Conditions: Plaque Psoriasis Skin Diseases
Keywords: JTE-051 Psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 13
Healthy volunteers: no

Brief summary:
Study to evaluate the efficacy, safety, tolerability and pharmacokinetics of JTE-051 administered for 12 weeks in subjects with moderate to severe plaque psoriasis.

Detailed description:

Arms:
arm 1: One dose of study drug by mouth daily for 12 weeks arm 2: One dose of study drug by mouth daily for 12 weeks arm 3: One dose of study drug by mouth daily for 12 weeks arm 4: One dose of study drug by mouth daily for 12 weeks arm 5: One dose of study drug by mouth daily for 12 weeks

Interventions: intervention 1: JTE-051 intervention 2: Placebo
Intervention descriptions: intervention 1: Active drug tablets containing JTE-051 intervention 2: Placebo tablets identical in appearance to the active drug tablets

Protocol document:
Prot_000.pdf: 
 
ClinicalTrials.gov Posted Document Cover Page 
Clinical Study Protocol 
 
PROTOCOL TITLE:  
A Multicenter, Randomized, Double-blind, PlaCebo-controlled, 
Parallel-group Study to EvaLuate the Safety and Efficacy of 
JTE-051 Administered for 12 Weeks in Subjects with ModeRate 
to Severe Plaque PSoriasis (CLEAR-PS) 
PROTOCOL NUMBER: AE051-G-16-007 
PROTOCOL DATE:  
8 October 2018 
NCT NUMBER: 
NCT03358290 
 
 
 


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Cover Page 
Akros Pharma Inc. 
Clinical Study Protocol  
PROTOCOL TITLE: 
A Multicenter, Randomized, Double-blind, PlaCebo-controlled, 
Parallel-group Study to EvaLuate the Safety and Efficacy of 
JTE-051 Administered for 12 Weeks in Subjects with 
ModeRate to Severe Plaque PSoriasis (CLEAR-PS) 
 
PROTOCOL NUMBER: 
AE051-G-16-007 
 
DATE: 
8 October 2018 
 
IND NUMBER:  
 
 
EUDRACT NUMBER 
2018-003209-24 
 
SPONSOR: 
Akros Pharma Inc.  
302 Carnegie Center, Suite 300 
Princeton, NJ  08540 
 
SPONSOR CONTACT: 
  
Akros Pharma Inc. 
  
 
MEDICAL MONITOR: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confidentiality Statement 
The confidential information in this document is provided to you as an Investigator or consultant for review by you, your staff 
and the applicable Institutional Review Board/Independent Ethics Committee (IRB/IEC). Your acceptance of this document 
constitutes agreement that you will not disclose the information contained herein to others or use the information for any 
purpose other than the performance of your obligations pursuant to your and/or your employer’s separate agreement with us, 
our affiliate or our contractor, as the case may be, without prior written authorization from Akros Pharma Inc. (Akros). 




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Table of Contents 
Cover Page................................................................................................................................ 1 
Signature Page ......................................................................................................................... 2 
Table of Contents ..................................................................................................................... 3 
List of Abbreviations and Definition of Terms ....................................................................... 6 
Protocol Synopsis ..................................................................................................................... 9 
1 
Introduction .................................................................................................................... 13 
1.1 
Background ........................................................................................................... 13 
1.1.1 Psoriasis .............................................................................................................. 13 
1.1.2 Treatment of Psoriasis......................................................................................... 13 
1.1.3 Interleukin-2-inducible T-cell Kinase ................................................................. 14 
 
1.2 
JTE­051 .................................................................................................................. 15 
1.2.1 Nonclinical Studies ............................................................................................. 15 
1.2.2 Clinical Information ............................................................................................ 20 
1.3 
Justification of Study Population and Dose Selection ....................................... 24 
1.3.1 Justification for Study Population ....................................................................... 24 
1.3.2 Justification for Study Design ............................................................................. 25 
1.3.3 Justification for Dose Selection .......................................................................... 25 
2 
Study Objectives ............................................................................................................. 27 
3 
Investigational Plan ....................................................................................................... 27 
3.1 
Number of Sites and Subjects .............................................................................. 27 
3.2 
Study Design .......................................................................................................... 27 
3.3 
Selection of Study Population .............................................................................. 27 
3.3.1 Inclusion Criteria ................................................................................................ 27 
3.3.2 Exclusion Criteria ............................................................................................... 29 
3.4 
Removal of Subjects from the Study ................................................................... 32 
3.5 
Study Procedures .................................................................................................. 34 
3.5.1 Screening Period ................................................................................................. 38 
3.5.2 Double-blind Treatment Period .......................................................................... 38 
3.5.3 Follow-up Period ................................................................................................ 39 
3.5.4 Study Restrictions ............................................................................................... 40 
3
 
3.5.6 Procedure Definitions ......................................................................................... 46 
3.6 
Adverse Events ...................................................................................................... 57 
3.6.1 Safety Definitions ............................................................................................... 57 


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3.6.2 Assessing Adverse Events .................................................................................. 58 
3.6.3 Reporting Adverse Events .................................................................................. 60 
3.7 
Identification of Treatments ................................................................................ 61 
3.7.1 Method of Assigning Subjects to Treatment Groups .......................................... 61 
3.7.2 Identity of Investigational Products .................................................................... 61 
3.7.3 Storage and Handling Procedures ....................................................................... 62 
3.7.4 Clinical Supplies Packaging ............................................................................... 62 
3.7.5 Administration of Study Drug ............................................................................ 62 
3.7.6 Management of Clinical Supplies ....................................................................... 63 
3.7.7 Randomization .................................................................................................... 63 
3.7.8 Blinding............................................................................................................... 64 
3.7.9 Breaking the Blind .............................................................................................. 64 
3.8 
Statistical Methods ................................................................................................ 64 
3.8.1 Subject Population for Analysis.......................................................................... 64 
3.8.2 Interim Analysis .................................................................................................. 67 
3.8.3 Efficacy Analyses ............................................................................................... 68 
3.8.4 Safety Analyses ................................................................................................... 71 
3.8.5 Pharmacokinetic Analyses .................................................................................. 71 
3.9 
Quality Control and Quality Assurance ............................................................. 72 
4 
Investigator Obligations ................................................................................................. 72 
4.1 
Institutional Review/Independent Ethics Committee ........................................ 72 
4.2 
Subject Consent ..................................................................................................... 73 
4.3 
Data Collection ...................................................................................................... 74 
4.3.1 Case Report Forms .............................................................................................. 74 
4.3.2 Source Documents .............................................................................................. 74 
4.4 
Adherence to Protocol .......................................................................................... 74 
4.5 
Reporting Adverse Events .................................................................................... 74 
4.6 
Investigator’s Final Report .................................................................................. 74 
4.7 
Records Retention ................................................................................................. 74 
4.8 
Confidentiality ....................................................................................................... 75 
4.9 
Publications ........................................................................................................... 75 
5 
Study Management ........................................................................................................ 76 
5.1 
Monitoring ............................................................................................................. 76 
5.2 
Management of Protocol Amendments and Deviations .................................... 76 
5.3 
Study Termination ................................................................................................ 77 
5.4 
Sponsor’s Final Report ......................................................................................... 77 
6 
References ...................................................................................................................... 78 


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List of Figures 
 
Figure 1. 
Planned Study Schema ........................................................................................ 34 
Figure 2. 
Dosing and Pharmacokinetic Sample Collection Time ...................................... 37 
 
 
List of Tables 
 
Table 1. 
Planned Schedule of Study Procedures ............................................................... 35 
Table 2. 
Psoriasis Therapy Restrictions ............................................................................ 40 
Table 3. 
Other Medications Restrictions........................................................................... 41 
1 
 
 
Table 7. 
The PASI Scoring ............................................................................................... 48 
Table 8. 
PASI 75 Response Rate Used in Simulation ...................................................... 66 
Table 9. 
The Marginal Distribution of the Decision ......................................................... 67 
Table 10. 
The Conditional Go Probability Assuming a Monotone Dose Response ........... 67 
 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition of term 
Ab 
Antibody 
ADAMTSL5 
A 
disintegrin-like 
and 
metalloprotease 
domain 
containing 
thrombospondin type 1 motif-like 5 
AE 
Adverse event 
AI-NRS 
Average-Itch Numeric Rating Scale 
ALB 
Albumin 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve 
AUC0-inf 
Area under concentration time curve from the time of dosing to infinity 
AUC0-24 
Area under the concentration-time curve from the time of dosing until 
the 24 hour time point 
BCRP 
Breast cancer resistance protein 
BMI 
Body mass index 
BSA 
Body surface area 
BUN 
Blood urea nitrogen 
Caco-2 cells 
Human colonic adenocarcinoma cells 
CAIA 
Collagen antibody-induced arthritis 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
Cmax 
Maximum concentration 
CPK 
Creatinine phosphokinase 
CRF 
Case report form 
CRN 
Creatinine 
CRP 
C-reactive protein 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
Cytochrome P450 
DDI 
Drug-drug interaction 
ECG 
Electrocardiogram 
EOT 
End of treatment 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practices 
GGT 
Gamma­glutamyl transferase 
GI 
Gastrointestinal 
GLP 
Good laboratory practice 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 


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Abbreviation 
Definition of term 
Hct 
Hematocrit 
HCV 
Hepatitis C virus 
HDL 
High density lipoprotein 
HEENT 
Head, ears, eyes, nose, throat 
HEK 
Human embryonic kidney 
hERG 
Human ether-a-go-go-related gene 
Hgb 
Hemoglobin 
HIV 
Human immunodeficiency virus 
hs-CRP 
High sensitivity C-reactive protein 
IB 
Investigator’s brochure 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IFNγ 
Interferon γ 
IL 
Interleukin 
IL-1β 
Interleukin-1β 
IL-2 
Interleukin-2 
IL-6 
Interleukin-6 
IL-17 
Interleukin-17 
IL-23 
Interleukin-23 
IMP 
Investigational medicinal product 
IND 
Investigational new drug application 
IRB 
Institutional Review Board 
ITK 
Interleukin-2-inducible T cell kinase 
ITT 
Intent-to-treat population 
IV 
Intravenous 
IWRS 
Interactive Web Response System 
LC-MS/MS 
Liquid chromatography/tandem mass spectrometry 
LCL 
Lower confidence level 
LDH 
Lactate dehydrogenase 
LOCF 
Last observation carried forward 
LRV 
Lower reference value 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOA 
Mechanism of action 
mRNA 
Messenger ribonucleic acid 
MTD 
Maximum tolerated dose 
MTX 
Methotrexate 
N/A 
Not applicable 
NOAEL 
No observed adverse effect level 
NSAID 
Non-steroidal anti-inflammatory drug 


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Abbreviation 
Definition of term 
OAT 
Organic anion transporter 
OATP 
Organic anion transporting polypeptide 
OCT 
Organic cation transporter 
OECD 
Organization for Economic Co-operation and Development 
PASI 
Psoriasis area and severity index 
P-gp 
P-glycoprotein 
pH 
Logarithmic measure of hydrogen ion concentration 
PI 
Principal Investigator 
PK 
Pharmacokinetic(s) 
PP 
Per protocol 
PR 
Interval from beginning of the P wave to the beginning of the QRS 
complex in the frontal plane 
PT 
Prothrombin time 
QD 
Once daily 
QOL 
Quality of life 
QTcF 
Fridericia-corrected QT Interval 
RA 
Rheumatoid arthritis 
 
RR 
Interval from beginning of the QRS complex in the frontal plane to the 
next QRS complex 
SAE 
Serious adverse event(s) 
SAP 
Statistical analysis plan 
SAS 
Statistical analysis system 
SD 
Standard deviation 
Skindex-16 
A 16-item, skin-related quality of life questionnaire 
SOC 
System organ class(es) 
SPF 
Sun protection factor 
sPGA 
Static Physician’s Global Assessment 
SUSAR 
Suspected unexpected serious adverse reaction 
TB 
Tubercle bacillus 
TCR 
T cell receptor 
TEAE 
Treatment-emergent adverse event 
TG 
Triglycerides 
TNSn 
Total neuropathy score nurse 
Treg 
Regulatory T cells 
 
TSH 
Thyroid stimulating hormone 
TV 
Target value 
UCL 
Upper confidence level 
WI-NRS 
Worst-Itch Numeric Rating Scale 


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Protocol Synopsis 
STUDY TITLE 
A Multicenter, Randomized, Double-blind, PlaCebo-controlled, 
Parallel-group Study to EvaLuate the Safety and Efficacy of 
JTE-051 Administered for 12 Weeks in Subjects with ModeRate 
to Severe Plaque PSoriasis (CLEAR-PS) 
PROTOCOL NUMBER AE051-G-16-007 
CLINICAL PHASE 
Phase 2a 
STUDY DURATION 
Approximately 20 weeks duration per subject: 
• Up to 28-day Screening Period 
• 12-week double-blind Treatment Period 
• 4-week Follow-up Period 
STUDY OBJECTIVES 
• To evaluate the efficacy of JTE-051 administered for 
12 weeks in subjects with moderate to severe plaque 
psoriasis. 
• To evaluate the safety and tolerability of JTE-051 
administered for 12 weeks in subjects with moderate to severe 
plaque psoriasis. 
• To evaluate the pharmacokinetics (PK) of JTE-051 
administered for 12 weeks in subjects with moderate to severe 
plaque psoriasis. 
STUDY DESIGN 
This is a 12-week, multicenter, randomized, double-blind, 
placebo-controlled, parallel-group study in subjects with 
moderate to severe plaque psoriasis. Eligible subjects will be 
randomized at Visit 2 to receive JTE-051 50 mg, 100 mg, 
150 mg, 200 mg or placebo once daily (QD) for 12 weeks. 
Approximately 85 subjects are planned to be randomized into 
5 treatment groups. A follow-up visit will take place 
approximately 4 weeks after the last dose of study drug. 
Randomization will be stratified based on prior exposure of 
subjects to biologic therapy (i.e., biologic treatment-naïve vs. 
biologic treatment-experienced subjects). 
PLANNED NUMBER 
OF SUBJECTS TO BE 
ENROLLED AND 
RANDOMIZED 
A sufficient number of subjects will be screened to ensure the 
randomization (in a 1:1:1:1:1 ratio) of approximately 85 subjects 
(17 subjects in each treatment group). 


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KEY ELIGIBILITY 
CRITERIA 
• Male or female, 18 to 70 years of age (inclusive) at Visit 1 
(Screening Visit) and diagnosed with moderate to severe 
plaque psoriasis at least 6 months prior to Visit 1; 
• No medical history of treatment failure to any systemic agents 
for plaque psoriasis; 
• Plaque-type psoriasis covering ≥10% of body surface area 
(BSA) at Visit 1 and Visit 2 (Baseline); 
• Psoriasis Area and Severity Index (PASI) score ≥12 at Visit 1 
and Visit 2; 
• Static Physician’s Global Assessment (sPGA) score ≥3 at 
Visit 1 and Visit 2; 
• Body Mass Index (BMI) ≤40 kg/m2 at Visit 1; 
• Negative QuantiFERON®-TB Gold test or PPD test, negative 
chest radiographic findings for tubercle bacillus (TB) and no 
other evidence of active or latent TB; 
• No history of a clinically-significant infection (e.g., that 
required oral antimicrobial therapy) within 8 weeks prior to 
Visit 2; 
• No history of infections requiring hospitalization or parenteral 
antibiotic, antiviral, antifungal or antiparasitic therapy within 
6 months prior to Visit 2 and no history of recurrent infections 
or 
conditions 
predisposing 
to 
chronic 
infections 
(e.g., bronchiectasis, chronic osteomyelitis); 
 
 
 
 
 


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INVESTIGATIONAL 
PRODUCT 
(STUDY DRUG), 
FORMULATION, 
DOSAGE,  
ROUTE AND TIME 
OF 
ADMINISTRATION 
 
JTE-051 
 
50 mg tablets 
50 mg, 100 mg, 150 mg and 200 mg 
Oral administration for 12 weeks starting on the day of 
randomization at Visit 2, QD in the morning, regardless of 
meals. On study visit days, subjects should take their scheduled 
study treatment at the clinical research site (site) under the 
supervision of the investigator or designee after all study-related 
procedures have been completed (except at Visit 6, when no 
study drug will be administered). 
REFERENCE 
PRODUCT 
(STUDY DRUG), 
FORMULATION, 
DOSAGE, 
ROUTE AND TIME 
OF 
ADMINISTRATION 
 
Placebo 
 
Tablets (identical in appearance to JTE-051 tablets)  
Not applicable (N/A) 
Oral administration for 12 weeks starting on the day of 
randomization at Visit 2, QD in the morning, regardless of 
meals. On study visit days, subjects should take their scheduled 
study treatment at the site under the supervision of the 
investigator or designee after all study-related procedures have 
been completed (except at Visit 6, when no study drug will be 
administered). 


