 
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4.3.1 Screened Population 
The population will include all patients in the study who have signed Inform Consent 
Form. 
4.3.2    Randomized Population 
The Population will include all patients in the study who have signed Inform Consent 
Form and satisfied all inclusion and exclusion criteria. 
4.3.3    Safety Population 
The Safety Population will include all patients in the study who receive at least one 
dose of study treatment. 
4.3.4 Efficacy population 
Efficacy population will include patients who 
 
have a valid baseline and at least one post-baseline (follow up) assessment for 
PASI score by the independent dermatologist or withdrawal is associated with 
lack of effect by the patient before post-baseline assessment. 
 
do not have any major protocol or inclusion/exclusion violations,  
 
Efficacy population will provide sample for analysis of primary, secondary and 
exploratory endpoints. For patients who dropped out during study treatment period 
due to any reason, data from the last efficacy assessment will be considered for the 
primary endpoint and other secondary efficacy endpoints relevant at other future time-
points as per Last Observation Carried Forward (LOCF) approach. 
Efficacy data collected solely based on the photographs without on-site examination 
by the investigator/independent dermatologist will not be considered for the analysis 
and this data will also be imputed with LOCF approach.  
4.3.5 Major Protocol Deviations 
The protocol deviations in the study will be evaluated on a case-to-case basis and will 
be categorized as major or minor. A major protocol deviation is defined as any 
deviation that may affect the efficacy outcome or patient’s safety. Subjects having 
major protocol deviation will be finalized prior to the soft lock.  
 
Following are some protocol deviations. 
 
1. Violation of major inclusion/ exclusion criteria assessment 


 
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2. Use of prohibited concomitant medication  
3. Treatment non-compliance 
4. Non-compliance/non-assessment of study procedure 
5. Visit out of the window period 
4.3.6    Pharmacokinetic (PK) Population 
The Pharmacokinetic Population includes all patients in the study who receive any 
dose of AUR101 and provide samples for PK analysis.  
 
4.4 
Schedule of Visits and Procedures  
There will be seven scheduled visits and one follow up visit in the study mentioned as 
below: 
 Screening visit (Up to Day -14) 
 Visit 2: Randomization visit (Day 1) 
 Visit 3: Week 2 ±2 days  
 Visit 4: Week 4 ±2 days  
 Visit 5: Week 6± 2 days 
 Visit 6: Week 8 ±2 days  
 Visit 7: (End of Treatment): Week 12±4 days 
 
 Follow-up visit: 14 ±2 days after last dose 
All the procedures that will be conducted in different visits are shown in table 3. 


 
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Table 3. Study Activities 
Assessment 
Screening 
visit 
(Up to  
Day -14) 
Treatment Period 
Follow-up 
visit:  14 ± 
2 days 
after last 
dose 
Visit 2: 
Random
ization 
visit 
(Day 1) 
Visit 3: 
Week 
2 ±2 
days 
Visit 4: 
Week 4 
±2 days 
 
Visit 5: 
Week 
6± 2 
days 
Visit 6: 
Week 8 
±2 days 
Visit 7 
(End of 
Treatme
nt): 
Week 12 
±4 days 
Informed Consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Height (Only at 
Screening), BMI (only at 
screening), weight 
X 
X 
 
X 
 
X 
X 
 
Medical history 
X 
X 
X 
X 
X 
X 
X 
X 
Menstrual history in 
females 
X 
 
 
 
 
 
 
 
Prior/concomitant 
medication check 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs a 
X 
X 
X 
X 
X 
X 
X 
X 
QuantiFERON TB-Gold 
testb 
X 
 
 
 
 
 
 
 
Inclusion & exclusion 
criteria check 
X 
 
 
 
 
 
 
 
Inclusion & exclusion 
criteria verification 
 
X 
 
 
 
 
 
 
12 lead ECG  
X 
 
 
 
 
 
 
X 
Randomization 
 
X 
 
 
 
 
 
 
Photographs of lesions  
 
X 
X 
X 
X 
X 
X 
X 
Blood sampling for PKc 
 
 
 
X 
 
 
 
 
Clinical laboratory tests 
(Haematology, 
Biochemistry)  
X 
X 
 
X 
 
X 
X 
X 
Urinalysis 
 
X  
 
 
 
 
X  
 
Viral Serology 
X 
 
 
 
 
 
 
 
PASI score, IGA by 
independent evaluator and 
Investigator 
X 
X 
X 
X 
X 
X 
X 
X 
DLQI  
 