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EVALUATION 
CRITERIA 
Primary Efficacy Parameters 
• Proportion 
of 
subjects 
achieving 
a 
minimum 
75% 
improvement from baseline in the PASI (PASI 75) at end of 
treatment (EOT). 
Secondary Efficacy Parameters 
The following will be collected at Weeks 2, 4, 8, 12 and 16 unless 
otherwise stated:  
• Percent change from baseline in PASI score; 
• Proportions of subjects achieving PASI 50, PASI 75, PASI 90 
and PASI 100; 
• Proportion of subjects achieving a sPGA score of 0 or 1; 
• Change from baseline in sPGA score; 
• Percent change from baseline in the psoriasis affected BSA; 
• Change from baseline in the Skindex-16 (a 16-item, 
skin­related quality of life questionnaire). 
 
 
 
Safety Assessments 
• 
Number and proportion of subjects with adverse events 
(AEs), type and severity of AEs, change from baseline in the 
safety laboratory, vital sign and electrocardiogram (ECG) 
parameters. 
Pharmacokinetic Assessments 
• Trough plasma levels of JTE-051; 
• Relationship between the JTE-051 dose (exposure) and 
response may be assessed (exploratory). 
STATISTICAL 
METHODS 
Appropriate statistical analysis will be performed using SAS for 
Windows® (SAS Institute Inc., Cary, NC 27512-8000, USA). 


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1 INTRODUCTION 
1.1 Background 
1.1.1 Psoriasis 
Plaque psoriasis is the most common form of psoriasis. It is a mild to severe inflammatory 
autoimmune 
disease 
with 
primary 
skin 
manifestation 
characterized 
by 
raised, 
well-demarcated, itchy erythematous circular-to-oval plaques covered with adherent silvery 
white scales. In addition to the skin-related manifestation, concomitant with psoriatic arthritis 
and nail psoriasis may be experienced by some patients. Also, it is reported patients consider 
itch to be the most bothersome symptom of psoriasis and is more likely to cause absence 
from work and reduced work productivity than psoriasis related pain or scaling.1 The number 
of patients with psoriasis is estimated to be approximately 7.5 million in the US, 7.5 million 
in the EU, 420 thousand in Japan and the worldwide prevalence of psoriasis is calculated to 
be 0.6 to 4.8%.2-5 It is also known that the quality of life (QOL) of the psoriasis patients is 
lower than that of patients with cancer or diabetes.6 As a result, psoriasis markedly restricts 
the social activities of patients. 
Psoriasis is triggered by the cells and molecules of both, innate and adaptive immune systems. 
The inflammatory cells infiltration consists mainly of dendritic cells, macrophages and 
T cells in dermis, and T cells and neutrophils in epidermis. These cells are activated through 
antimicrobial peptide such as β-defensins and auto-antigens including LL-37 and a 
disintegrin-like and metalloprotease domain containing thrombospondin type 1 motif-like 5 
(ADAMTSL5).7,8 Various cytokines produced by these immune cells play a crucial role in 
the development of psoriasis. Clinical studies of biologics targeting cytokines have revealed 
that Interleukin (IL)-17 and IL-23 play highly important roles in the disease progression and 
exacerbation of psoriasis.9-12 
A 
 
 
1.1.2 Treatment of Psoriasis 
The goal of psoriasis treatment is to achieve rapid remission induction, long-term control of 
skin manifestations and improve the QOL. The current pharmacotherapy for psoriasis mainly 
consists of topical vitamin D3 analogues and topical corticosteroids, and systemic treatments 
such as cyclosporine and methotrexate (MTX) may be used depending on the symptoms. For 
patients with concomitant psoriatic arthritis and those who have not sufficiently responded to 
conventional systemic treatments, biologics targeting tumor necrosis factor-ɑ (TNF-ɑ), IL-23, 
IL-17, etc. may be used. Cyclosporine and MTX, which form the core of the systemic 
treatment, exert their actions more rapidly and effectively compared with the topical drugs, 
and can induce remission in some patients.14 However, these drugs raise many safety 
concerns: long-term treatment with cyclosporine may cause nephropathy or increase the 
blood pressure and MTX may lead to myelosuppression and a wide variety of other side 
effects. Biologic therapies can achieve remission in many patients, making a huge 
contribution to the advances in psoriasis treatment. However, there are concerns related to 
biologics, which have yet to be addressed: (1) inadequate response to therapy in 
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(3) high financial burden (4) lack of availability of long-term safety data for these 
compounds (5) hypersensitivity reactions, such as infusion reaction, injection site reaction 
and (6) generation of neutralizing antibodies.15,16 Based on these considerations, the next 
generation therapies for psoriasis are expected to be represented by cost-effective, 
highly-efficacious and safe oral drugs that can induce remission rapidly and achieve 
complete remission with high probability. Unlike the existing drugs for systemic treatment 
that are indicated only for severe cases, cost, as well as the safety profile of the new 
generation therapeutics must allow prescribing those to any patient regardless of the severity 
of the disease. 
1.1.3 Interleukin-2-inducible T-cell Kinase 
Interleukin-2-inducible T-cell kinase (ITK) is a non-receptor protein tyrosine kinase that is 
mainly expressed in T cells, mast cells, and natural killer cells. In the T cells, the molecule 
plays a role in transmitting stimulation triggered by the antigen via the T cell receptor (TCR) 
located on the cell membrane.17 When antigen is presented with the major histocompatibility 
complex on the antigen-presenting cells such as dendritic cells and macrophages, T cells are 
activated by recognizing the antigen via the TCR. As a result of activation, T cells produce 
cytokines such as interleukin-2 (IL-2), interleukin-17 (IL-17) and interferon γ (IFNγ) and 
accelerate their own proliferation. It is also considered that T cells are significantly involved 
in the development of tissue inflammation and damage by activation of other inflammatory 
cells by these cytokines. Findings that indicate a relationship between ITK and pathological 
changes have been reported. T cells obtained from ITK­knockout mice could not show IL-2 
production in response to stimulation mimicking antigen presentation, which led to decreased 
cell proliferation. Cell proliferation is also less sensitive in the mixed lymphocyte reaction if 
obtained from mice of a different strain.18 Furthermore, it has been reported that 
ITK-knockout mice show impaired response in allergic airway inflammation induced by the 
antigen: the production of various cytokines in the T cells in lymphoid tissues, the infiltrative 
inflammatory cell counts in the airway, and the secretion of airway mucus.19 This 
information suggests that ITK may be involved in the development of pathological changes 
in autoimmune diseases, transplant rejection and allergic diseases of which the onset and 
exacerbation are caused by an excessive immune response to the antigen. 


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1.2 JTE-051 
 
 
A brief summary of the nonclinical findings to date is included below. Additional details are 
described in the JTE-051 Investigator’s Brochure (IB). 
1.2.1 Nonclinical Studies 


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1.2.2 Clinical Information 


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e 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1.3 Justification of Study Population and Dose Selection 
1.3.1 Justification for Study Population 
Subjects with moderate to severe plaque psoriasis, based on the extent of psoriasis severity 
criteria (i.e., BSA, PASI and sPGA) described in Section 3.3.1 will be enrolled in this study. 
Subjects with other types of psoriasis will be excluded from the study to ensure a 
homogenous study population. Furthermore, to minimize potential confounders in the 
efficacy response, subjects must have no history of treatment failure following any systemic 
treatment. 
From a safety perspective, study restrictions will be implemented based on the m
 of 
 
 nonclinical and clinical 
data available to date. These include restrictions aiming to minimize the risk to the 
participating subjects, to minimize the confounding factors in the assessment process and to 
monitor and adequately manage any safety-related findings. Thus, subjects at high risk of 
developing immunosuppression-related AEs, such as infections or malignancies, including 
those with pre-existing conditions (e.g., clinically-manifested or latent TB, active infections 
with HBV, HCV or HIV) or significant hematological condition are excluded from 
participating in the study. 
A 
a 
t 


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. Other, general 
safety-related restrictions, such as cardiovascular-system-related, hepatic and renal 
function-related restrictions, as well as the known safety signals associated with other 
compounds with similar mechanism of action on the market or in development, have been 
implemented. 
1.3.2 Justification for Study Design 
A parallel group, placebo-controlled design will be employed in this study, to assess the 
effect of JTE-051 on the efficacy parameters and to evaluate the safety of JTE-051, 
compared to placebo in subjects with plaque psoriasis. Briefly, upon completion of all 
protocol-mandated screening procedures, the qualified subjects will be randomized at Visit 2 
in a 1:1:1:1:1 ratio to one of the following five parallel dose groups: JTE-051 50 mg QD, 
JTE-051 100 mg QD, JTE-051 150 mg QD, JTE-051 200 mg QD or placebo QD (17 subjects 
to be randomized per arm; see Section 3.8.1.6 for considerations related to sample size 
calculation), and will receive the double-blind treatment for 12 weeks followed by a 4-week 
Follow-up Period. The single ascending dose study (AE051-U-11-001) data demonstrated no 
food effect on the PK of JTE-051; thus, study drug will be administered regardless of meals; 
nonetheless, based on the PK characteristics of the compound, the protocol requires the study 
drug administration in the morning to ensure an approximately 24-hour period between 
dosing, (see Section 1.2.2). The duration of the double-blind treatment period is sufficient to 
obtain proof-of-efficacy in subjects with plaque psoriasis, as an initial step in development. 
The duration of the Follow-up Period is set to approximately 4 weeks, standard duration for 
similar out-patient studies administered an investigational product. Based on the PK 
characteristics of JTE-051 (see Section 1.2.1), this period is considered conservative, 
 
. 
The efficacy parameters assessed in this study are consistent with the standards in the 
industry in similar psoriasis trials; appropriate efficacy analyses are planned, as detailed in 
Section 3.8.3.2. To minimize the chances of errors, all calculations of derived parameters will 
be done by the Sponsor based on the appropriate core data points collected and documented 
by the Investigators.  
With respect to safety, adequate procedures have been implemented to minimize the risks to 
the study subjects (based on the compound’s MOA and the nonclinical and clinical data 
available to date [see Sections 1.2.1, 1.2.2 for summary information and the IB for detailed 
information]) and to facilitate further characterization of the safety profile of JTE-051.  
1.3.3 Justification for Dose Selection 
The selection of JTE-051 doses in this study is based on the collective data from nonclinical 
pharmacology/toxicology studies and Phase 1 clinical studies.  
 
 
 
 


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2 STUDY OBJECTIVES 
• To evaluate the efficacy of JTE-051 administered for 12 weeks in subjects with moderate 
to severe plaque psoriasis. 
• To evaluate the safety and tolerability of JTE-051 administered for 12 weeks in subjects 
with moderate to severe plaque psoriasis. 
• To evaluate the pharmacokinetics (PK) of JTE-051 administered for 12 weeks in subjects 
with moderate to severe plaque psoriasis. 
3 INVESTIGATIONAL PLAN 
3.1 Number of Sites and Subjects 
Multiple sites will be employed to ensure screening of sufficient number of subjects to 
randomize (in a 1:1:1:1:1 ratio) approximately 85 subjects (17 subjects per treatment group). 
3.2 Study Design 
This is a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group 
study in subjects with moderate to severe plaque psoriasis.  
Eligible subjects will be randomized at Visit 2 to receive JTE-051 50 mg, 100 mg, 150 mg, 
200 mg or placebo QD for 12 weeks. Approximately 85 subjects are planned to be 
randomized into 5 treatment groups. A follow-up visit will take place approximately 4 weeks 
after the last dose of study drug. Randomization will be stratified based on prior exposure of 
subjects to biologic therapy (i.e., biologic treatment-naïve vs. biologic treatment-experienced 
subjects). 
The study duration will be of approximately 20 weeks per subject: 
• Up to a 28-day Screening Period 
• A 12-week double-blind Treatment Period 
• A 4-week Follow-up Period 
3.3 Selection of Study Population 
Written informed consent must be obtained prior to performing any study-related procedures. 
A copy of the informed consent will be provided to the subject. 
3.3.1 Inclusion Criteria 
To qualify for the study, the subject must satisfy the following criteria: 
1. Male or female, ≥18 and ≤70 years of age at the time of Visit 1 (Screening Visit); 
2. Have had a diagnosis of moderate to severe plaque psoriasis for at least 6 months prior to 
Visit 1; 
3. Plaque-type psoriasis covering ≥10% of Body Surface Area (BSA) at Visit 1 and Visit 2 
(Baseline); 
4. Psoriasis Area and Severity Index (PASI) score ≥12 at Visit 1 and Visit 2; 
5. Static Physician’s Global Assessment (sPGA) score ≥3 at Visit 1 and Visit 2; 


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6. Body Mass Index (BMI) ≤40 kg/m2 at Visit 1; 
7. Females may participate if they meet one of the following criteria:  
• Surgically sterile (e.g., hysterectomy or bilateral oophorectomy), 
• At Visit 1, females with a documented history of lack of menses for ≥12 consecutive 
months with no other reversible medical etiology will be considered postmenopausal. 
• At Visit 1, if positive for lack of menses but onset ˂12 months, then an FSH >40 will 
be required to define post-menopausal status, otherwise subject is considered of 
childbearing potential, or 
• If of childbearing potential, with a negative pregnancy test at Visit 1 and if 
participates in heterosexual intercourse, agrees to be compliant with the consistent 
and correct use of acceptable methods of contraception as described below. 
Acceptable methods of birth control for this study are: 
a) one highly effective contraceptive method of birth control, which includes 
intrauterine devices, partner sterilization (with the appropriate post-vasectomy 
documentation of the absence of sperm in the ejaculate), tubal ligation, bilateral 
tubal occlusion, intrauterine hormone-releasing systems, in addition to 
b) one effective method of birth control, which includes male condom, female 
condom, cervical cap, diaphragm or contraceptive sponge all with spermicide 
(hormonal methods are not allowed). 
The above described contraception methods must be maintained for the duration of 
the study and for at least 30 days after the last dose of study drug. 
8. Male subjects must agree to use a barrier contraceptive method with spermicide for the 
duration of the study and for at least 12 weeks after the last dose of study drug or be 
sterilized (with appropriate post-vasectomy documentation of the absence of sperm in the 
ejaculate): 
Male subjects should be informed about the risks involved if pregnancy in female 
partners occurs while he is taking an investigative product and for at least 12 weeks 
after the last dose of study drug. Counseling on the appropriate contraception 
methods for their female partners should be given as follows: female partners of male 
subjects randomized in this study must be post-menopausal or in case of female 
partner of childbearing potential, unless surgically sterile, they must agree to use at 
least one form of an acceptable form of birth control (in addition to the method 
utilized by the male subject) for the duration of the study and for at least 12 weeks 
after the last dose of study drug. Please see inclusion criterion # 7 for a list of 
acceptable forms of birth control for the study (hormonal methods will be allowed for 
females partners of male subjects); 
Additionally, male subjects must not donate sperm for the duration of the study and 
within 12 weeks of the last dose of study drug. 
9. 
; 
10. Able and willing to complete an 
 questionnaire responses on a mobile device on 
a daily basis for the duration of the study; 
11. Able and willing to give written informed consent. 


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3.3.2 Exclusion Criteria 
The following criteria will exclude a subject from participating in the study: 
1. Medical history of treatment failure to any systemic agents (including biologic and 
non-biologic systemic agents) for plaque psoriasis; 
2. Presence 
of 
erythrodermic 
psoriasis, 
pustular 
psoriasis, 
guttate 
psoriasis, 
medication-induced psoriasis or other skin conditions at (e.g., clinically-significant 
eczema or severe acne) that could interfere with study evaluations at Visit 1; 
Note: Subjects with psoriatic arthritis will not be excluded from the study provided that 
criteria for cutaneous severity of psoriasis, as well as all other study restrictions required 
by the protocol are met. 
3. Presence or history of any itch due to underlying conditions other than plaque psoriasis 
which cause or influence pruritus of the skin (e.g., drug induced pruritus, significant other 
systemic diseases with itch) within 12 months prior to Visit 1; 
4. Does not meet all study restrictions, including previous/concomitant medication 
restriction criteria, as described in Section 3.5.4.1; 
5. Leucocyte count of <3.0 X 109/L (<3000/mm3), absolute neutrophil count of 
<1.5 X 109/L (<1500/mm3) or absolute lymphocyte count <0.8 X 109/L (<800/mm3) at 
Visit 1; Hemoglobin <11 g/dL or platelet count <100,000/mm3 at Visit 1; 
6. ALT >2.0 X the upper limit of normal (ULN) or AST >2.0 X the ULN at Visit 1; 
7. Evidence of renal impairment; serum creatinine >1.5 X the ULN at Visit 1; 
8. Hemoglobin A1c (HbA1c) >8.5% at Visit 1; 
9. Serum triglycerides >400 mg/dL at Visit 1; 
10. Positive viral serology at Visit 1 for: 
• Human immunodeficiency virus (HIV): positive HIV antibodies (Ab) or 
• Hepatitis B virus (HBV): positive total hepatitis B core (HBc) Ab or positive 
hepatitis B surface antigen (HBsAg) or 
• Hepatitis C virus (HCV): positive HCV Ab; 
11. Positive drug of abuse test results at Visit 1; 
Note: Non-abusive use of prescription drugs, according to the Investigator’s judgment is 
permitted, provided that the concomitant medications restrictions required by the protocol 
are met. 
12. Positive Purified Protein Derivative (PPD) test or QuantiFERON®-TB Gold-In-Tube test , 
positive chest radiographic findings for tubercle bacillus (TB) or any other evidence of 
active or latent TB; 
• For subjects with a history of Bacille Calmette-Guérin (BCG) vaccination or in case 
PPD test fails, the QuantiFERON®-TB Gold-In-Tube test should be performed;  
• 
A PPD test is considered positive if, at 48 to 72 hours of administration, the 
induration (not erythema) obtained is ≥5 mm. The reaction must be read between 
48 and 72 hours after administration (a subject that does not return after 72 hours 
must be rescheduled for a repeat PPD test);  


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• 
If QuantiFERON®-TB Gold-In-Tube test is indeterminate, a retest is allowed if 
results can be obtained within the timeframe allowed between Visit 1 and Visit 2. If 
the retest is also indeterminate, the subject will be excluded from the study; 
• 
The QuantiFERON®-TB Gold-In-Tube test should not be performed within ≤4 weeks 
from the date of a live vaccination;  
• Subjects who have had household contact with a person with active TB are excluded, 
unless appropriate and documented prophylaxis for TB was administered. 
13. History of live vaccination within 4 weeks prior to Visit 2 or have a live vaccination 
planned during the course of the study or within 6 weeks after the last dose of study drug; 
14. Have donated or received blood or blood products within 4 weeks prior to Visit 1; 
15. History of a clinically-significant infection (e.g., infection that required oral antimicrobial 
or antiviral therapy) within 8 weeks prior to Visit 2, except for treated urinary tract 
infections, which will be permitted if resolved >1 week prior to Visit 2; 
16. History of opportunistic infections or infection requiring hospitalization or parenteral 
antibiotic, antiviral, antifungal or antiparasitic therapy within 6 months prior to Visit 2 or 
history of recurrent infections or conditions predisposing subject to chronic infections 
(e.g., bronchiectasis, chronic osteomyelitis); 
17. History of shingles within 12 months prior to Visit 1 or known history of 
disseminated/complicated herpes zoster; 
18. History or presence of any lymphoproliferative disorder (e.g., Epstein Barr Virus-related 
lymphoproliferative disorder, lymphoma, leukemia, multiple myeloma) or signs and 
symptoms suggestive of current lymphatic disease, such as Hodgkin's or Non-Hodgkin's 
lymphoma; 
19. History of or current malignancies with the exception of adequately treated or excised 
non-metastatic basal cell or squamous cell carcinoma of the skin or cervical carcinoma 
in situ >6 months prior to Visit 1; 
20. History of organ transplantation; 
21. A history of substance abuse, drug addiction or alcoholism within 12 months prior to 
Visit 1. Alcoholism is defined as the consumption of more than 28 units of alcohol a 
week (an alcohol unit is defined as 300 mL of beer, 100 mL of wine, or 25 mL of hard 
liquor);  
22. History of decompensated heart failure, fluid overload, myocardial infarction, 
uncontrolled arterial hypertension or evidence of ischemic heart disease or other serious 
cardiac disease within 12 months prior to Visit 1; 
 
2
 


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29. Pregnant or nursing at Visit 1 or Visit 2 or plan to become pregnant or initiate 
breastfeeding during the study and within 12 weeks after the last dose of study drug; 
30. Significant history of drug or other hypersensitivities per the investigator (e.g., multiple 
drug allergies or severe allergic reactions, including angioedema); 
31. History or presence of any other clinically relevant medical condition or disease or 
laboratory abnormality including hepatic, renal, gastroenterologic, respiratory, 
cardiovascular, 
endocrinologic, 
, 
psychiatric 
(e.g., schizophrenia, manic-depressive disorder, treatment-resistant major depression), 
immunologic (e.g., immunocompromised subjects or subjects with autoimmune 
conditions other than psoriasis, such as type I diabetes), m
 bone 
(
) or hematologic (e.g., sickle cell) disease that, in the opinion of the 
Investiga or, may place the subject at unacceptable risk for study participation and may 
prevent the subject from completing the study (e.g., low life expectancy, high risk of 
non-compliance) or would interfere with the study conduct or data interpretation, 
according to the Investigator’s judgment; 
32. Cannot communicate reliably with the Investigator (including inability to complete the 
self-assessment questionnaires) or are unlikely to cooperate with the requirements of the 
study. 
 
 


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3.4 Removal of Subjects from the Study 
A subject will not participate further in the study under the following conditions: 
1. 
Withdrawal by Subject: subjects have the right to withdraw from the study at any time. 
However, if a subject withdraws consent because of experiencing an adverse event, the 
reason for subject termination should be documented as the adverse event. 
2. 
Adverse Event: a clinical or biological adverse event or intercurrent condition(s), 
requiring study drug discontinuation, whether or not related to the study drug 
If grade 3 findings (defined as severe or medically significant but not immediately 
life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care activities of daily living [ADL] such as bathing, dressing, undressing, 
feeding self, using the toilet, taking medication, but not bedridden), according to the 
CTCAE29, are noted in a subject, he/she must be promptly evaluated by the Investigator 
(including repeat tests, evaluation of the baseline parameters, concomitant medications, 
etc.) for potential withdrawal from the study. Every effort should be made to discuss 
with the study’s Medical Monitor prior to final decision, unless not feasible, based on 
safety considerations.  
Notes:  
• The investigator may decide to evaluate or withdraw the subject from the study based 
on findings of lesser than grade 3 severity, according to his/her judgment. 
 
 
l 
 
3. 
Consistent Non-compliance with Study Drug (i.e., <80% or >120% compliance at two 
consecutive study visits; exceptions on a case-by-case basis may be permitted if 
approved by Sponsor or designee). 
Note: Compliance will be evaluated at every study visit during the Treatment Period. If 
compliance of <80% or >120% is identified at a study visit, the Investigator or designee 
is to counsel the subject and ensure steps are taken to improve compliance. 
4. 
Inclusion/Exclusion Criteria Not Met: If a subject who did not meet any of the study 
inclusion or exclusion criteria is identified after the randomization, the Investigator, 
Medical Monitor and Sponsor will review that subject profile, including the medical 
history, prior and current concomitant medications, physical examination, vital signs, 
12-lead ECGs and clinical laboratory test results. Since such deviations are usually noted 
after randomization, the decision to be made is to allow the subject to continue the study 
or not. For such cases, an exception may be permitted on a case-by-case basis if the 
subject was randomized into the study due to a minor error determined to be of no 
clinical and/or safety risk to the subject. Some of the examples where case-by-case basis 
exceptions may be allowed are as follows: 


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• A subject who had a minor deviation from the inclusion/exclusion criteria defined 
for the efficacy evaluation purpose (e.g., inclusion criteria 1 through 6, exclusion 
criteria 1 through 4). 
• 
A subject who had a minor deviation in clinical laboratory test results from the 
cut-off values defined in exclusion criteria 6 through 11. 
5. 
Protocol Violation: the subject is non-compliant with regard to this protocol (other than 
the withdrawal criteria 3 and 4 listed above), as determined by Sponsor or the 
Investigator on a case-by-case basis. 
6. 
Lost to Follow-up 
7. 
Death 
8. 
Study Terminated by Sponsor: the sponsor may suspend or terminate the study or part of 
the study at any time for any reason. 
9. 
Pregnancy 
10. Investigator Decision: the Investigator decides a subject should be discontinued for any 
reasons other than those already mentioned (actual reason must be documented by site). 
11. Other: actual reason must be documented by site. 
Subjects who are removed from the study or withdraw consent to participate in the study 
after receiving at least one dose of study drug will be requested to complete an 
Early Termination Visit at which time the subject will undergo all the procedures described 
for Visit 6. Every effort should be made to perform the Visit 6 assessments as soon as 
possible after the last dose of study drug and the decision of discontinuation is made and 
prior to any changes made in the subject’s anti-psoriasis therapy. Additionally, at 
approximately 4 weeks after study drug discontinuation, subject should return for a 
Follow­up Visit, where all procedures as described at Visit 7 should be performed. 
 


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3.5  Study Procedures 
 
Figure 1. Planned Study Schema 
 
JTE-051 50 mg QD (N=17) 
JTE-051 100 mg QD (N=17) 
Placebo QD (N=17) 
Treatment 
12 weeks 
Up to 4 weeks 
V2 
Rand. 
V4 
 
V = Study Visit 
Rand. = Randomization 
FU = Follow-up   
V1 
2 weeks 2 weeks 
4 weeks 
4 weeks 
Screening 
4 weeks 
 
Follow-up 
Approx. 4 weeks 
V6 
4 weeks 
V7 
FU 
= Double-blind Treatment Period 
V5 
JTE-051 150 mg QD (N=17) 
JTE-051 200 mg QD (N=17) 
V3 


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Table 1. 
Planned Schedule of Study Procedures 
 
Note: All study procedures should be performed at each study visit prior to study drug administration; 
except for appropriate PK samples collection procedures as discussed below (see Figure 2). When 
scheduled at the same time points, ECG and vital sign parameters collection activities should be 
performed prior to procedures involving venipuncture 
. 
Screening
Period
Follow-up
Period
Duration/ Study Week (Day)a
 Up to 4 
weeks
Week 0
(Day 1)
Week 2
(Day 14±2)
Week 4
(Day 28±2)
Week 8
(Day 56±2)
Week 12
(Day 84±2)
Week 16
(Day 112±2)
Visit
1
2
3
4
5
6
7
Sign Informed Consent
X
Inclusion/ Exclusion Criteria
X
X
Medical History
X
Demographic Information
X
Review Prior/ Concomitant Medications
X
X
X
X
X
X
X
Physical Exam
X
X
X
X
X
X
N
Vital Signs
X
X
X
X
X
X
X
Body Weight
X
X
X
Height and Calculate BMI 
X
12-Lead ECG
X
X
X
X
Chest Radiographyc
X
TB test (quantiFERON gold OR PPD Test)
X
Drugs of Abuse Screen & alcohol
X
Viral Serology (HBs Ag, HCV Ab, HIV Ab)
X
FSHd
X
HbA1c
X
Pregnancy Test (all females)d
X
X
X
X
X
X
X
Serum Biochemistry
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
Coagulation
X
X
X
X
X
Lipid Profile
X
X
X
X
X
Serum IgG, IgM and IgA 
X
X
25-hydroxyvitamin D
X
Psoriasis Body Surface Area
X
X
X
X
X
X
X
Bone-specific ALP
X
X
X
PASI
X
X
X
X
X
X
X
sPGA
X
X
X
X
X
X
X
Skindex 16
X
X
X
X
X
X
Itch NRS 
I
Digital Photographyg
X
X
Randomization using IWRS
X
Access IWRS and Dispense Study Drugh
X
X
X
X
Collect Study Drug and Check Compliancej
X
X
X
X
Study Drug Administrationk
X
X
X
X
JTE-051 PK Blood Samplesl
X
X
X
X
X
Document Adverse Eventsm
X
X
X
X
X
X
X
Treatment  Period


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a. 
The target day for each visit after randomization will be calculated relative to the date of Randomization 
Visit (Visit 2) and not relative to the date of the previous visit. All visits should be performed within the 
windows specified in the table. Every attempt should be made to have the subject attend each visit as 
scheduled. The investigational site is encouraged to a make a reminder phone call to the subject 
approximately a day or two before the scheduled visit. However, if a subject is unable to attend a visit 
within the specified windows, the visit should be scheduled as closely as possible to these windows. A 
subject should not skip a protocol-specified visit due to scheduling difficulties. 
b. 
c. 
Chest radiography may not be performed if it has been performed within 12 weeks of Visit 1 and 
documentation is available for review by the Investigator and inclusion in the subject’s file. 
d. At Visit 1, serum pregnancy test will be performed for all female subjects. At Visits 2 through 7, urine 
pregnancy tests will be performed only for female subjects of child bearing potential. At Visit 1, females 
with a documented history of lack of menses for ≥12 consecutive months with no other reversible medical 
etiology will be considered postmenopausal. If the female is positive for lack of menses but onset has been 
˂12 months, then an FSH >40 will be required to define post-menopausal status, otherwise subject is 
considered of childbearing potential. 
e. 
Both WI-NRS and AI-NRS during a 24-hour recall period will be recorded by the subject once daily from 
screening through the last visit. 
f. 
 
 
 
g. All subjects will be required to take photographs of the 
 
 four half-body views (i.e., upper anterior, lower anterior, upper posterior, and 
lower posterior). However, if collecting photographs is raised as the reason for not participating in the 
study, the subject still can be part of the study without collecting photographs. In all the photographs, 
subject identification will be blinded. 
h. At Visit 2 through Visit 5, randomized subjects will receive sufficient study drug blister cards for the 
period between visits. At Visit 6, study drug will not be dispensed. If a study subject discontinues study 
drug prematurely, the termination should be recorded as soon as possible after the decision has been made. 
i. 
. 
j. 
Subjects will be instructed to bring all used and unused blister cards to each study visit for accountability 
purposes. Study drug compliance will be calculated by the site at each visit during the Treatment Period 
starting at Visit 3, based on the number of tablets dispensed to and returned by the subject. 
k. Oral administration for 12 weeks starting on the day of randomization at Visit 2, QD in the morning, 
regardless of meals. On study visit days, subjects should take their scheduled study treatment from their 
existing study drug supply (if available) at the site, under the supervision of the investigator or designee 
after all study-related procedures have been performed (except for Visit 6, when no study drug will be 
administered, as the last dose will be taken the day prior to the visit).  
l. 
See Figure 2 for a detailed description of dosing and PK sampling time points. 
m. Adverse event information will be collected at the specified time points as well as at any time when a site 
staff member becomes aware of an AE after the subject signs the informed consent for the study. However, 
stable or improving pre-existing conditions detected through the screening procedures during the Screening 
Period (e.g., abnormalities in ECG, physical examination, ne
, vital signs and 
laboratory tests) are considered to be medical history and should be documen ed accordingly. 


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Figure 2. 
Dosing and Pharmacokinetic Sample Collection Time  
a. 
The exact date and time of dose at each visit at the site will be collected. 
b. The exact date and time of the last three doses prior to the PK sample collection will be collected. 
c. 
The PK samples at pre-dose point (i.e., samples obtained prior to the morning dosing of the study drug at 
the site) are mandatory in all subjects at all sites. Sample collection date and time will be collected. 
d. The PK samples at trough point (relative to dosing of the study drug at the day prior to the visit) are 
mandatory in all subjects at all sites. Sample collection date and time will be collected. 
e. 
Every effort should be made to collect post-dose PK samples (relative to the morning dosing of the study 
drug at the site) from as many subjects/treatment as possible. Sample collection date and time will be 
collected.  
f. 
The sampling time between post dose blocks (boxes in Figure 2) should be separated by at least 1 hour.  