X 
X 
X 
X 
X 
X 
X 
IP dispense d 
 
X 
X 
X 
X 
X 
 
 
IP return and compliance 
check   
 
 
X 
X 
X 
X 
X 
 


 
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Assessment 
Screening 
visit 
(Up to  
Day -14) 
Treatment Period 
Follow-up 
visit:  14 ± 
2 days 
after last 
dose 
Visit 2: 
Random
ization 
visit 
(Day 1) 
Visit 3: 
Week 
2 ±2 
days 
Visit 4: 
Week 4 
±2 days 
 
Visit 5: 
Week 
6± 2 
days 
Visit 6: 
Week 8 
±2 days 
Visit 7 
(End of 
Treatme
nt): 
Week 12 
±4 days 
AE check 
 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test e 
X 
X 
 
X 
 
X 
X 
X  
AE = adverse event; ECG = electrocardiogram; PK = pharmacokinetic, IP= Investigational product, PASI=Psoriasis Area 
and Severity Index, IGA= Investigator Global Assessment 
a vital sign includes body temperature, blood pressure and pulse rate 
b Patients who are positive by QuantiFERON TB- Gold test, should undergo further workup according to investigator opinion 
(like Chest X-ray, CT scan of chest or any other locally acceptable method) to rule out active tuberculosis. 
c Only in subset of approximately 25 patients 
d As directed by IWRS; IP may be dispensed on additional or fewer days, as required by logistics 
e Serum pregnancy test at screening, and urine pregnancy test at other visits will be done for women of childbearing potential 
only 
4.5 
Permitted therapy for psoriasis 
Only bland emollients or shampoos (for scalp psoriasis) will be allowed during the   
study participation.  No active drug (topical or systemic) affecting psoriasis will be 
allowed during the treatment period.  
4.6 
Rescue Medication 
Rescue medication can be given if patient’s PASI score is increasing by at least 50% 
from baseline level at or after 6 weeks of therapy. In addition to above, if a patient has 
intolerable symptoms from psoriasis, then any available medication, including any 
biologic medications, such as secukinumab or adalimumab, can be administered as 
srescue medications. 
 
Patients who receive rescue treatment during the study treatment period will be 
considered treatment failures for the purpose of efficacy analysis. To conduct efficacy 
and safety assessments (e.g. disease severity scores, safety labs) immediately before 
administering any rescue treatment. Patients who receive “Rescue Medication” will be 
discontinued from the trial. All such patients should be followed up after 14 ±2 days 
of study drug discontinuation for safety assessment. 


 
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5.0      GENERAL CONSIDERATIONS FOR STATISTICAL  
  
ANALYSIS 
Data on continuous scale will be expressed as mean, standard deviation, standard 
error, median, 95%CI and number of patients in each treatment group. Categorical 
type of data will be presented with frequency and the percentages of patients in each 
treatment group. Statistical Analysis. Software (i.e. SAS® 9.4 or higher) will be used 
to perform all analyses. 
5.1 
Sample Size Determination 
AUR101 doses will be tested versus placebo with respect to the primary endpoint 
(PASI 75 response). A sample size of 25 in each of the three arms will provide an 
80% power with a one-sided Type I error of 0.05, if the true placebo response rate is 
7% and the response rate on investigational arm(s) is 35%. The sample size is 
increased to 30 to account for ~ 15-20% dropouts over the study period. Placebo 
response rates from previous studies was 4-7% in most of the studies in similar patient 
population. No multiplicity adjustments were considered in the sample size 
calculation as it is a POC study.  
 
A subset of approximately 25 consenting patients will participate in the 
pharmacokinetic part in addition to main study.  
5.2      Compliance 
IP return and compliance check will be assessed at visit 3, visit 4, visit 5, visit 6 and 
visit 7. Subjects will be dispensed 3 bottles at each visit. Each bottle contains total 30 
tablets and patients will have to take 3 tablets in the morning and 3 tablets in the 
evening.   
Total Compliance will be calculated by using formula: 
 
Total Compliance = Number of actual doses taken / (Number of expected doses to be taken) *100 
 
Overall compliance at each visit and during study period will also be calculated by 
using the above formula as given above. Descriptive statistics by treatment groups 
will be reported for treatment overall compliance using safety population. A listing 
will be provided.  
5.3 
Definition and Derived Variables 
 


 
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5.3.1 Baseline 
Baseline value is defined as the last non-missing assessment prior to the first study 
treatment exposure. If the last non-missing assessment is performed on the same date 
as the first study treatment and time is not available, the assessment will be considered 
as baseline. In this study, drug is dispensed at visit 2 that is randomization visit which 
will serve as baseline for efficacy variables. 
5.3.2 Change from Baseline 
Value of change from baseline at any post baseline visit is defined as the difference of 
the post-baseline value to the baseline value  
i.e. Change from baseline (∆) = post baseline value- baseline value 
Percent change from baseline is defined as percentage difference of the post-baseline 
value to the baseline value, relative to baseline value 
i.e. Percent Change from baseline at respective time =  
(Post baseline value at respective time - Baseline value) x 100 
 
 
 
Baseline value 
 
5.3.3 End of Treatment 
End of treatment value is defined as the last non-missing assessment at the end of 
study treatment visit i.e.  visit 7 (week 12 ± 4 Days). If the subject has not completed 
the treatment as per protocol, then the last available non-missing value prior to the end 
of study treatment visit will be used as end of study value and that visit will be 
considered as early termination visit. 
5.3.4 Treatment Start Day 
Date of first study treatment date is used for treatment start day i.e. visit 2 (day 1) in 
this study. 
5.3.5 Treatment End Day 
Date of last study treatment date is used for treatment end day until unless the subjects 
has not prematurely discontinued from the study, then the last date of treatment taken 
prior to the week 12 ± 4 Days will be used for treatment end day.  
5.3.6 Duration of Treatment Exposure 


 
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Duration of treatment exposure is defined as the time period in which the subjects was 
on treatment during the study and will be calculated as follows: number of days 
between the last dose date and the first dose date plus one i.e.  
Treatment duration=date of last dose -date of first dose +1. 
 
5.4 
Methods for Withdrawals, Missing Data, and Outliers 
 In case of a patient’s withdrawal from the study without any major protocol deviation, 
its values on subsequent visits will be considered missing.  
 
The last observation carried forward (LOCF) method will be applied to all efficacy 
measurements (PASI score, IGA mod 2011 score, DLQI score etc.) when at least one 
post-baseline assessment is available. If all post baseline efficacy values are missing 
for one efficacy parameter then these missing values will not be imputed and this 
patient will be removed from the analysis of the corresponding variable, i.e. it might 
be that the number of patients providing data for one variable is smaller than efficacy 
population. If withdrawal prior to first post-baseline assessment is considered due to 
lack of effect of the study drug by the investigator, then the respective patient will be 
considered as non-responder in PASI and IGA responder analysis, and no change (i.e. 
post-baseline difference of 0) will be considered for percent or absolute change in 
PASI, IGA or DLQI parameters.  
 
For missing safety variables, when repeat assessment data is available for the 
respective visit, then these repeat assessment data will be imputed. E.g. The 
hematology parameters are not available for Visit 4 for any patient and repeat 
hematology assessment is done prior to next scheduled visit, then hematology 
parameters during Visit 4 will be replaced with repeat assessment parameters.  
However, no values will be replaced if the parameter value is available. For example, 
if only ALT and AST are not available for a specific visit in biochemistry panel and 
repeat assessment prior to next visit is done with all liver function tests (ALT, AST, 
ALP, bilirubin, etc.), then only ALT and AST values will be replaced and other liver 
function values will not be replaced.  
 
For the efficacy variables (PASI score, IGA mod 2011 score, DLQI score), no 
observed values will be considered as outliers. For safety parameters like vital signs, 
lab parameters etc., any value which is out of range will be summarized as observed. 
However, it will be checked whether it is a normal or abnormal finding and will be 


 
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reported accordingly. For abnormal observed value we further summarized as 
clinically significance and non- clinically significance.   
 
 5.5 
Analysis Software 
Statistical processing will be performed using Statistical Analysis System (SAS®) 9.4. 
(Please refer section 6.0).  
 
  
6.0 
GENERAL CONSIDERATIONS FOR STATISTICAL ANALYSIS 
The statistical analysis will be performed using the SAS version 9.4. The descriptive 
statistics for the continuous data will be presented using mean, standard deviation, 
standard error, median and 95% CI, whereas, for the categorical data it will be 
presented using number of observations (n) and percentages (%) For continuous data, 
normality will be tested though “Kolmogorov-Smirnov Goodness-of-Fit Test”. If 
normality assumption will not fulfil then non-parametric methods such as Mann 
Whitney U/ Kruskal Wallis Test will be used.  
 