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3.5.1 Screening Period 
Day -28 (Visit 1) to Day 1 (Visit 2) 
Following signature of the informed consent for the study, screening procedures to confirm 
eligibility may be performed across multiple days, as needed, during the Screening Period. 
Washout of previous medications can begin once the subject signs the informed consent 
regardless of the 28 day screening period. If a subject arrives for a visit not having fasted 
(overnight fast, at least 10 hours prior to blood and urine sample collection), all study 
procedures except the blood/urine collection activities may be performed; the blood/urine 
collection will be rescheduled on a subsequent day within the visit window and the subject 
will be reminded to fast overnight.  
Please refer to Table 1for the list of screening procedures to be performed in the study. A 
one-time repeat of the screening laboratory (except for drugs of abuse and alcohol, viral 
serology and pregnancy tests), vital sign and ECG assessments is permitted, if considered 
appropriate by the Investigator, except stated otherwise (e.g., up to three-time repeat of blood 
pressure measurements at the Screening Visit is permitted). The repeat test(s) result(s) are to 
be utilized for subject qualification purposes. If the repeat test results are outside the 
protocol-required range, the subject should be excluded from the study.  
Re-screening of subjects may be permitted on a case-by-case basis, pending discussion and 
approval by the Medical Monitor. 
3.5.2 Double-blind Treatment Period 
Day 1 (Visit 2) to Day 84 ±2 (Visit 6/Week 12) 
Please refer to Table 1 for the by-visit list of procedures to be performed in the study during 
this period.  
All visits during the Double-blind Treatment Period (i.e., including Visit 2 [Randomization 
Visit]), should be performed under fasted conditions (overnight fast, at least 10 hours prior to 
blood and urine sample collection). If a subject arrives for a visit not fasted, then all study 
procedures except the blood/urine collection activities may be performed; the blood/urine 
collection will be rescheduled on a subsequent day within the visit window and the subject 
will be reminded to fast overnight. Exception to this would be Visit 2, at which all study 
procedures have to be completed within the same session, therefore, if the subject is not 
fasted, the full visit should be rescheduled. 
All visits should be performed within the windows specified in Table 1. Every attempt 
should be made to have the subject attend each visit as scheduled. The site is encouraged to a 
make a reminder phone call to the subject approximately a day or two before the scheduled 
visit. However, if a subject is unable to attend a visit within the specified windows, the visit 
should be scheduled as closely as possible to these windows. A subject should not skip a 
protocol-specified visit due to scheduling difficulties. 
Subjects will be administered the first dose of study drug at the site, upon completion of all 
pre-dosing procedures and randomization at Visit 2; subsequently, they will be instructed to 
self-administer study drug QD, in the morning, regardless of food. However, subjects should 
not take study drug in the morning of the day of a study visit until after all study procedures 


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have been completed (except for appropriate PK samples collection procedures as discussed 
in Figure 2). On those days, study drug will be administered at the site by the study personnel 
from the subject’s previously supplied study drug blister cards, if available, except for Visit 6, 
when no study drug will be administered, as the last dose will be taken the day prior to the 
visit. If the subject inadvertently took study drug on the day of the study visit, prior to the 
visit, he/she may complete the visit and the actual date and time of the last dose prior to the 
PK blood samples collection will be accurately recorded. 
The exact date and time of the last three doses prior to the PK sample collection and the 
dosing time after the initial (trough) PK sample collection at each visit during the Treatment 
Period (i.e., Visits 2 through 6) should be documented.  
Study drug will not be administered and all remaining study drug will be collected from the 
subjects at Visit 6.  
If a subject discontinues the study prematurely after receiving at least one dose of study drug, 
an Early Termination Visit should be completed at which all procedures listed for the Visit 6 
should be performed, if possible, prior to any changes made in the subject’s anti-psoriasis 
therapy. 
3.5.3 Follow-up Period 
Day 84 ±2 (Visit 6/Week 12) to Day 112 ±2 (Visit 7/Week 16)  
The Follow-up Visit will occur approximately 4 weeks after the last dose of study drug. 
Similar to all other study visits, subjects should arrive under fasted conditions (i.e., overnight 
fast, at least 10 hours prior to blood and urine sample collection). Please refer to Table 1 for 
the list of follow-up procedures to be performed.  
For subjects who discontinue the study prematurely after receiving at least one dose of study 
drug, follow-up procedures, as described for Visit 7 should be performed approximately 
4 weeks after the last dose of study drug. 
 
 
 


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3.5.4 Study Restrictions  
3.5.4.1 Previous and Concomitant Medication Restrictions 
Please refer to the tables below for the list. 
Table 2. 
Psoriasis Therapy Restrictions  
Prohibited Period 
Medication(s) 
Within 12 weeks (or 5 times the PK 
half­life, whichever is longer) prior to 
Visit 2 and through Visit 7  
• Biologic agents (marketed or investigational) 
• Investigational systemic therapies 
Within 28 days prior to Visit 2 and 
through Visit 7  
• Investigational topical therapies  
• Acitretin 
• Methotrexate 
• Cyclosporine 
• Apremilast 
• Fumaric acid ester 
• Oral/parental corticosteroids (including 
intramuscular, intradermal or intraarticular 
administration) 
• Psoralen plus ultraviolet A (PUVA) therapy 
• Ultraviolet A (UVA) therapy 
• Ultraviolet B (UVB) therapy 
Within 14 days prior to Visit 2 and 
through Visit 7  
• Topical steroids 
• Topical vitamin A or D analog preparations 
• Anthralin 
• Topical calcineurin inhibitors (e.g., cyclosporine)  
• Topical salicylic acid 
Use of one (1) topical moisturizer (e.g., Cetaphil®) will be allowed during the study. This 
may not be used within 12 hours prior to the study visit.  
Note: If a subject develops significant clinical exacerbation of their psoriasis at any time 
during the entire duration of the study, study drug can be withdrawn and the subject will be 
treated clinically per existing standard of care. 
 


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Table 3. 
Other Medications Restrictions 
Prohibited Period 
Medication(s) 
Any time prior to or during the study 
(through Visit 7) 
• Antipsychotic therapy 
• Anti-retroviral therapy and alpha-interferon 
• Anti-cancer chemotherapy 
Within 12 weeks prior to Visit 2 and 
through Visit 7 
• Monoamine oxidase inhibitors 
• Isoniazid 
Within 28 days prior to Visit 2 and through 
Visit 7 
• Doxycycline and minocycline 
• Pentoxifylline 
• Sulfones (e.g., Dapsone) 
• Colchicine and systemic metronidazole 
• Vitamin B6 at doses >100 mg/day 
• Cannabinoids, including marijuana. 
 
 
 
 
Chronic use* 
• NSAIDs 
*NSAID cannot be used for more than 3 days in a week; low dose prophylactic use of aspirin 
is allowed. 


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General Medication-related Protocol Instructions: 
 
 
 
 
• Generally, medication dose/route of administration changes or initiation of new 
medications during the conduct of the study is not recommended unless such actions are 
considered medically necessary; 
• All medications taken by the subject, including over-the-counter, herbal, traditional, 
ayurvedic compounds (whether permitted or excluded by the protocol) must be 
documented in the case report form (CRF); 
• Contact the Medical Monitor with questions regarding prior/concomitant therapy.  
3.5.4.2 Dietary Restrictions 
Grapefruit juice, grapefruit and sour oranges are not permitted for at least 3 days before 
beginning the Treatment Period and during the Treatment Period. 
3.5.4.3 UV Related Restrictions 
Every effort should be made to minimize/eliminate unnecessary sun exposure during the 
study. If sun exposure is unavoidable, sun screen with a sun protection factor (SPF) of 
minimum 30 should be utilized. Intentional tanning is prohibited throughout the study. 
3.5.4.4 General Restrictions 
• Following enrollment in the study, subjects should continue all non-pharmacological 
therapies, such as physical therapy, as indicated and deemed appropriate for his/her 
physical condition. 
• Subjects should not donate blood or receive any blood or blood products throughout the 
study duration (i.e., from Visit 2 through the Follow-up Visit). 
• Routine household contact with children or others vaccinated with live vaccine 
components (e.g., varicella, or attenuated typhoid fever, oral polio, attenuated rotavirus or 
inhaled flu vaccines) should be avoided during the study and for 6 weeks after the last 
dose of study drug. 
• Travel to countries with known high prevalence of tuberculosis should be avoided from 
the time of signing the informed consent through the Follow-up Visit. 
• Local standard recommendations (e.g., insect repellents) should be followed to minimize 
the risk of infection with the Zika virus in subjects enrolled in the study. 


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3.5.6 Procedure Definitions 
3.5.6.1 Static Physician’s Global Assessment 
The sPGA will be performed on psoriatic lesions overall by the Investigator according to the 
schedule summarized in Table 1. 
The sPGA assessments should be performed on all psoriatic lesions by the same evaluator 
throughout the study. The sPGA is used to determine the severity of subject’s psoriatic lesion 
at a given time point. The psoriatic lesion will be graded for induration, erythema and scaling 
based on the scales below. The sum of the 3 scales will be divided by 3 to obtain the final 
sPGA score. 
Induration (I)  
0 = no evidence of plaque elevation 
1 = minimal plaque elevation, ~0.25 mm 
2 = mild plaque elevation, ~0.5 mm 
3 = moderate plaque elevation, ~0.75 mm 
4 = marked plaque elevation, ~1 mm 
5 = severe plaque elevation, ~1.25 mm or more 
Erythema (E)  
0 = no evidence of erythema, hyperpigmentation may be present 
1 = faint erythema 
2 = light red coloration 
3 = moderate red coloration 
4 = bright red coloration 
5 = dusky to deep red coloration 
Scaling (S)  
0 = no evidence of scaling 
1 = minimal; occasional fine scale over less than 5% of the lesion 
2 = mild; fine scale dominates 
3 = moderate; coarse scale dominates 
4 = marked; thick, nontenacious scale dominates 
5 = severe; very thick tenacious scale predominates  
Add I+E+S = _______________/3 = ________ (Total Average) 
Physician’s Static Global Assessment based upon above Total Average 
0 = Cleared, except for residual discoloration 
1 = Minimal – majority of lesions have individual scores for I+E+S/3 that averages 1 
2 = Mild – majority of lesions have individual scores for I+E+S/3 that averages 2 
3 = Moderate – majority of lesions have individual scores for I+E+S/3 that averages 3 
4 = Marked – majority of lesions have individual scores for I+E+S/3 that averages 4 
5 = Severe – majority of lesions have individual scores for I+E+S/3 that averages 5 
Note: Scores should be rounded to the nearest whole number (e.g., if the total is ≤1.49, the 
score should be 1; if the total is ≥1.50, the score should be 2) except if the score is ˃0 and ˂1, 
score should be treated as 1. 


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3.5.6.2 Psoriasis Area and Severity Index 
Psoriasis area and severity index (PASI), a quantitative rating score to assess the severity of 
psoriatic lesions based on the area coverage and plaque appearance will be performed 
according to the schedule summarized in Table 1. 
For a given subject, the PASI assessments should be performed by the same evaluator 
throughout the study. 
The PASI score 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 to 4. The area 
covered by lesions on each body region is estimated as a percentage of the total area of that 
particular body region. Further practical details help the assessment: 
1. The neck is assessed as part of the head. 
2. The axillae and groin are assessed as part of the trunk. 
3. The buttocks are assessed as part of the lower limbs. 
4. When scoring the severity of erythema, scales should not be removed. 
Because the head and neck, upper limbs, trunk and lower limbs correspond to approximately 
10%, 20%, 30% and 40% of the body surface area, respectively, the PASI score is calculated 
using the following formula: 
PASI = 0.1(EH+IH+DH)AH + 0.2(EU+IU+DU)AU + 0.3(ET+IT+DT)AT + 0.4(EL+IL+DL)AL 
Where,  
The PASI scores can range from 0, corresponding to no signs of psoriasis, up to a theoretic 
maximum of 72.0, corresponding to maximal signs of psoriasis. 
 
 


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Table 7. 
The PASI Scoring 
Body 
region 
Erythema (E) Thickening 
(plaque elevation, 
induration, I) 
Scaling 
(desquamation, D) 
Area score (based on true 
area %, A)* 
Head (H)† 
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)‡ 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)§ 
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 entered in the CRF. 
† 
Neck is assessed as part of the Head (H) body region. 
‡ 
Axillae and groin are assessed as part of the Trunk (T) body region. 
§ 
Buttocks are assessed as part of the Lower limbs (L) body region. 
 
 


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3.5.6.3 Psoriasis Body Surface Area Assessment 
The BSA assessment will be performed by the same Investigator throughout the study 
according to the schedule summarized in Table 1. 
The total BSA affected by plaque-type psoriasis will be estimated from the percentages of 
areas affected, including head, trunk, upper limbs and lower limbs. The following 
calculations will be done: each reported percentage will be multiplied by its respective body 
region corresponding factor (head = 0.1, trunk = 0.3, upper limbs = 0.2, lower limbs = 0.4). 
The resulting 4 values will be added up to estimate the total BSA affected by plaque-type 
psoriasis. For a given subject, the BSA assessments should be performed by the same 
evaluator throughout the study. 
3.5.6.4 Skindex-16  
Subjects will complete Skindex-16 questionnaire according to the schedule summarized in 
Table 1. 
Skindex-16 is a 16-item, skin-related quality of life questionnaire (QOL) and has 3 domain 
scores: symptoms, emotions and functioning. Each 16-item QOL questionnaire will be 
reported as a scale 0 to 6. Each raw score will be multiplied by 16.667, thus all responses will 
be transformed to a linear scale of 100 (i.e., from 0 [no effect] to 100 [effect experienced all 
the time]). If more than 25% of the responses missing, the scale is considered missing. An 
item with multiple answers is considered missing.  
3.5.6.5 Itch Numeric Rating Scale 
The Itch NRS is a validated, self-reported instrument for measurement of itch intensity. It 
uses a 24-hour recall period and asks subjects to rate the intensity of their itch on an 11-point 
scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater 
itch intensity. In this study, both worst itch intensity (WI-NRS) and average itch intensity 
(AI-NRS) during a 24-hour recall period will be captured using the 
.  
The Itch NRS score will be recorded by the subject using the 
 once daily 
(before study drug administration once the subject is randomized) preferably at the same time 
of the day each day from Screening through the last visit.  
3.5.6.6 Physical Examination 
The physical examinations will be performed by a physician or qualified designee according 
to the schedule summarized in Table 1 and will include examination of the following body 
systems: general appearance, skin (including hair and nails), HEENT (head, ears, eyes, nose, 
throat), 
neck/thyroid, 
chest/lungs, 
cardiovascular, 
gastrointestinal, 
l, 
psychiatric/emotional, lymphatic and musculoskeletal systems.  
3.5.6.7 Height and Weight Measurements and Body Mass Index Calculation 
The height and weight measurements will be performed according to the schedule 
summarized in Table 1. Subjects will remove their shoes and wear light clothing in order to 
be consistent between measurements of height and/or weight. The BMI will be calculated at 
Visit 1 using the following equation: (weight (kg)/[height (m)2]), where the weight in 


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kilograms will be documented to one decimal place and the height in centimeters will be 
rounded to the nearest whole number. 
3.5.6.8 Medical History 
A complete medical history will be performed at Visit 1 and will include evaluations for past 
or present conditions. Specifically, any known history of psoriatic arthritis will be 
documented. 
Any pre-existing conditions that are detected at Visit 1 (e.g., abnormalities in ECG, physical 
examination, vital signs and laboratory tests) are considered to be medical history. 
3.5.6.9 Vital Signs 
Vital sign assessments including blood pressure, heart rate, respiratory rate and body 
temperature (°C) will be performed in sitting position according to the schedule summarized 
in Table 1. Subjects must rest in a sitting position for at least 5 minutes in preparation for 
blood pressure and heart rate assessments. 
3.5.6.10 12-Lead ECG  
12-lead ECG recordings and conduction intervals including RR, PR, QRS, QT and 
Fridericia-corrected QT interval (QTcF) will be obtained according to the schedule 
summarized in Table 1. The Investigator or designee will review and assess each individual 
ECG report and the interpretation of the actual findings, rather than the automatic printout, 
results on the ECG tracing will be documented. Subjects will lay supine without pillows for 
at least 3 minutes prior to the 12-lead ECG assessment. 
3.5.6.11 Hematology  
Blood samples to assess complete blood count including erythrocytes, hematocrit (Hct), 
hemoglobin (Hgb), platelets, leucocytes and differential (percent and absolute [neutrophil, 
eosinophil, basophil, lymphocyte, monocyte]) will be obtained under fasted conditions 
according to the schedule summarized in Table 1. 
3.5.6.12 Serum Biochemistry  
Blood samples to assess ALT, ALB, ALP, AST, bilirubin, blood urea nitrogen (BUN), 
calcium, carbon dioxide, chloride, creatinine phosphokinase (CPK), creatinine (CRN), 
gamma-glutamyl transferase (GGT), globulin, glucose, CRP, lactate dehydrogenase (LDH), 
phosphate, potassium, protein, sodium, urate, will be obtained under fasted conditions 
according to the schedule summarized in Table 1. 
3.5.6.13 Bone Specific ALP 
Blood samples to measure bone specific ALP will be obtained according to the schedule 
summarized in Table 1. 


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3.5.6.14 Lipid Panel 
Blood samples to measure cholesterol, low-density lipoprotein cholesterol (LDL-C), 
high­density lipoprotein cholesterol (HDL-C) and triglycerides will be obtained according to 
the schedule summarized in Table 1. 
3.5.6.15 Serum Immunoglobulins 
Blood samples to measure Serum IgG, IgM and IgA will be obtained according to the 
schedule summarized in Table 1. 
3.5.6.16 25-hydroxyvitamin D 
Blood samples to measure 25-hydroxyvitamin D will be obtained according to the schedule 
summarized in Table 1. 
3.5.6.17 Coagulation 
Blood samples to assess thromboplastin time (PT) and activated partial thromboplastin time 
(aPTT) will be obtained as measures of blood coagulation according to the schedule 
summarized in Table 1. International normalized ratio will also be calculated. 
3.5.6.18 Viral Serology  
Blood samples to assess HbcAb (HBsAg), HCV Ab and HIV Ab will be obtained at the 
Visit 1. 
3.5.6.19 Drugs of Abuse and Alcohol Screen 
Urine samples to assess amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine 
metabolites, opiates, ethanol, methadone, methylenedioxymethamphetamine and oxycodone 
will be obtained at Visit 1.  
3.5.6.20 Urinalysis  
Urine samples to assess bilirubin, occult blood, color, glucose, ketone, leukocyte esterase, 
nitrite, pH, protein, specific gravity, turbidity and urobilinogen, as well as for a microscopic 
exam (to be performed only if the macroscopic exam is abnormal), including bacteria, cast, 
crystals, epithelial cells, mucus threads, erythrocytes, leukocytes and budding yeast will be 
obtained under fasted conditions according to the schedule summarized in Table 1. 
3.5.6.21 Glycosylated Hemoglobin 
Blood samples to measure glycosylated hemoglobin will be obtained at Visit 1. 
3.5.6.22 Pregnancy Test  
Blood samples will be collected at Visit 1 for a serum pregnancy test to assess human 
chorionic gonadotropin (βHCG) levels for all female subjects. At Visits 2 through 7, urine 
pregnancy tests will be performed only for female subjects of childbearing potential.  


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3.5.6.23 Follicle-stimulating Hormone 
Blood samples to assess the menopausal status will be collected at Visit 1 from female 
subjects who report a history compatible with menopause i.e. positive for lack of menses but 
onset ˂12 months with no other identified biological/surgical cause.  
3.5.6.24 PPD Test and QuantiFERON®-TB Gold Test 
The PPD skin test (also known as Mantoux test) or the QuantiFERON®-TB Gold 
(Gold-In-Tube test according to the local standard of care) may be used as tuberculosis 
screening tools for the study during the Screening Period. For subjects with a history of 
Bacille Calmette-Guérin (BCG) vaccination or in case PPD test fails, the QuantiFERON®-TB 
Gold-In-Tube test should be performed. 
If the PPD test is conducted, the reaction must be read between 48 and 72 hours after 
administration (a subject that does not return after 72 hours must be rescheduled for a repeat 
PPD test). The reaction will be measured in millimeters of the induration (palpable, raised, 
hardened area or swelling). The reader will not measure erythema (redness). The diameter of 
the indurated area will be measured across the forearm (perpendicular to the long axis). An 
induration of 5 or more millimeters is considered positive. 
If the QuantiFERON®-TB Gold-In-Tube test is performed, blood samples will be collected, 
processed and shipped during the Screening Period, according to the laboratory instructions. 
In the case of an indeterminate QuantiFERON®-TB Gold-In-Tube test, the test may be 
repeated one time if results can be obtained in time prior to Visit 2. If the retest is also 
indeterminate, subject will not be eligible for the study (screening failure) and re-training of 
the applicable parties at the site and/or central laboratory level should be considered. 
Subjects who have had household contact with a person with active tuberculosis are 
excluded, unless appropriate/documented prophylaxis for tuberculosis was successfully 
administered. 
3.5.6.25 Chest Radiography 
Chest radiography to include two views (anterior-posterior and lateral) will be obtained 
during the Screening Period in all subjects. If an adequate chest radiography has been 
performed within 3 months (12 weeks) prior to Visit 1 and documentation (including 
interpretation of TB status) is available, it will be provided to the Investigator for review and 
documented in the subject’s record. This radiography may be utilized to determine eligibility 
of the subject. To be considered eligible for the study, the radiography must be negative for 
active tuberculosis infection; however the Investigator may decide to exclude the subjects 
based on clinically-significant chest radiography findings other than tuberculosis (e.g., due to 
an acute or chronic inflammatory process), according to his/her judgment.  
 
 


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3.5.6.28 Photography 
All subjects will be required to take photographs of 
d 
a
 four half-body views (i.e., upper anterior, lower 
anterior, upper posterior, and lower posterior) according to the schedule presented in Table 1. 
However, if collecting photographs is raised as the reason for not participating in the study, 
the subject still can be part of the study without collecting photographs. In all the 
photographs, subject identification will be blinded. Additionally, the photography manual 
will include detailed procedures on photograph masking is to be done hence assuring 
protection of subject privacy. 
3.5.6.29 Prior Biologics  
Information pertaining to prior biologics use will be collected. 
3.5.6.30 Prior/Concomitant Medications 
Information pertaining to all medication use (including prescription, over-the-counter, 
supplements, vitamins and minerals) will be collected for the period of at least 30 days prior 
to the Screening Visit (Visit 1) and throughout the study. For medications excluded for a 
longer than a 30-day period, as described in Section 3.5.4.1, the timeframe for collecting this 
information will be extended to cover at least the exclusion period. 
 
 
 
 
 
 
 
 
 
 


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n
 
 
3.5.6.32 Pharmacokinetic Procedures 
3.5.6.32.1 BLOOD SAMPLES FOR PHARMACOKINETIC ASSESSMENTS 
Blood samples for the quantification of plasma JTE-051 will be collected, according to the 
schedules summarized in Table 1 and Figure 2. Trough PK blood samples will be collected in 
the fasted state at pre-specified study visits.  
At each study visit during the treatment period (i.e., Visits 2 through 6), the actual dosing 
date and time, as well as the sample collection date and time will be documented for PK data 
analysis (see Figure 2). Refer to the laboratory manual for specific instructions for the 
collection, processing, storing and shipping of blood samples for PK assessments. 
3.5.6.32.2 ANALYSIS OF JTE-051 IN PLASMA 
JTE-051 in plasma will be analyzed using a validated high-performance liquid 
chromatography/tandem mass spectrometry (LC-MS/MS) method. 
The laboratory performing the JTE-051 plasma concentration assessments will be unblinded 
to facilitate analysis of only the samples from the JTE-051-treated subjects. Plasma samples 
from placebo subjects may be analyzed as needed. 


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3.5.7 Clinical Institutions and Laboratories 
This study will be conducted by: 


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3.6 Adverse Events 
3.6.1 Safety Definitions 
Akros complies with the following International Council for Harmonization of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) AE definitions: 
Adverse Event: An AE is any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily 
have a causal relationship with this treatment. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medical (investigational) product, whether or not related to the 
medical (investigational) product.  
Serious Adverse Event: As provided by the ICH criteria, an SAE is any adverse drug 
experience occurring at any dose that results in any of the following outcomes: 
• death 
• a life-threatening adverse drug experience 
• inpatient hospitalization or prolongation of existing hospitalization 
• a persistent or significant disability/incapacity 
• a congenital anomaly/birth defect 
• other important medical event 
Note: Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject or may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 
Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in hospitalization, or the development of drug dependency or drug abuse.  
Adverse Reaction: All noxious and unintended responses to an investigational medicinal 
product (IMP) related to any dose administered. 
Note: The phrase "responses to a medicinal product" means that a causal relationship 
between the medicinal product and an adverse event is at least a reasonable possibility, 
i.e., the relationship cannot be ruled out. 
Unexpected Adverse Drug Reaction: An adverse reaction, the nature (specificity) or 
severity of which is not consistent with the applicable product information (e.g., IB). 
Death: Death represents an outcome and a SAE criterion, not an event term. The medical 
condition with the fatal outcome should be reported unless the cause of death is unknown, in 
which case the term “Death” is acceptable. 
Inpatient Hospitalization/Prolongation of Hospitalization: Any admission (even if less 
than 24 hours) to a healthcare facility. Admission also includes transfer within the hospital to 
an acute/intensive care unit (e.g., medical floor to the coronary care unit). Initial and 
prolonged hospitalizations that do not meet this SAE criterion include those due to social 
and/or convenience reasons (e.g., lack of personal care at home, unable to transfer to 
non-acute facility), admission to rehabilitation/hospice/skilled nursing facilities, emergency 


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room visits, same-day/outpatient/ambulatory procedures, and those for pre-planned, elective 
procedures for a pre-existing condition that did not worsen after the informed consent has 
been signed (no AE present). However, if the hospitalization was prolonged due to a 
complication of a pre-existing condition, the complication (diagnosis of same) would qualify 
as an SAE. 
Disability: A substantial disruption of a person’s ability to conduct normal life functions. 
Life-threatening: Any adverse drug experience that places the patient or subject, in the view 
of the Investigator, at immediate risk of death from the reaction as it occurred, i.e., it does not 
include a reaction that had it occurred in a more severe form, might have caused death. 
Physical Examination, 
n, Vital Signs, Laboratory Test and 
ECG Abnormalities: Any abnormalities fulfilling the criteria for an SAE should be reported 
as such, in addition to being recorded as an AE in the CRF. Any abnormal vital sign, physical 
(
 finding or laboratory/ECG result which is clinically significant 
(i.e., meets one or more of the following conditions) should be recorded as a single diagnosis 
on the AE page in the CRF: 
• Accompanied by clinical symptoms 
• Leads to permanent discontinuation of study drug 
• Requires a change in concomitant therapy (e.g., addition of, interruption of, 
discontinuation of, or any other change in a concomitant medication, therapy or 
treatment). 
This does not apply to abnormal vital signs, physical finding or laboratory/ECG results that 
do not meet the clinical significance criteria or those which are a result of an AE which has 
already been reported. 
Pre-existing conditions that are detected at the Screening Visit (Visit 1), including 
abnormalities in ECG, physical examination, n
n, vital signs and 
laboratory tests, are considered to be medical history
3.6.2 Assessing Adverse Events 
When completing appropriate forms for reporting the AE, the Investigator will be asked to 
assess the AE as follows: 
Seriousness of Adverse Event: 
• Serious: The AE meets a criterion of the SAE definition. 
• Not Serious: The AE does not meet a criterion of the SAE definition. 
Severity of Adverse Event:  
• Mild: No interference with functioning. 
• Moderate: No significant interference with functioning. 
• Severe: Significant interference with functioning. 


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Relationship of Adverse Event (Causality):  
The Investigator’s causality assessment is the determination whether there is a reasonable 
possibility that the IMP caused or contributed to the adverse event. Generally, the facts 
(evidence) or arguments to suggest causal relationship should be documented. Factors to be 
taken into consideration when assessing causality include: subject’s underlying and 
pre-existing conditions, prior/concomitant medications, timing of onset relative to study drug 
administration, the known PK characteristics of JTE-051, the currently-known safety profile 
of JTE-051, known class effects of similar MOA drugs and any other information that is 
considered relevant by the Investigator. 
Akros Pharma Inc. evaluates the relationship of an AE to the study drug using the following 
three categories: 
• Not Related  
• Possibly Related 
• Related 
Action Taken with Regard to Study Drug: 
Akros Pharma Inc. evaluates the action taken with the treatment product and/or interacting 
product using the following four definitions: 
• Dose Not Changed: The subject was on treatment with the study drug when the AE 
occurred, and the study drug dosing was maintained at the same dose level 
• Drug Interrupted: The subject was on treatment with the study drug when the AE 
occurred, and the study drug dosing was temporarily discontinued and then re-started 
• Drug Withdrawn: The subject was on treatment with the study drug when the AE 
occurred, and the study drug dosing was permanently discontinued  
• Not Applicable: The subject was not receiving treatment with the study drug when the 
AE occurred (i.e., AE occurred before the first study drug administration or after the last 
study drug administration) 
Other Action Taken:  
• None 
• Additional Treatment Given for the AE 
• Therapeutic/ Diagnostic Procedure 
• Other (including discontinuation/reduction of a concomitant medication due to the AE)  
Outcome to Date: 
• Not Recovered/Not Resolved: The subject has not yet recovered from the AE; the event 
has not improved (follow-up of all serious AEs will be continued until the overall clinical 
outcome has been ascertained). 
• Recovering/Resolving: The subject has not yet recovered from the AE, however, the 
event is improving (follow-up of all serious AEs will be continued until the overall 
clinical outcome has been ascertained).  
• Recovered/Resolved: The subject recovered from the AE with no sequelae. 
• Recovered/Resolved with Sequelae: The subject recovered from the AE with sequelae. 
• Fatal: The subject’s death was a result of the AE.  


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3.6.3 Reporting Adverse Events  
Adverse Events Reporting  
Adverse events occurring (initial occurrence or a worsening of a pre-existing condition) after 
the informed consent has been signed and up to 4 weeks (28 days) after the last dose of study 
drug will be reported and included in the study database. However, pre-existing conditions 
detected as part of the screening procedures should be documented as medical history. 
Worsening of the underlying condition (i.e., plaque psoriasis) or signs/symptoms associated 
with this condition should not be reported as an AE unless they meet at least one serious 
criterion; in such case when they would be reported as both an AE and an SAE. Adverse 
events will be reported on the AE CRF page.  
Serious Adverse Event Reporting 
Reporting by Investigators 
Detailed instruction regarding SAE reporting will be provided in the appropriate documents 
outside of this protocol. A brief, non-all-inclusive summary is provided below. 
Any SAE experienced by a study subject after signing the informed consent up to 28 days 
after the last dose of study drug will be reported to the Sponsor or designee. Additionally, 
SAEs that occur after this period will also be reported to the Sponsor or designee if the 
Investigator considers the SAE possibly related or related to the study drug. 
Serious adverse events (both initial reports and follow-up information) must be reported to 
the Sponsor or designee within 24 hours of the Investigator’s (site’s) awareness or 
notification of the event. 
The Investigators should make every effort to provide complete information when reporting 
the SAE (both for initial reports, as well as for follow-ups).  
The Investigator must continue to follow the subject until the SAE has subsided, the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the 
subject dies. Within 24 hours of receipt of follow-up information, the Investigator must 
submit it to the Sponsor or designee. 
The Investigator is also required to submit SAE reports to the IRB/IEC in accordance with 
local requirements. All investigators involved in studies using the same IMP will receive any 
Suspected Unexpected Serious Adverse Reaction (SUSAR) reports for onward submission to 
their local IRB/IEC as required. All reports sent to investigators will be blinded. 
Reporting by the Sponsor 
Competent authorities and IRBs/IECs will be informed by the Sponsor or designee of 
SUSARs according to the local requirements. Additionally, all SUSARs will be reported by 
the Sponsor or designee into the EudraVigilance system, as appropriate. Cases will be 
unblinded by designated personnel for reporting purposes as required. 
Exposure in Utero Reporting: 
If a female subject becomes pregnant or the female partner of a male subject participating in 
the study becomes pregnant after the subject receives the first dose of study drug, or within 


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28 days of discontinuing study drug, the Investigator should report the pregnancy to the 
Sponsor or designee within 24 hours of being notified.  
The subject/partner should be followed by the Investigator until completion of the pregnancy. 
If the pregnancy ends for any reason before the anticipated date, the Investigator should 
notify the Sponsor or designee. At the completion of the pregnancy, the Investigator will 
document the outcome of the pregnancy. If the outcome of the pregnancy meets the criteria 
for immediate classification as an SAE (i.e., spontaneous abortion, stillbirth, neonatal death, 
or congenital anomaly), the Investigator should follow the procedures for reporting an SAE 
as described above. 
Overdose Reporting: 
An overdose is a significant variation from the recommended/scheduled dosage for a 
product. For the purposes of this study, overdose is defined by any confirmed use of blinded 
study medication of more than four tablets once a day. If such situations occur, the 
Investigator should provide additional training to the subject on study drug dosing 
instructions and emphasize the importance of compliance. Currently there is no known 
antidote to JTE-051, thus appropriate symptomatic and/or supportive care is to be provided at 
the Investigator’s discretion, as needed. The subject’s continued eligibility will be left to the 
judgment of the Investigator. 
Information on overdoses in subjects is collected by the Sponsor or designee. Should a 
subject experience an overdose during the course of the study, the investigator or qualified 
designee must report the overdose as soon as possible, but not later than the timeframe 
requested by the Sponsor or designee after the investigator or qualified designee first 
becomes aware of the overdose. Instructions will be provided on how to collect this 
information. 
3.7 Identification of Treatments  
3.7.1 Method of Assigning Subjects to Treatment Groups 
After subject signs the informed consent, each site will assign potential study subjects an 
eight-character subject number. This number will consist of a four-digit site number (with the 
first two digits representing the country-specific number and the next two digits representing 
the site-specific number) and a three-digit subject number assigned in a sequential manner. 
The hyphen between the site and subject number will account for the eighth character. This 
number will represent the subject’s identifier throughout the study. Following confirmation 
of eligibility at Visit 2, the Interactive Web Response System (IWRS) will be contacted by 
the site and it will assign the subject a four-digit randomization number that will correspond 
to a randomly assigned treatment group. 
3.7.2 Identity of Investigational Products  
E
 
 