     Following statistical tests/procedure will be performed wherever required:  
 
     Clopper Pearson Method for Confidence Interval  
     The Proc Freq procedure of SAS will be used to find the 95% CI: 
ods output;  
binomial = <name of dataset containing p-value>;  
PROC FREQ data=<dataset name>;  
by <list of categorical variables>;  
tables<values of the categorical variables >/binomial alpha=<significant level>;  
weight <count>;  
exact binomial;  
run;  


 
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ods output close; 
 
     Proc mixed for MMRM ANCOVA Model 
proc mixed; 
class var1 var2; 
model var1 = var2;  
random var1 var1*var2;  
run; 
 
 
    The Proc Means procedure of SAS will be used to find the summary statistics 
     PROC means data=<dataset name>;  
                    var < variable to be analyzed >;  
     OUTPUT OUT=<name of dataset containing all statistics>  
     N=n MEAN=mean STDERR=stderr LCLM=lclm Uclm=uclm;  
     run; 
 
     Chi-square Test 
     The Proc Freq procedure of SAS will be used to find the p-value: 
ods output;  
Chi-square = <name of dataset containing p-value>;  
PROC FREQ data=<dataset name>;  
by <list of categorical variables>;  
tables<values of the categorical variables >/CHISQ=<significant level>;  
weight <count>;  
run;  
ods output close; 
 
    Fisher Test 


 
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    The Proc Freq procedure of SAS will be used to p-value: 
ods output;  
fisher = <name of dataset containing p-value>;  
PROC FREQ data=<dataset name>;  
by <list of categorical variables>;  
tables<values of the categorical variables >/fisher=<significant level>;  
weight <count>;  
 run;  
 ods output close; 
 Proc TTEST < options >;  
class variable;  
paired variables;  
by variables;  
var variables;  
 
6.0 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS 
6.1 
Demographics 
Demographic and baseline characteristics, including age, sex, race, weight, BMI, 
medical history and conditions, prior anti-psoriasis therapy, duration of disease and 
any other study-appropriate data (e.g. PASI, BSA, IGA) will be tabulated and 
summarized by treatment groups. In addition, following parameters (by both 
independent dermatologist and investigator) will be summarized by number and 
percentages: 
 Patients with PASI <20 and PASI ≥ 20.  
 Patients with IGA of 3 and IGA of 4 
 Patients with prior exposure to systemic therapy  
 Patients with prior exposure of biologics 
 


 
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6.2 
Prior and concomitant medication  
Prior and concomitant medications will be summarized by treatment group. Prior 
medications are defined as treatments taken and stopped prior to first dose of study 
treatment. Any medication given at least once between the day of first dose of 
randomized study treatment and the last day of study visit will be a concomitant 
medication, including those which were started pre-baseline and continued into the 
treatment period.  
 
All prior, concomitant and prior/ concomitant medications that were recorded on the 
CRF will be coded and summarized, according to the generic names using the WHO 
drug classification (WHODD) dated September 1, 2019 or later, using the number and 
percentage of subjects for safety population. A listing of all prior, concomitant and 
prior/ concomitant medications will also be provided. 
6.3 
Baseline and Screening Conditions 
6.3.1 Baseline Medical History 
Relevant medical history should be recorded and should include prior/current medical 
conditions, including psoriasis diagnosis, and abnormal physical exam findings or 
clinically significant laboratory abnormalities (excluding study disease-related 
abnormalities) from the baseline assessment. Medical/ surgical history will be coded 
according to the MedDRA dictionary version 22.1 or later and will be summarized 
using number (%) of subjects for safety population, corresponding subject data listing 
will also be provided. 
 
6.3.2 Other Screening Assessments  
Menstrual history of women, QuantiFERON TB-Gold test and viral serology that are 
assessed at screening only for inclusion and exclusion testing will not be presented 
separately. However, the frequency and percentage will be presented for patients who 
will be eligible to participate based on all screening conditions.  
 
7.0 
EFFICACY ANALYSES 
7.1    Primary Efficacy Analysis 
Summary statistics with 95% confidence interval will be presented for PASI. 
Comparison of percentage of patients achieving at least 75% reduction from Baseline 


 
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PASI score (PASI-75) to Week 12 between treatment arm and placebo will be 
evaluated using Chi-square/Fisher’s exact test with responder and non-responder 
psoriasis type. Also, 95% CI for the responders within treatment will be evaluated by 
using Clopper-Pearson method and 95% CI for treatment difference will be evaluated 
by using Miettinen-Nurminen method.  
 