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3.7.3 Storage and Handling Procedures 
The JTE-051 and placebo tablets should be stored at room temperature between 20 and 25°C 
(United States Pharmacopeia [USP]) and in a secure location with restricted access.  
3.7.4 Clinical Supplies Packaging 
Each site will receive a supply of double-blind study drug packaged as blister cards 
corresponding to 8 days of QD dosing. Each blister card will contain a total of 32 JTE-051 
tablets.  
Study drug blister cards may be labeled with the following information, as appropriate: 
• 
Sponsor identity and protocol number 
• 
Card number 
• 
Dosing instructions 
• 
Spaces for site personnel to add subject number and subject initials 
• 
Spaces for site personnel to add visit number, site number and Investigator name 
• 
Spaces for site personnel to add the card identifier, as appropriate 
• 
Quantity and identity of contents 
• 
Lot number and storage conditions 
• 
Expiration date 
• 
For investigational use only statement 
The planned blister card allocation of tablets for each dose, broken down by treatment group, 
is provided below. 
3.7.5 Administration of Study Drug 
During the Treatment Period, beginning on the day of Visit 2, subjects will self-administer 
one dose of study drug (4 tablets) daily for 12 weeks. Study drug will be taken QD in the 
Treatment 
Group 
Tablet 1 
Tablet 2 
Tablet 3 
Tablet 4 
JTE-051 50 mg 
JTE-051 50 mg 
JTE-051 Placebo 
JTE-051 Placebo 
JTE-051 Placebo 
JTE-051 100 mg 
JTE-051 50 mg 
JTE-051 50 mg 
JTE-051 Placebo 
JTE-051 Placebo 
JTE-051 150 mg 
JTE-051 50 mg 
JTE-051 50 mg 
JTE-051 50 mg 
JTE-051 Placebo 
JTE-051 200 mg 
JTE-051 50 mg 
JTE-051 50 mg 
JTE-051 50 mg 
JTE-051 50 mg 
Placebo 
JTE-051 Placebo 
JTE-051 Placebo 
JTE-051 Placebo 
JTE-051 Placebo 


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morning, regardless of meals. On the scheduled study visit days, subjects should not take 
study drug prior to arriving to the site. At the site, study drug will be administered from the 
previously supplied blister card, if available, after all study procedures have been completed 
(except for appropriate PK samples collection procedures as discussed in Figure 2). If no 
tablets from the previously supplied blister cards are available, then the subject should dose 
from the new blister card supplied at that visit. 
Randomized subjects will receive three study drug blister cards at Visits 2 and two study 
drug blister cards at Visit 3. Subjects will receive four blister cards each on Visits 4 and 5. 
The subjects will be instructed to use the blister cards on a first-in/first-out basis and to return 
all study drug blister cards from the former visit for accountability and compliance 
assessment at Visits 3, 4, 5 and 6 for accountability and compliance assessment. Following 
completion of accountability and compliance assessments, any unused blister card or a 
partially used blister card with the study drug available will be returned to the subject. At 
Visit 6, study drug will not be dispensed. 
In the event that the subject does not take the study drug on a given day during the Treatment 
Period, the subject should not take more than the daily dosage on the following treatment day. 
3.7.6 Management of Clinical Supplies 
The Investigator will have responsibility for the control and proper distribution of all study 
drug (including any investigational product or reference product) in accordance with this 
protocol. The Investigator is responsible for ensuring that all study drug will be stored at the 
site at recommended storage temperatures and conditions, in a secured area, free of 
environmental extremes, with restricted access. The Investigator also ensures that all study 
drug will be dispensed only to study subjects who have provided written informed consent 
and have met all entry criteria. 
Study drug accountability will be performed by the Investigator or designee at each study 
visit during the Treatment Period, according to the schedule of procedures presented in 
Table 1. Study drug compliance will be assessed and documented per the Good Clinical 
Practices (GCP). 
3.7.7 Randomization 
Approximately 85 eligible subjects with moderate to severe plaque psoriasis will be 
randomized into this study. Subjects will be randomized in a 1:1:1:1:1 ratio (17 subjects per 
treatment group) to receive JTE-051 50 mg, JTE-051 100 mg, JTE-051 150 mg, 
JTE-051 200 mg or placebo QD. Randomization will be stratified based on prior exposure of 
subjects to biologic therapy (i.e., biologic treatment-naïve vs. biologic treatment­experienced 
subjects). 
An IWRS will be employed for the randomization activities. It will use a stratified 
randomization algorithm that takes into account the strata specified above. 
The randomization code will be controlled by an unblinded member of the Sponsor or 
designee who will provide the randomization code to select laboratories, see Section 3.7.8. 


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3.7.8 Blinding  
This study is double-blind (i.e., the treatment assigned to each subject will not be disclosed to 
the Sponsor members or designees involved in the study, study staff at the site or to the 
subject). The JTE-051 50 mg tablets, as well as the placebo tablets will be supplied as 
unbranded tablets which are identical in appearance.  
The laboratory performing the JTE-051 plasma concentration assessments will be unblinded 
to facilitate analysis of only the samples from the JTE-051-treated subjects. Plasma samples 
from placebo-treated subjects may be analyzed as needed (see Section 3.5.6.32.2). 
3.7.9 Breaking the Blind 
The study drug code may be broken by the Investigator for a particular subject only in the 
event of a serious adverse experience, which the Investigator feels cannot be adequately 
treated without knowing the identity of the study drug by using the IWRS. Every effort must 
be made to contact the Sponsor’s Medical Monitor prior to breaking the code. If this is not 
possible and the situation is an emergency, the Investigator may break the blind to identify 
the treatment assignment for the specific subject only and must contact the Sponsor’s 
Medical Monitor as soon as possible thereafter. The Sponsor may also elect to break the 
blind for cause. If the blind is broken, appropriate documentation should be completed as 
soon as possible. 
Additionally, breaking of the blind may be performed by sponsor designated independent 
member not involved in the clinical conduct of the study for regulatory reporting purposes, as 
appropriate.  
3.8 Statistical Methods 
This section provides an abbreviated statistical analysis plan (SAP) for the efficacy, safety 
and PK. A formal SAP will be developed at a later time. Statistical issues not addressed in 
this section may be developed in the formal SAP. The plans outlined in this section may be 
modified in the SAP; however, any major modifications of the primary endpoint definition 
and/or its analysis may also be reflected in a protocol amendment, as appropriate. Other 
deviations to the SAP will be discussed in the study report. 
3.8.1 Subject Population for Analysis 
3.8.1.1 Randomized Population 
The randomized population consists of all subjects who are randomized at Visit 2 to one of 
the five treatment groups: JTE-051 50 mg QD, JTE-051 100 mg QD, JTE-051 150 mg QD, 
JTE-051 200 mg QD and matching placebo QD. 
3.8.1.2 Safety Population 
Safety population consists of the randomized subjects who receive at least one dose of the 
study drug and have at least one post-randomization safety data.  


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3.8.1.3 Intent-To-Treat (ITT) Population 
The ITT population consists of the randomized subjects who receive at least one dose of the 
study drug per randomization and have at least one post-randomization efficacy data. 
3.8.1.4 Per Protocol (PP) Population 
The PP population is a subset of the ITT population in which subjects do not have any major 
protocol deviations. A pre-analysis meeting will take place after all data have been entered 
into the database and cleaned, but before the release of the randomization code, to identify 
the PP population. The decisions made to select the PP population will be documented. 
3.8.1.5 Pharmacokinetic (PK) Population 
The PK population consists of the randomized subjects who receive at least one dose of 
JTE­051 and have at least one usable JTE-051 plasma concentration measurement. 
3.8.1.6 Sample Size 
Approximately 85 eligible subjects (17 subjects in each treatment group) will be randomized 
into the treatment period of this study. 
 


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3.8.2 Interim Analysis 
No interim analysis is planned in this study. 


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3.8.3 Efficacy Analyses 
The ITT population will be used for all efficacy data analysis. The analysis of the primary 
efficacy parameter will be repeated on the PP population if it excludes 20% or more of the 
subjects from the ITT population. Additional efficacy analyses using the PP population may 
be performed if deemed appropriate. 
3.8.3.1 Efficacy Parameters 
The primary efficacy parameter is the proportion of subjects achieving PASI 75 at EOT. 
The secondary efficacy parameters are (evaluated at Weeks 2, 4, 8, 12 and 16, unless 
otherwise stated): 
• Percent change from baseline in PASI score; 
• Proportions of subjects achieving PASI 50, PASI 75, PASI 90 and PASI 100; 
• Proportion of subjects achieving a sPGA score of 0 or 1; 
• Change from baseline in sPGA score; 
• Percent change from baseline in the psoriasis affected BSA; 
• Change from baseline in Skindex-16; 
3.8.3.2 Efficacy Data Analysis 
For the purpose of efficacy analysis, the EOT value is defined as the last value taken during 
the double-blind treatment period after the first dose of study drug, without any treatment 
intervention.  
Conventional statistical evaluations for efficacy parameters will also be conducted as 
described below: 
For the primary efficacy parameter (PASI 75 at EOT), the Fisher’s exact test will be used to 
compare each JTE-051 dose group with placebo. 


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For dichotomous secondary efficacy parameters, similar analyses as the primary efficacy 
parameter will be used by time point, 
 
 
 
For continuous efficacy parameter analysis with multiple time points, a mixed effect model 
will be employed. It includes fixed effects for treatment, time, treatment by time interaction, 
the stratification factor and the appropriate baseline and subject as the random effect. The 
appropriate baseline will be the parameter from which the efficacy parameter is derived, 
e.g., PASI score at Week 0 for the analysis of percent change from baseline in PASI score. 
The treatment effect of each JTE-051 dose group relative to placebo at the same time point 
will be estimated. A linear trend test at each time point will be computed using appropriate 
linear contrast. 
All analyses will be performed two-sided at the 5% significance level. No formal multiple 
comparison adjustment will be made, therefore, results should be interpreted with the 
multiplicity in mind. The estimated treatment effect (relative to placebo) from the model, 
along with a two-sided 95% CI and p-value, will be tabulated where appropriate. The 
Newcombe’s CI of the rate difference between JTE-051 dose and placebo will be computed 
when performing the Fisher’s exact test. Graphical presentations of the treatment profile may 
be depicted. Sensitivity analysis, model fit assessment may be conducted and data 
transformation may be employed if appropriate. 
Descriptive statistics of efficacy parameters over time will be presented by treatment. It will 
include the number of subjects (N), arithmetic mean, standard deviation (SD), median, 
minimum and maximum for continuous parameters, and in frequency tabulation form for 
dichotomous parameters. 


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3.8.3.3 Treatment by Center Effect 
The randomization of this study is stratified by prior exposure to biologic therapy. Center 
effect is not considered due to the expectation that many centers will be used and only a 
small number of subjects will be enrolled in most centers. 
3.8.3.4 Treatment by Baseline Covariate Effect 
The treatment-by-baseline effect is not considered, however the baseline will be included in 
the respective parametric analysis model of the efficacy parameters where appropriate.  
3.8.3.5 Subgroup Analysis 
Subgroup analyses may be performed if appropriate. 
3.8.3.6 Handling of Dropouts or Missing Data 
There may be missing data intermittently (i.e., a missing visit or subject dropout). For 
dichotomous efficacy parameters analysis by time point, subjects with missing data will not 
be included in the analysis. For analysis with multiple time points, any missing data will be 
imputed using the last observation carried forward (LOCF) method except for subjects who 
withdraw for reasons related to treatment. In the latter case, any value after withdrawal will 


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be imputed as treatment failure. For parameters analyzed both by time point and with 
multiple time points, these two approaches would strengthen the findings when they are 
similar. 
For continuous efficacy parameters, no imputation will be employed. This is because the 
mixed effect model gives valid estimates if the missing data mechanism is “missing at 
random”, a common assumption made as the first approach for analysis. 
For the sensitivity analysis of the primary efficacy parameter, i.e., PASI 75 at EOT, missing 
data may be imputed by all possible combinations of success and failure. The robustness of 
the finding can be evaluated using the tipping point analysis based on the plausibility of the 
imputed values. 
Other missing data imputation methods may be employed for additional sensitivity analysis if 
deemed necessary. 
3.8.4 Safety Analyses 
The safety population will be used for the safety data analysis unless otherwise stated. 
3.8.4.1 Safety Parameters 
The safety parameters are: 
• Adverse events 
• Clinical laboratory safety tests  
• Vital signs, ECG parameters 
3.8.4.2 Safety Data Analysis 
Descriptive statistics of vital signs, ECG parameters, and clinical laboratory data will be 
presented by treatment in tabular form with N, arithmetic mean, SD, median, minimum and 
maximum, or in frequency tabulation form as appropriate. For continuous parameters, change 
from baseline will be summarized by treatment as appropriate. Potentially clinically 
significant values for vital signs, ECG and laboratory data will be flagged in data listings and 
may be summarized as appropriate. 
All safety data will be presented in the data listings, and will be flagged for events of interest 
(e.g., out of range laboratory data) as appropriate. 
Adverse events will be coded using the current version of Medical Dictionary for Regulatory 
Activities (MedDRA), and will be summarized by SOC and preferred term. 
Other safety parameters will be summarized as appropriate. 
3.8.5 Pharmacokinetic Analyses 
The PK population will be used for the PK data analysis unless otherwise stated. 
3.8.5.1 Trough Concentration 
Trough (pre-dose) plasma concentrations of JTE-051 at Weeks 2, 4, 8 and 12 will be 
summarized in terms of the number of subjects, arithmetic mean, standard deviation, 


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coefficient of variation (CV%), median, minimum and maximum by treatment and visit. The 
relationship between the dose and trough plasma concentrations of JTE-051 will also be 
assessed. 
3.8.5.2 Exposure-Response Relationship 
The relationship between the exposure to JTE-051 (e.g., trough concentration of JTE-051) 
and response (e.g., the proportion of subjects achieving PASI 75 at EOT) may be explored. 
3.8.5.3 Population Pharmacokinetic Analysis 
Preliminary population PK analysis will be performed using plasma concentration of 
JTE­051. Population estimates of PK parameters of JTE-051 such as the apparent oral 
clearance of drug following extravascular administration (CL_F) and apparent volume of 
distribution following extravascular administration (V_F) will be estimated and inter-subject 
variability of these parameters will be characterized. The effect of intrinsic/extrinsic factors 
(e.g., age, body weight, gender, race, use of concomitant medications) on the 
pharmacokinetics of JTE-051 will be evaluated. Other PK parameters will be determined and 
reported as deemed appropriate. The analysis may be carried out using the data combined 
with plasma concentration of JTE-051 obtained in other clinical studies. The population 
pharmacokinetic analysis plan and the report may be prepared separately when appropriate. 
3.9 Quality Control and Quality Assurance 
This study will be conducted in compliance with the protocol, GCP as defined by the US 
Code of Federal Regulations (CFR) 21 Parts 50, 56 and 312, Sponsor/designee policies and 
procedures and all applicable local and national regulations. 
The following steps will be taken to ensure the accuracy, consistency, completeness, and 
reliability of the data: 
a) Routine site monitoring; 
b) CRF review against source documents; 
c) Data management quality control checks; 
d) Statistical quality control checks; 
e) Continuous data acquisition and cleaning; and 
f) Quality control of final report. 
A representative from the Sponsor and/or authorized representatives may conduct periodic 
audits of the sites and study processes, including, but not limited to, the clinical database and 
the final report. The study may also be subject to inspection by regulatory authorities. The 
Investigator hereby agrees to allow access to required subject records and other 
documentation and facilities related to the review and conduct of the study. 
4 INVESTIGATOR OBLIGATIONS 
4.1 Institutional Review/Independent Ethics Committee  
An Investigator shall ensure that an IRB/IEC that complies with the requirements set forth in 
the US CFR 21 Part 56 or in the applicable local regulations for countries outside US, as 
applicable, will be responsible for the initial and continuing review and approval of the 


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proposed clinical study. The Investigator shall also assure that he or she will promptly report 
to the IRB/IEC all changes in the research activity and all unanticipated problems involving 
risk to human subjects or others, and that he or she will not make any changes in the research 
without IRB/IEC approval, except where necessary to eliminate apparent immediate hazards 
to human subjects. 
All advertisements used in conjunction with this study must be reviewed and approved by the 
Sponsor or designee prior to use and the IRB/IEC, if applicable. The IRB/IEC’s approval will 
be documented in writing and sent to the Investigator. The Investigator will forward a copy 
of the IRB/IEC approval document to the Sponsor or designee.  
The Investigator will not begin the study until the Sponsor or designee has authorized release 
of investigational drug product. 
Any amendments to the protocol must be approved in writing by the IRB/IEC prior to 
implementation by the Investigator. However, any change to the protocol to eliminate an 
apparent immediate hazard to the subjects may be implemented immediately, provided that 
the IRB/IEC is subsequently notified in accordance with the US 21 CFR Part 56.104 (c) or 
the applicable regulations in countries outside US. 
The Investigator will also provide the IRB/IEC with a current copy of the IB at the start of 
the study, as well as an updated version of each if revised during the study. 
A progress report will be submitted by the Investigator to the IRB/IEC at intervals 
established by the IRB/IEC. The Investigator will retain a copy of this report in the 
Investigator’s Documentation File. After completion or termination of the study, the 
Investigator will submit a final documentation to the IRB/IEC. A copy of all reports will be 
sent to the Sponsor or designee. 
4.2 Subject Consent 
In obtaining and documenting informed consent, the Investigator should comply with the 
applicable regulatory requirement(s), i.e., US 21 CFR Part 50 in the US and any applicable 
regulations in countries outside the US, and should adhere to GCP. Prior to the beginning of 
the trial, the Investigator should have the IRB/IEC written approval of the written informed 
consent form and any other written information to be provided to subjects. 
The written informed consent form and any other written information to be provided to 
subjects must be revised whenever important new information becomes available that may be 
relevant to the subject’s consent. Any revised written informed consent form, and written 
information must receive the IRB/IEC approval in advance of use. The subject must be 
informed in a timely manner if new information becomes available that may be relevant to 
the subject’s willingness to continue participation in the trial. The communication of this 
information should be documented. 
The Investigator, or a person designated by the Investigator, should fully inform the subject 
of all pertinent aspects of the trial including the written information and the approval by the 
IRB/IEC. A copy shall be given to the person signing the form. 