Additional sensitivity analysis will be tested by using Cochran-Mantel-Haenszel 
(CMH) test after adjusting the sites and baseline PASI score. The analysis will be 
performed on efficacy population. No multiplicity adjustments will be done for the 
primary analysis. 
Two sets hypotheses will be tested, 
1. H0: P1=P0 vs H1: P1≠P0 
2. H0: P2=P0 vs H1: P2≠P0 
Where, P0, P1 and P2 are the proportion of responders in placebo, 400 mg and 600 mg 
arms, respectively. Since, both hypotheses will be tested separately, no multiplicity 
adjustment will be done. 
7.2      Secondary Efficacy Analysis 
 Comparison of percentage of patients achieving at least 75% reduction from 
baseline PASI (PASI-75) score at 4 and 8 weeks between test and placebo will be 
evaluated using Chi-square/ Fisher’s exact test with responder and non-responder 
psoriasis type. Also, 95% CI for treatment and for treatment difference will be 
evaluated by Clopper-Pearson method and Miettinen-Nurminen method, 
respectively. 
 Comparison of percentage of patients achieving at least 50% reduction from 
baseline PASI (PASI-50) score at 4, 8 and 12 weeks between test and placebo will 
be evaluated using Chi-square/ Fisher’s exact test with responder and non-
responder psoriasis type. Also, 95% CI for treatment and for treatment difference 
will be evaluated by Clopper-Pearson method and Miettinen-Nurminen method, 
respectively. 
 Comparison of percentage of patients with Investigator Global Assessment (IGA) 
scores of 0 or 1 at 4, 8 and 12 weeks of treatment (end of treatment) between test 
and placebo will be evaluated using Chi-Square test. Also, 95% CI for treatment 
and for treatment difference will be evaluated by Clopper-Pearson method and 
Miettinen-Nurminen method, respectively. 


 
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 Absolute and percent change of PASI score at visit 4, 8 and 12 from baseline will 
be computed using given formula: 
%Change of PASI Score for time T= (PASI score at T- PASI score at baseline) *100 
                                                           PASI score at baseline 
where time T can be week 4, week 8 and week 12. 
 
Summary statistics of absolute & percent change from baseline in PASI score at 
week 4, 8 and 12 will be presented as n, mean median, SD, SE and 95% 
confidence interval for mean. Comparison of percent change in PASI scores from 
baseline to week 4, week 8 and week 12 between treatment groups i.e., from AUR 
400mg to placebo and AUR 600mg to placebo will be analyzed using analysis of 
covariance (ANCOVA) model with baseline scores included as a covariate.  
 Summary statistics of IGA score at baseline (screening), week 4 (visit 4), week 8 
(visit 6) and week 12 (visit 7) and also respective absolute and percent change at 
week 4, week 8 and week 12 from baseline will be presented as n, mean median, 
SD, SE, and 95% confidence interval for mean. Comparison of mean change in 
IGA scores from baseline to week 4, week 8 and week 12 between treatment 
groups will be analyzed using analysis of covariance (ANCOVA) model with 
baseline scores included as a covariate.  
 Summary statistics of BSA (Body Surface Area) score at baseline (screening), 
week 4 (visit 4), week 8 (visit 6) and week 12 (visit 7) and respective absolute and 
percent change at week 4, week 8 and week 12 from baseline will be presented as 
n, mean median, SD, SE and 95% confidence Baseline interval for mean. 
Comparison of mean change in BSA scores from to week 4, week 8 and week 12 
between treatment groups will be analyzed using analysis of covariance 
(ANCOVA) model with baseline scores included as a covariate. 
 Summary statistics of DLQI score at (screening), week 4 (visit 4), week 8 (visit 6) 
and week 12 (visit 7) and absolute and percent change in DLQI score at week 4 
(visit 4), week 8 (visit 6) and week 12 (visit 7) from baseline will be presented as 
n, mean, SD, SE, median and 95% confidence interval for mean. Comparison of 
mean change in DLQI scores from baseline to week 4, week 8 and week 12 
between treatment groups will be analyzed using analysis of covariance 
(ANCOVA) model with baseline scores included as a covariate.  
For MMRM ANCOVA model, change will be taken as dependent variable and the 
baseline value, treatment, visit (main effect) and visit *treatment (interaction effect) 
will be taken as independent variables. 
 
 
Change = β0+ β1*baseline + β2*treatment+β3*visit+ β4*(visit*treatment), 
 
where Y=change from baseline in different scores and β0, β1, β3, β4=coefficients. 


 
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Title: Statistical Analysis Plan-Module I 
SOP Number: 
JSS-DM-BIS-01 
Current Version Number: 1.0 
Previous Version Number: Nil 
Document Date: 
25MAR2021 
 
 
 
Protocol No.  AUR101-201                                                       Confidential                                              
25MAR2021 
JSS-DM-BIS-01 v 11.0 – Annexure I                                                                                                                      Page 31 of 37 
                                      