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4.3 Data Collection 
It is the Investigator’s responsibility to ensure that data are collected and reported according 
to the study protocol. The Investigator will ensure the accuracy, completeness and timeliness 
of the data reported on the CRF and in all required reports.  
Additionally, laboratory, photography and itch data may be received by Clinical Data 
Management from the appropriate Clinical Laboratory in electronic format. These data files 
may be merged with the clinical database. 
4.3.1 Case Report Forms 
Electronic CRFs will be produced according to protocol requirements, and access/training 
will be provided to the site in order for the research staff to record the data obtained on each 
subject during the study.  
The CRFs must be completed for all subjects who have signed informed consent for the 
study and will be reviewed by the Clinical Monitor and verified against source documents. 
The CRFs must be kept up­to-date so that they always reflect the latest observations on the 
subjects enrolled in the study. All records should be kept in conformance to applicable 
national and local laws and regulations. 
4.3.2 Source Documents 
It is the responsibility of the Investigator to collect and record all study data on source 
documents. The Investigator must provide access to source data/documents for study-related 
monitoring, audits, IRB/IEC review and regulatory inspection. 
4.4 Adherence to Protocol 
By signing the Signature Page of this protocol, the Investigator confirms in writing that 
he/she has read, understands and will strictly adhere to the study protocol. This study will be 
conducted in accordance with GCP regulations. Additional information regarding 
management of protocol amendments can be found in Section 5.2. 
4.5 Reporting Adverse Events 
For details regarding AE and SAE reporting, see Section 3.6.3. 
4.6 Investigator’s Final Report 
Upon completion of the study, the Investigator will provide the Sponsor or designee with a 
copy of the summary of the study’s outcome provided to the IRB/IEC. 
4.7 Records Retention 
An Investigator is required to maintain adequate records of the disposition of the drug, 
including dates, quantity and use by subjects. When the investigation is terminated, 
suspended, discontinued, or completed, the Investigator shall return the unused supplies of 
the drug to the sponsor, or otherwise provide for disposition of the unused supplies of the 
drug under the US 21 CFR Part 312.59 and all applicable local regulations. 


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An Investigator shall retain records required to be maintained under this part for a period of 
two years following the date a marketing application is approved for the drug for the 
indication for which it is being investigated; or, if no application is to be filed or if the 
application is not approved for such indication, until two years after the investigation is 
discontinued and the FDA is notified. 
For sites in Canada, the Investigator shall retain records required to be maintained under this 
part for a period of twenty-five years following completion of the clinical trial in accordance 
with the local regulations. 
The Sponsor or designee should inform the Investigator(s)/institution(s) in writing of the 
need for record retention and should notify the Investigator(s)/institution(s) in writing when 
the trial related records are no longer needed. 
Custody of the records may be transferred to another responsible party, acceptable to the 
Sponsor, who agrees to abide by the retention policies. Written notice of transfer must be 
submitted to the Sponsor or designee. The Investigator must contact, and obtain prior written 
permission of the Sponsor prior to disposing of or transferring any study records. 
4.8 Confidentiality 
The Investigator, Medical Monitor, the Sponsor and its representatives, agree to protect the 
privacy and confidentiality of the protected health information in accordance with applicable 
laws and regulations.  
Subject medical information obtained by the study is confidential and disclosure to third 
parties other than those noted below is prohibited unless required by law. The Investigator 
shall retain all such information, and any other information designated by the Sponsor as 
confidential, or is otherwise of reasonably confidential nature, in confidence and shall not use 
such information for any purpose other than the performance of obligations pursuant to the 
agreement with the Sponsor and designated affiliates or contractors, as the case may be, 
without prior written authorization from the Sponsor. 
At the subject’s request, medical information may be given to his or her personal physician 
or other appropriate medical personnel responsible for his or her welfare. 
Data generated by this study must be available for inspection on request by representatives of 
regulatory authorities, the Sponsor or designee, and the IRB(s)/IEC(s) if appropriate. 
4.9 Publications 
The Investigator agrees that all data, calculations, interpretations, opinions and 
recommendations regarding the study shall be the sole and exclusive property of the Sponsor, 
and that the Sponsor may make any use thereof at its discretion without obligation to 
Investigator. The Investigator agrees to consider the results as information subject to 
confidential and use restrictions. 
In the event that the study results are published in the scientific literature by the Sponsor, 
acknowledgment will be made to the Investigator(s) in the accepted style, as appropriate. The 
names of the Investigators or their representatives shall not be used by the Sponsor in 


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publications, for advertising, for other commercial purposes, or otherwise, without 
appropriate written permission, unless required by law or government regulation. 
Individual study center manuscript(s) for publication, text for talks, abstracts of papers, 
poster presentations, and similar material will be submitted to the Sponsor for review and 
comment prior to publication or disclosure. In order to ensure that the Sponsor will be able to 
make comments and suggestions where pertinent, material for public dissemination will be 
submitted to the Sponsor for review at least sixty (60) days prior to submission for 
publication, public dissemination, or review by a third party committee. The Sponsor will 
have sixty (60) days from receipt of such information to review and comment on and discuss 
the contents thereof with the Investigator. If the Sponsor requests, the Investigator will 
remove any and all confidential information (other than study results) prior to submitting or 
presenting the materials. Upon the Sponsor’s request, the Investigator will delay submitting 
or presenting the materials for a further sixty (60) days to permit the Sponsor to take 
necessary actions to protect its confidential information, including the filing of patent 
applications thereon. 
5 STUDY MANAGEMENT  
5.1 Monitoring 
Monitoring visits will be conducted by the Sponsor or designee according to applicable 
regulations and guidelines for GCP. The Investigator will permit the Sponsor and/or 
designated representative(s) to make regular site visits during the study. The frequency of 
monitoring visits will be agreed upon by the Sponsor and/or designee. At each visit, the 
Investigator and staff will be expected to cooperate with the Sponsor or designee for the 
review and verification of protocol compliance, AE reporting, CRFs, source documents, 
clinical supplies and inventory records, and any additional records as may have been 
previously arranged between the Investigator and Akros or designated representative(s). 
The Investigator and/or other designated study personnel are expected to contact the monitor 
of the Sponsor or designee as needed regarding study concerns and/or questions. 
5.2 Management of Protocol Amendments and Deviations 
With the exception of emergency situations, implementation of any change in the protocol 
that affects the safety of the subjects, the scope of the investigation, or the scientific quality 
of the study will not be permitted until the Sponsor and the Investigator have approved the 
protocol amendment and the IRB/IEC responsible for review and approval of the study has 
reviewed and approved the protocol change. 
Implementation of changes that do not affect the safety of the subjects, the scope of the 
investigation, or the scientific quality of the study cannot be made until the protocol changes 
are reviewed and approved by Akros and the Investigator. The IRB/IEC must be notified of 
these protocol changes. 
The Investigator will not deviate from the protocol without prior written approval from the 
Sponsor or designee. 


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5.3 Study Termination 
The study may be terminated at any time at the request of the Sponsor or the Investigator 
with proper and timely notification of all parties concerned. The IRB/IEC will be informed 
promptly and reasons for the termination or suspension will be provided by the Investigator, 
as specified by the applicable regulatory requirements. The study can be considered complete 
and/or terminated after the Sponsor or designee has received the following data and 
materials: 
• Laboratory findings, clinical data, and all special test results from screening through the 
end of the follow-up 
• CRFs properly completed by appropriate study personnel (including correctly answered 
and closed system or manually-generated edit checks) and signed by the Investigator 
• Completed Drug Accountability Records 
• Statement of outcome for each SAE reported 
• Approval/notification of protocols and protocol amendments from IRB/IEC as well as 
relevant health authorities (if applicable) 
5.4 Sponsor’s Final Report 
A final report will be prepared by the Sponsor or a designee at the conclusion of this clinical 
study. 


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6 REFERENCES 
1. Valenzuela F, Paul C, Mallbris L, Tan H, Papacharalambous J, Valdez H, et al. 
Tofacitinib versus etanercept or placebo in patients with moderate to severe chronic 
plaque psoriasis: patient-reported outcomes from a phase 3 study. J Eur Acad Dermatol 
Venereol. 2016 Oct;30(10):1753-9. 
2. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the 
United States. J Am Acad Dermatol. 2014 Mar;70(3):512-6. 
3. Huntley C. Psoriasis Epidemiology (Report Reference:DMKC0144470) Datamonitor 
Healthcare. Published on 22/09/2015:1-26. 
4. Kubota K, Kamijima Y, Sato T, Ooba N, Koide D, Iizuka H, et al. Epidemiology of 
psoriasis and palmoplantar pustulosis: a nationwide study using the Japanese national 
claims database. BMJ Open. 2015 Jan 14;5(1):e006450. 
5. Parisi R, Symmons DP, Griffiths CE, Ashcroft DM. Global epidemiology of psoriasis: a 
systematic 
review 
of 
incidence 
and 
prevalence. 
J 
Invest 
Dermatol. 
2013 Feb;133(2):377­85. 
6. Rapp SR, Feldman SR, Exum ML, Fleischer AB Jr, Reboussin DM. Psoriasis causes as 
much disability as other major medical diseases. J Am Acad Dermatol. 1999;41:401-7. 
7. Büchau AS, Gallo RL. Innate immunity and antimicrobial defense systems in psoriasis. 
Clin Dermatol. 2007 Nov-Dec;25(6):616-24. 
8. Arakawa A, Siewert K, Stöhr J, Besgen P, Kim SM, Rühl G, et al. Melanocyte antigen 
triggers autoimmunity in human psoriasis. J Exp Med. 2015 Dec 14;212(13):2203-12. 
9. 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. 
10. Leonardi C, Matheson R, Zachariae C, Cameron G, Li L, Edson-Heredia E, et al. 
Anti­interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl 
J Med. 2012 Mar 29;366(13):1190-9. 
11. Krueger JG, Ferris LK, Menter A, Wagner F, White A, Visvanathan S, et al. Anti-IL-23A 
mAb BI 655066 for treatment of moderate-to-severe psoriasis: safety, efficacy, 
pharmacokinetics, and biomarker results of a single-rising-dose, randomized, 
double­blind, placebo-controlled trial. J Allergy Clin Immunol. 2015 Jul;136(1):116-24. 
12. Papp K, Thaçi D, Reich K, Riedl E, Langley RG, Krueger JG, et al. Tildrakizumab 
(MK­3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a 
phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015 Oct;173(4):930-9. 
1
 
 
 
 


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14. Heydendael VM, Spuls PI, Opmeer BC, de Borgie CA, Reitsma JB, Goldschmidt WF, 
et al. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. 
N Engl J Med. 2003;349(7):658-65. 
15. Patel RV, Clark LN, Lebwohl M, Weinberg JM. Treatments for psoriasis and the risk of 
malignancy. J Am Acad Dermatol. 2009 Jun;60(6):1001-17. 
16. Corominas M, Gastaminza G, Lobera T. Hypersensitivity reactions to biological drugs. 
J Investig Allergol Clin Immunol. 2014;24(4):212-25. 
17. Sahu N, August A. ITK inhibitors in inflammation and immune-mediated disorders. 
Cur Top Med Chem. 2009;9(8):690-703. 
18. Liao XC, Littman DR. Altered T cell receptor signaling and disrupted T cell development 
in mice lacking Itk. Immunity. 1995 Dec;3:757-69. 
19. Mueller C, August A. Attenuation of immunological symptoms of allergic asthma in 
mice lacking the tyrosine kinase ITK. J Immunol. 2003 May 15;170:5056-63. 
 
 
 
 
25. Pfizer. Tanezumab Arthritis Advisory Committee Briefing Document. 2012 Feb 08. 
 
27. Gimbel JS, Kivitz AJ, Bramson C, Nemeth MA, Keller DS, Brown MT, et al. Long-term 
safety and effectiveness of tanezumab as treatment for chronic low back pain. Pain. 2014 
Sep;155(9):1793-801.  


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29. U.S. Department of Health and Human Services. National Institutes of Health. National 
Cancer Institute. Common terminology criteria for adverse events (CTCAE) Version 4.0. 
2009 May 28 (v4.03: 2010 June 14). 

SAP_001.pdf: 
 
ClinicalTrials.gov Posted Document Cover Page 
Clinical Study Statistical Analysis Plan (SAP) 
 
PROTOCOL TITLE:  
A Multicenter, Randomized, Double-blind, PlaCebo-controlled, 
Parallel-group Study to EvaLuate the Safety and Efficacy of 
JTE-051 Administered for 12 Weeks in Subjects with ModeRate 
to Severe Plaque PSoriasis (CLEAR-PS) 
PROTOCOL NUMBER: AE051-G-16-007 
SAP DATE:  
15 January 2019 
NCT NUMBER: 
NCT03358290 
 


JTE-051 
AKROS PHARMA INC. 
Statistical Analysis Plan – Protocol AE051-G-16-007 
 
 
 
Version 1.0 – 15 Jan 2019 
1 
CONFIDENTIAL 
 
 
 
 
 
 
CONFIDENTIAL 
 
 
Akros Pharma Inc. 
 
 
Protocol AE051-G-16-007  
 
A Multicenter, Randomized, Double-blind, PlaCebo-controlled, Parallel-group Study to 
EvaLuate the Safety and Efficacy of JTE-051 Administered for 12 Weeks in Subjects with 
ModeRate to Severe Plaque PSoriasis (CLEAR-PS) 
 
Statistical Analysis Plan 
 
 
 
Version 1.0 
15 January 2019




JTE-051 
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Statistical Analysis Plan – Protocol AE051-G-16-007 
 
 
 
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Table of Contents 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ...............................................................4 
1. 
INTRODUCTION .................................................................................................................................5 
2. 
OBJECTIVES ........................................................................................................................................5 
3. 
STUDY DESIGN ...................................................................................................................................5 
 
STUDY PROCEDURES ............................................................................................................................6 
4. 
SUBJECT POPULATIONS ............................................................................................................... 10 
 
RANDOMIZED POPULATION ................................................................................................................ 10 
 
SAFETY POPULATION ......................................................................................................................... 10 
5. 
STATISTICAL ANALYSIS ............................................................................................................... 10 
 
DISPOSITION ....................................................................................................................................... 10 
 
SAFETY ............................................................................................................................................... 10 
 
EFFICACY ........................................................................................................................................... 11 
6. 
APPENDICES ...................................................................................................................................... 12 
 
LIST OF SUMMARY TABLES ................................................................................................................ 12 
 
LIST OF DATA LISTINGS ..................................................................................................................... 13 
 
TABLE AND LISTING MOCKUPS .......................................................................................................... 14 
 
 
 
 


JTE-051 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition of term 
AE 
Adverse event  
AI-NRS 
Average-itch numeric rating scale 
BMI 
Body mass index 
BSA 
Body surface area  
CRF 
Case report form  
CSR 
Clinical study report 
DB 
Double-blind 
ECG 
Electrocardiogram  
ITT 
Intent-To-Treat  
MedDRA 
Medical Dictionary for Regulatory Activities  
NRS 
Numeric rating scale 
PK 
Pharmacokinetics  
PASI 
Psoriasis Area and Severity Index  
PP 
Per protocol  
QD 
SAE 
Once daily  
Serious adverse event 
SAP 
Statistical analysis plan  
sPGA 
Static Physician’s Global Assessment  
TEAE 
Treatment-emergent adverse event  
WI-NRS 
Worst-itch numeric rating scale 


JTE-051 
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1. INTRODUCTION 
This Statistical Analysis Plan (SAP) describes the statistical methods and data presentations to be 
used in the summary tables and listings of study AE051-G-16-007. No figures are planned due to 
the limited amount of data. 
This document has been prepared based on Protocol Amendment 4, Version 5.2 – 8 Oct 2018 and 
Case Report Form (CRF) Amendment 1, Version 2.0 – 22 May 2018. Details on the study conduct 
and data collection can be found in the protocol and the CRF. 
2. OBJECTIVES 
 To evaluate the efficacy of JTE-051 administered for 12 weeks in subjects with moderate to 
severe plaque psoriasis. 
 To evaluate the safety and tolerability of JTE-051 administered for 12 weeks in subjects with 
moderate to severe plaque psoriasis. 
 To evaluate the pharmacokinetics (PK) of JTE-051 administered for 12 weeks in subjects with 
moderate to severe plaque psoriasis. 
3. STUDY DESIGN 
This is a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study 
in subjects with moderate to severe plaque psoriasis.  
Eligible subjects will be randomized at Visit 2 to receive JTE-051 50 mg, 100 mg, 150 mg, 200 mg 
or placebo once daily (QD) for 12 weeks. Approximately 85 subjects are planned to be randomized 
into 5 treatment groups. A follow-up visit will take place approximately 4 weeks after the last dose 
of study drug. Randomization will be stratified based on prior exposure of subjects to biologic 
therapy (i.e., biologic treatment naïve vs. biologic treatment experienced subjects). 
The study duration will be of approximately 20 weeks per subject:  
• 
Up to a 28-day Screening Period 
• 
A 12-week double-blind Treatment Period 
• 
A 4-week Follow-up Period


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 Study Procedures 
The schedule of study procedures is described in the following Figure 1 and Table 1. 
 