First, the covariance structure will be kept as unstructured. If the model will not 
converge then autoregressive AR(1) covariance structure will be used for covariance 
matrix. 
7.3  
Additional Analysis 
 Comparison of PASI-75 and PASI-50 at week 2, 6 and 14 by Chi-square/ Fisher’s 
exact test also. Also, 95% CI for treatment and for treatment difference will be 
evaluated by Clopper-Pearson method and Miettinen-Nurminen method, 
respectively. 
 Comparison of percentage of patients achieving at least 90% reduction from 
baseline PASI (PASI-90) score at 2, 4, 6, 8, 12 and 14 weeks between test and 
placebo will be evaluated using Chi-square/ Fisher’s exact test with responder and 
non-responder psoriasis type. Also, 95% CI for treatment and for treatment 
difference will be evaluated by Clopper-Pearson method and Miettinen-Nurminen 
method, respectively. 
 Comparison of percentage of patients achieving 100% reduction from baseline 
PASI (PASI-100) score at 2, 4, 6, 8, 12 and 14 weeks between test and placebo 
will be evaluated using Chi-square/ Fisher’s exact test with responder and non-
responder psoriasis type. Also, 95% CI for treatment and for treatment difference 
will be evaluated by Clopper-Pearson method and Miettinen-Nurminen method, 
respectively. 
 IGA responder (IGA of 0 or 1) will be compared across treatment groups at week 
2, 6 and 14 by Chi-square/ Fisher’s exact test also. 
 Absolute change in IGA, percent change in PASI & BSA and absolute change in 
DLQI will also be compared across treatment groups at week 2, 6 and 14 by 
ANCOVA with baseline as covariate 
 Percentage of patients achieving MCID (≥ 5-points reduction from baseline) in 
DLQI will be compared across the treatment groups by Chi-square/ Fisher’s exact 
test at week 2, 4, 6, 8, 12 and 14 
 Percentage of patients achieving DLQI score of 0 or 1 at week 2, 4, 6, 8, 12 and 14 
will be compared across the treatment groups by Chi-square/ Fisher’s exact test 
 An analysis of combined active arms (i.e. 400 mg BID and 600 mg BID) vs. 
placebo arms will be done for PASI75, PASI90, PASI100 and IGA responders 
(i.e. IGA of 0 or 1) at week 4, 8 and 12 by Chi-square/ Fisher’s exact test. For this 
assessment, only independent dermatologist evaluation will be considered.   
 
7.4 
Subgroup Analysis 
 


 
JSS Medical Research India Private Limited   
Data Management 
 
Title: Statistical Analysis Plan-Module I 
SOP Number: 
JSS-DM-BIS-01 
Current Version Number: 1.0 
Previous Version Number: Nil 
Document Date: 
25MAR2021 
 
 
 
Protocol No.  AUR101-201                                                       Confidential                                              
25MAR2021 
JSS-DM-BIS-01 v 11.0 – Annexure I                                                                                                                      Page 32 of 37 
                                      
1. Following analysis will be repeated for subgroup of PASI <20 and PASI≥ 20 and 
IGA of 3 and IGA of 4: 
 
 PASI-50, PASI-75, PASI-90 and PASI-100 responder (as per independent 
dermatologist assessment only) comparison at week 4, 8, and 12 by Chi-
square/ Fisher’s exact test 
 Change in PASI score (as per independent dermatologist assessment only)  at 
week 4, 8 and 12 from baseline will assessed by ANCOVA with baseline as 
covariate. 
 IGA responder (IGA of 0 or 1; as per independent dermatologist assessment 
only) comparison by week 4, 8 and 12 by Chi-square/ Fisher’s exact test 
 IGA reduction (as per independent dermatologist assessment only) analysis by 
week 4, 8 and 12 i.e. proportion of the patients with at least 1-point reduction, 
2-points reduction, 3-points reduction and 4-points reduction (Only for 
baseline IGA of 4) 
 
2. Patient with Head & neck PASI of 12 
 PASI-50, PASI-75, PASI-90 and PASI-100 responder (as per independent 
dermatologist assessment only) comparison at week 4, 8, and 12 by Chi-
square/ Fisher’s exact test 
7.5      Pharmacokinetic (PK) Analysis 
PK analysis will be performed on PK population. 
Individual plasma PK parameters, including area under the concentration-time curve 
(AUC0-12), terminal elimination half-life (t1/2), maximum plasma concentration (Cmax), 
time to reach maximum plasma concentration (Tmax), elimination rate constant (Kel ) 
and clearance (Cl) will be summarized and presented as described for continuous 
variables. Along with mean, SD, median and geometric mean concentration (GMC) 
and 95% GMC will also be provided by treatment arms. 
Pharmacokinetic analysis will be performed only of sufficient patient’s data are 
available.  
8.0     SAFETY & TOLERABILITY ASSESSMENT ANALYSIS 
 
The analysis of safety assessments in this study will include summaries of the 
 
following categories of safety data collected for each subject  
 
Adverse Events 
  
Physical Examination  


 
JSS Medical Research India Private Limited   
Data Management 
 
Title: Statistical Analysis Plan-Module I 
SOP Number: 
JSS-DM-BIS-01 
Current Version Number: 1.0 
Previous Version Number: Nil 
Document Date: 
25MAR2021 
 
 
 
Protocol No.  AUR101-201                                                       Confidential                                              
25MAR2021 
JSS-DM-BIS-01 v 11.0 – Annexure I                                                                                                                      Page 33 of 37 
                                      
  
Vital Sign 
  
ECG Record 
  
Laboratory Test 
 
Treatment emergent adverse events (AEs) and serious adverse events (SAEs) will be 
reported by frequency analysis with respect to incidence, severity as well as 
seriousness. Clinically significant alterations in clinical laboratory parameters, vital 
signs and ECG will be reported.  
All safety parameters (e.g. AEs, physical examination, vital signs, ECG parameters, 
Laboratory evaluations) will be summarized descriptively and by treatment. 
Continuous variables will be described by number (n) of non-missing observations, 
arithmetic mean, standard deviation, standard error, median and 95%CI. Categorical 
variables will be described by frequency tables (counts and percentages), however in 
case of very low occurrences instead of tables with zero proportions, note statement 
will be added in respective section of table. Safety evaluations will be done on safety 
population. No formal statistical testing will be performed on the safety data.   
8.1 
Adverse Events 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA).  
The number and percentages of patients experiencing AEs will be tabulated by system 
organ class (SOC), preferred term, maximum severity, and relationship to AUR101. 
Summaries of the number of patients with DLTs, dose reductions/interruptions, SAEs, 
treatment-related AEs, AEs resulting in treatment/trial discontinuation, and deaths will 
be presented by dose cohort. 
 
8.2 
Physical Examination 
The baseline medical history of subjects includes information regarding physical 
history for different body systems (General Appearance, Skin, Neck, Eyes, Lungs 
etc.). Weight will be recorded at every visit except visit 3, 5 and follow up visit. 
Height will be captured at screening only. Change in weight and BMI from baseline 
will be calculated and descriptive statistics (Mean, SD, SE, median) will be presented 
in dose-wise groups. For rest of the physical examination data, a listing will be 
presented 
8.3       Vital Signs  


 
JSS Medical Research India Private Limited   
Data Management 
 
Title: Statistical Analysis Plan-Module I 
SOP Number: 
JSS-DM-BIS-01 
Current Version Number: 1.0 
Previous Version Number: Nil 
Document Date: 
25MAR2021 
 
 
 
Protocol No.  AUR101-201                                                       Confidential                                              
25MAR2021 
JSS-DM-BIS-01 v 11.0 – Annexure I                                                                                                                      Page 34 of 37 
                                      
Standard vital signs will include the blood pressure, pulse rate, respiratory rate, and 
body temperature. Vital signs at each visit and the change from baseline to each post-
baseline assessment will be summarized using descriptive statistics.  
These parameters will be analyzed using number (n) of non-missing observations, 
mean, standard deviation (SD), SE, median and 95%CI.  Change from baseline in vital 
sign parameters will also be reported. 
8.4 
ECG  
Overall interpretation of 12 lead ECG will contain within normal limits, abnormal but 
not clinically significant, or abnormal and clinically significant categories. 
The ECG data will be analyzed by treatment groups at each visit using frequency 
count and percentage of subjects by treatment groups.  
8.5       Laboratory Parameters 
The laboratory parameters will include Hematology, Liver function Test, and Renal 
Function Test samples by visits. 
The categorical variables will be analyzed using frequency count and percentage of 
subjects, and continuous variables will be analyzed using number (n) of non-missing 
observations, mean, standard deviation, SE and median (IQR) by groups. Any change 
from baseline in laboratory parameters in terms of normal or abnormal (clinically 
significant or not significant) findings will also be reported through shift tables for 
overall data without mentioning the groups. Descriptive statistics (Mean, median, SD, 
SE and 95% CI) will be presented for change from baseline to the respective visit.  
8.6      Urine Pregnancy Test 
For Urine Pregnancy Test listing will be provided.   
9.0 
REPORTING CONVENTIONS 
9.1 
Reporting of Numeric Values 
 All data will be presented by treatment group. Where appropriate, data will be 
presented including a total overall column and by visit in addition to treatment 
group. 