Figure 1. 
Planned Study Schema 
 
 
 
 
 
 
 
 
 
 
 
 
 
JTE-051 50 mg QD (N=17) 
JTE-051 100 mg QD (N=17) 
Placebo QD (N=17) 
Treatment 
12 weeks 
Up to 4 weeks 
V2 
Rand. 
V4 
 
V = Study Visit 
Rand. = Randomization 
FU = Follow-up   
V1 
2 weeks 2 weeks 
4 weeks 
4 weeks 
Screening 
4 weeks 
 
Follow-up 
Approx. 4 weeks 
 
V6 
4 weeks 
V7 
FU 
= Double-blind Treatment Period 
V5 
JTE-051 150 mg QD (N=17) 
JTE-051 200 mg QD (N=17) 
V3 


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Table 1. 
Planned Schedule of Study Procedures 
 
Note: All study procedures should be performed at each study visit prior to study drug administration; 
except for appropriate PK samples collection procedures as discussed below (see Figure 2). When 
scheduled at the same time points, electrocardiogram (ECG) and vital sign parameters collection activities 
should be performed prior to procedures involving venipuncture 
. 
Screening
Period
Follow-up
Period
Duration/ Study Week (Day)a
 Up to 4 
weeks
Week 0
(Day 1)
Week 2
(Day 14±2)
Week 4
(Day 28±2)
Week 8
(Day 56±2)
Week 12
(Day 84±2)
Week 16
(Day 112±2)
Visit
1
2
3
4
5
6
7
Sign Informed Consent
X
Inclusion/ Exclusion Criteria
X
X
Medical History
X
Demographic Information
X
Review Prior/ Concomitant Medications
X
X
X
X
X
X
X
Physical Exam
X
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
X
Body Weight
X
X
X
Height and Calculate BMI 
X
12-Lead ECG
X
X
X
X
Chest Radiographyc
X
TB test (quantiFERON gold OR PPD Test)
X
Drugs of Abuse Screen & alcohol
X
Viral Serology (HBs Ag, HCV Ab, HIV Ab)
X
FSHd
X
HbA1c
X
Pregnancy Test (all females)d
X
X
X
X
X
X
X
Serum Biochemistry
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
Coagulation
X
X
X
X
X
Lipid Profile
X
X
X
X
X
Serum IgG, IgM and IgA 
X
X
25-hydroxyvitamin D
X
Psoriasis Body Surface Area
X
X
X
X
X
X
X
Bone-specific ALP
X
X
X
PASI
X
X
X
X
X
X
X
sPGA
X
X
X
X
X
X
X
Skindex 16
X
X
X
X
X
X
Itch NRS 
Digital Photographyg
X
X
Randomization using IWRS
X
Access IWRS and Dispense Study Drugh
X
X
X
X
Collect Study Drug and Check Compliancej
X
X
X
X
Study Drug Administrationk
X
X
X
X
JTE-051 PK Blood Samplesl
X
X
X
X
X
Document Adverse Eventsm
X
X
X
X
X
X
X
Treatment  Period


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a. 
The target day for each visit after randomization will be calculated relative to the date of Randomization Visit 
(Visit 2) and not relative to the date of the previous visit. All visits should be performed within the windows 
specified in the table. Every attempt should be made to have the subject attend each visit as scheduled. The 
investigational site is encouraged to a make a reminder phone call to the subject approximately a day or two 
before the scheduled visit. However, if a subject is unable to attend a visit within the specified windows, the visit 
should be scheduled as closely as possible to these windows. A subject should not skip a protocol-specified visit 
due to scheduling difficulties. 
c. 
Chest radiography may not be performed if it has been performed within 12 weeks of Visit 1 and documentation 
is available for review by the Investigator and inclusion in the subject’s file. 
d. At Visit 1, serum pregnancy test will be performed for all female subjects. At Visits 2 through 7, urine pregnancy 
tests will be performed only for female subjects of child bearing potential. At Visit 1, females with a documented 
history of lack of menses for ≥12 consecutive months with no other reversible medical etiology will be considered 
postmenopausal. If the female is positive for lack of menses but onset has been ˂12 months, then an FSH >40 
will be required to define post-menopausal status, otherwise subject is considered of childbearing potential. 
e. 
Both worse-itch numeric rating scale (WI-NRS) and average-itch numeric rating scale (AI-NRS) during a 24-hour 
recall period will be recorded by the subject once daily from screening through the last visit. 
g. All subjects will be required to take photographs of the 
 four half-body views (i.e., upper anterior, lower anterior, upper posterior, and lower posterior). 
However, if collecting photographs is raised as the reason for not participating in the study, the subject still can 
be part of the study without collecting photographs. In all the photographs, subject identification will be blinded. 
h. At Visit 2 through Visit 5, randomized subjects will receive sufficient study drug blister cards for the period 
between visits. At Visit 6, study drug will not be dispensed. If a study subject discontinues study drug prematurely, 
the termination should be recorded as soon as possible after the decision has been made. 
. 
j. 
Subjects will be instructed to bring all used and unused blister cards to each study visit for accountability purposes. 
Study drug compliance will be calculated by the site at each visit during the Treatment Period starting at Visit 3, 
based on the number of tablets dispensed to and returned by the subject. 
k. Oral administration for 12 weeks starting on the day of randomization at Visit 2, QD in the morning, regardless 
of meals. On study visit days, subjects should take their scheduled study treatment from their existing study drug 
supply (if available) at the site, under the supervision of the investigator or designee after all study-related 
procedures have been performed (except for Visit 6, when no study drug will be administered, as the last dose 
will be taken the day prior to the visit).  
l. 
See Figure 2 for a detailed description of dosing and PK sampling time points. 
m. AE information will be collected at the specified time points as well as at any time when a site staff member 
becomes aware of an AE after the subject signs the informed consent for the study. However, stable or improving 
pre-existing conditions detected through the screening procedures during the Screening Period (e.g., abnormalities 
in ECG, physical examination, 
, vital signs and laboratory tests) are considered to be 
medical history and should be documented accordingly. 
 
 


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Figure 2. 
Dosing and Pharmacokinetic Sample Collection Time  
 
a. 
The exact date and time of dose at each visit at the site will be collected. 
b. The exact date and time of the last three doses prior to the PK sample collection will be collected. 
c. 
The PK samples at pre-dose point (i.e., samples obtained prior to the morning dosing of the study drug at the site) 
are mandatory in all subjects at all sites. Sample collection date and time will be collected. 
d. The PK samples at trough point (relative to dosing of the study drug at the day prior to the visit) are mandatory 
in all subjects at all sites. Sample collection date and time will be collected. 
e. 
Every effort should be made to collect post-dose PK samples (relative to the morning dosing of the study drug at 
the site) from as many subjects/treatment as possible. Sample collection date and time will be collected.  
f. 
The sampling time between post dose blocks (boxes in Figure 2) should be separated by at least 1 hour.  
 


JTE-051 
AKROS PHARMA INC. 
Statistical Analysis Plan – Protocol AE051-G-16-007 
 
 
 
Version 1.0 – 15 Jan 2019 
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4. SUBJECT POPULATIONS 
The Intent-To-Treat (ITT) population, the Per Protocol (PP) population and the PK population are 
mentioned in the protocol but will not be identified in the final analyses due to the early termination 
of the study and the limited amount of data. 
 Randomized Population 
The randomized population consists of all subjects who are randomized at Visit 2 to one of the 
five treatment groups: JTE-051 50 mg QD, 100 mg QD, 150 mg QD, 200 mg QD and placebo QD. 
 Safety Population 
The safety population consists of the randomized subjects who receive at least one dose of JTE-051 
or placebo after the randomization, including those who did not complete the study. 
5. STATISTICAL ANALYSIS 
The study was terminated early due to the results of another study on the same compound and slow 
enrollment in this study. Therefore, the planned sample size of 85 eligible subjects (17 in each 
treatment group) was not achieved. With only 13 subjects randomized until the early study 
termination, there will not be enough data to analyze the planned efficacy and safety endpoints. 
No inferential tests will be performed. Most of the data will be displayed in listings only. 
Titles and headers of all statistical analysis tables will indicate the corresponding study population; 
the number of subjects for the population and for each treatment will be presented in the tables.  
Percentages will be presented to 1 decimal, e.g., xx.x%.  
Baseline is defined as the last non-missing value prior to the first dose of study drug. Missing data 
will not be imputed in this study.  
Unless otherwise noted, all records collected in the study database, including CRF data and any 
external data transfers (such as clinical laboratory results) will be displayed in listings, regardless 
of whether the subject is randomized or not. 
All analysis will be performed using SAS® Version 9.4. 
 Disposition 
Subject disposition will be summarized and tabulated by treatment group and in total. The number 
and percentage of subjects in the randomized and safety populations will be tabulated. Number of 
discontinued subjects and the reasons for discontinuation during the double-blind (DB) treatment 
period will be tabulated for the randomized population. 
 Safety  
The Medical Dictionary for Regulatory Activities (MedDRA) Version 21.0 will be used to map 
verbatim AEs to preferred terms and their respective primary system organ classes.  


JTE-051 
AKROS PHARMA INC. 
Statistical Analysis Plan – Protocol AE051-G-16-007 
 
 
 
Version 1.0 – 15 Jan 2019 
11 
CONFIDENTIAL 
A treatment-emergent AE (TEAE) is defined as any AE with an onset date on or after the first dose 
of study drug. 
The number and percentage of subjects experiencing TEAEs will be tabulated by treatment in an 
overall summary as well as by preferred term and system organ class for the safety population. 
Listings will be provided for serious adverse events (SAEs) and AEs leading to study discontinuation.  
 Efficacy  
For Psoriasis Area and Severity Index (PASI), Static Physician’s Global Assessment (sPGA) and 
Skindex-16 questionnaire, change from baseline will be derived. In addition, percentage change 
from baseline will be derived for PASI score and psoriasis affected Body Surface Area (BSA). 
Skindex-16 questionnaire is reported in a scale of 0 to 6. Each raw score will be multiplied by 
16.667, thus all responses will be transformed to a linear scale of 100 (i.e., from 0 [no effect] to 
100 [effect experienced all the time]). Scale scores are the average of non-missing items in a given 
scale as follows. If any scale has more than 25% of the responses missing, the scale is missing.  
 Symptom scale score: average of items 1-4 
 Emotions scale score: average of items 5-11 
 Functioning scale score: average of items 12-16 
 Total score: average of 16 item 
 
 


JTE-051 
AKROS PHARMA INC. 
Statistical Analysis Plan – Protocol AE051-G-16-007 
 
 
 
Version 1.0 – 15 Jan 2019 
12 
CONFIDENTIAL 
6. APPENDICES 
 List of Summary Tables 
Number 
Title 
14.1.1 
Subject Disposition, Randomized Population 
14.3.1.1 
Overall Summary of Treatment-emergent Adverse Events (TEAEs), Safety 
Population 
14.3.1.2 
Number (%) of Subjects with TEAEs by System Organ Class and Preferred 
Term, Safety Population 
14.3.2.1 
Listing of Serious Adverse Events, Safety Population 
14.3.2.2 
Listing of Adverse Events Leading to Study Discontinuation, Safety Population 
14.3.3 
Clinical Laboratory Normal Ranges in Reported SI Units and Conventional 
Units 
 
 
 


JTE-051 
AKROS PHARMA INC. 
Statistical Analysis Plan – Protocol AE051-G-16-007 
 
 
 
Version 1.0 – 15 Jan 2019 
13 
CONFIDENTIAL 
 List of Data Listings 
Number 
Title  
16.1.7 
Randomization 
16.2.1.1 
Subject Disposition   
16.2.1.2 
Screen Failure Reasons 
16.2.2 
Subject Eligibility   
16.2.4.1 
Demographics 
16.2.4.2 
Plaque Psoriasis History 
16.2.4.3 
Medical History 
16.2.4.4 
Reproductive Status 
16.2.4.5 
Drugs of Abuse/Alcohol Screen 
16.2.4.6 
Serum Pregnancy Test and FSH (Females only) 
16.2.4.7 
Viral Serology at Screening 
16.2.4.8 
Prior Anti-psoriasis Medications 
16.2.4.9 
Prior and Concomitant Medications 
16.2.4.10 
Prior and Concomitant Procedures 
16.2.5.1 
Study Medication Dispensation 
16.2.5.2 
Study Medication Administration 
16.2.5.3 
JTE-051 Plasma Concentration 
16.2.6.1 
Psoriasis Area and Severity Index (PASI) and Psoriasis Affected Body Surface 
Area (BSA) 
16.2.6.2 
Static Physician's Global Assessment (sPGA) 
16.2.6.3 
Skindex-16, Section 1 of 2 
16.2.6.4 
Skindex-16, Section 2 of 2 
16.2.6.5 
Itch Numeric Rating Scale 
16.2.6.7 
Digital Photography Collection 
16.2.7 
Adverse Events  
16.2.8.1.1 
Clinical Laboratory Test Results – Hematology:  
Erythrocytes and Platelets   
16.2.8.1.2 
Clinical Laboratory Test Results – Hematology:  
Leukocytes, Section 1 of 2 
16.2.8.1.3 
Clinical Laboratory Test Results – Hematology:  
Leukocytes, Section 2 of 2 
16.2.8.2.1 
Clinical Laboratory Test Results – Serum Biochemistry:  
Liver Function 
16.2.8.2.2 
Clinical Laboratory Test Results – Serum Biochemistry:  
Electrolytes/Blood Gases/Glucose 
16.2.8.2.3 
Clinical Laboratory Test Results – Serum Biochemistry: 
Lipids/Protein/Inflammation 
16.2.8.2.4 
Clinical Laboratory Test Results – Serum Biochemistry:  
Renal Function/Urate/Creatine Kinase 
16.2.8.2.5 
Clinical Laboratory Test Results – Serum Biochemistry:  


JTE-051 
AKROS PHARMA INC. 
Statistical Analysis Plan – Protocol AE051-G-16-007 
 
 
 
Version 1.0 – 15 Jan 2019 
14 
CONFIDENTIAL 
Number 
Title  
Clinical Laboratory Test Results – Serum Biochemistry: Bone-Specific Alkaline 
Phosphatase, C Reactive Protein, 25-Hydroxyvitamin D and Hemoglobin A1c 
16.2.8.3 
Clinical Laboratory Test Results – Serum Immunoglobulins 
16.2.8.4 
Clinical Laboratory Test Results – Coagulation 
16.2.8.5.1 
Clinical Laboratory Test Results – Urinalysis: Macroscopic 
16.2.8.5.2 
Clinical Laboratory Test Results – Urinalysis: Macroscopic and Microscopic  
16.2.8.5.3 
Clinical Laboratory Test Results – Urinalysis: Microscopic 
16.2.8.5.4 
Clinical Laboratory Test Results – Urinalysis: Crystals 
16.2.8.5.5 
Clinical Laboratory Test Results – Urinalysis: Casts 
16.2.8.6 
Clinical Laboratory Test Comments 
16.2.8.7 
Vital Signs and Body Weight 
16.2.8.8 
12-Lead ECG 
 
 
 Table and Listing Mockups