 
JSS Medical Research India Private Limited   
Data Management 
 
Title: Statistical Analysis Plan-Module I 
SOP Number: 
JSS-DM-BIS-01 
Current Version Number: 1.0 
Previous Version Number: Nil 
Document Date: 
25MAR2021 
 
 
 
Protocol No.  AUR101-201                                                       Confidential                                              
25MAR2021 
JSS-DM-BIS-01 v 11.0 – Annexure I                                                                                                                      Page 35 of 37 
                                      
 Summary descriptive statistics will consist of the number and percentage of 
responses in each category for discrete variables, and the mean, median, standard 
deviation (SD), SE, median and 95% confidence interval for continuous variables.  
 Mean and Median values will be reported to one decimal place. Standard 
deviation, standard error and 95% confidence interval values will be reported to 
two decimal places.  
 Percentages will be rounded to one decimal place. Where appropriate, the number 
and percentage of responses will be presented in the form XX (XX.X %). 
 All Adverse Events (AE) and Serious Adverse Events (SAE) will be presented: 
Number of events, Number of subjects and %(n/N) of subjects. 
 P-values will be rounded to three decimal places. P-values less than 0.001 will be 
reported as <0.001 in tables. P-values greater than 0.999 will be reported as 
>0.999.  
 P value <0.05 will be considered significant. 
 All listings will be sorted for presentation in order of site number, patient number, 
date of procedure or event.  
 All categories of variables will be presented even if there is no data. Zero       
frequencies are going to be represented as “0 (0.0%) “in reporting of results.  
10.0 OUTPUT 
(TABLES, 
LISTINGS 
AND 
GRAPHS) 
CONSIDERATIONS  
 
The default Tables, Listings and Graphs (TLG) layout will be as follows. 
Orientation 
All pages should preferably be landscape. 
Paper Size 
Legal size 
Margins 
Top: 1 in 
Bottom: 0.75 in 
Left: 0.75 in 
Right: 0.75 in 
Font 
Font style (preferably Times New Roman) of the Text 


 
JSS Medical Research India Private Limited   
Data Management 
 
Title: Statistical Analysis Plan-Module I 
SOP Number: 
JSS-DM-BIS-01 
Current Version Number: 1.0 
Previous Version Number: Nil 
Document Date: 
25MAR2021 
 
 
 
Protocol No.  AUR101-201                                                       Confidential                                              
25MAR2021 
JSS-DM-BIS-01 v 11.0 – Annexure I                                                                                                                      Page 36 of 37 
                                      
Headers 
Titles of Table/Listing will be center 
Left  
Sponsor: 
Study Name: 
Protocol No:  
Footers 
Left  
Analyst Initials:  
Program Name: 
Program Run date: time:  
Right  
Datasets Used: 
Page XXX of YYY 
The margin may be reduced as necessary to allow additional rows to be presented, but not at the expense of 
clarity. In addition, the orientation may be changed to portrait if appropriate. The date format for all 
presentations will be ‘DDMMMYYYY’. 
11.0 
REFERENCES 
 
1. Lubberts E. The IL-23-IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol. 2015; 11:562. 
2. Gaffen SL, Jain R, Garg AV, Cua DJ. The IL-23-IL-17 immune axis: from mechanisms to therapeutic 
testing. Nat Rev Immunol. 2014; 14:585–600. 
3. Marta Catarina Esteves Guedes, Luis Miguel Borrego, and Rui Daniel Proença. Roles of interleukin-17 in 
uveitis. Indian J Ophthalmol. 2016 Sep;64(9):628–34. 
4. Ruan Q, Kameswaran V, Zhang Y, Zheng S, Sun J, Wang J, et al. The Th17 immune response is controlled 
by the Rel-RORgamma-RORgamma T transcriptional axis. J Exp Med. 2011;208(11):2321–33. 
5. Khilji FA, Gonzalez M, Finlay AY. Clinical meaning of change in dermatology life quality index scores 
[abstract P-59]. Br J Dermatol 2002; 147 (suppl 62): 50. 
6. 13 Basra MK, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the minimal clinically important 
difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology 
2015; 230: 27–33. 
7. Khilji FA, Gonzalez M, Finlay AY. Clinical meaning of change in dermatology life quality index scores 
[abstract P-59]. Br J Dermatol 2002; 147 (suppl 62): 50. 
8. 13 Basra MK, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the minimal clinically important 
difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology 
2015; 230: 27–33. 
9. Aurigene 101-201 Protocol, 7 Aug 2019, Version 1.0 
10. Aurigene CRF v3.0_30.1.2020 
11. ICH E3: Structure and content of Clinical Study Reports, November 1995, CPMP 
12. ICH E9: Statistical Principles for Clinical Trials, September 1998, CP 


 
JSS Medical Research India Private Limited   
Data Management 
 
Title: Statistical Analysis Plan-Module I 
SOP Number: 
JSS-DM-BIS-01 
Current Version Number: 1.0 
Previous Version Number: Nil 
Document Date: 
25MAR2021 
 
 
 
Protocol No.  AUR101-201                                                       Confidential                                              
25MAR2021 
JSS-DM-BIS-01 v 11.0 – Annexure I                                                                                                                      Page 37 of 37