Clinical trial NCT04999839
Conditions: Moderate to Severe Plaque Psoriasis
Sponsor: Takeda
Start date: 2021-08-11; Completion date: 2022-09-12
Enrollment: 259 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 2b, randomized, multicenter, double-blind, placebo-controlled, multiple-dose study designed to evaluate the efficacy, safety, and tolerability of NDI-034858 in participants with moderate to severe plaque psoriasis. This study will also evaluate the plasma concentrations of NDI-034858 and explore the immune response to NDI-034858 in participants with moderate to severe plaque psoriasis.

Detailed description:
Approximately 259 male and female participants, aged 18 to 70 years (inclusive) were enrolled in this study. Participants were randomized to receive either one of the four doses of NDI-034858, or placebo on Day 1. The goal was to have approximately 50 participants randomized per treatment group (1:1:1:1:1 ratio) on Day 1. During the treatment period, NDI-034858 or placebo was orally administered QD for 12 weeks. The 12 week treatment period was followed by a 4-week safety follow-up period.

Arms: arm 1: Participants received placebo matched to NDI-034858 oral capsules, once daily (QD) for up to 12 weeks. arm 2: Participants received 2 mg of NDI-034858 oral capsules, QD for up to 12 weeks. arm 3: Participants received 5 mg of NDI-034858 oral capsules, QD for up to 12 weeks. arm 4: Participants received 15 mg of NDI-034858 oral capsules, QD for up to 12 weeks. arm 5: Participants received 30 mg (2\*15 mg) of NDI-034858 oral capsules, QD for up to 12 weeks.
Interventions: intervention 1: NDI-034858 study drug intervention 2: NDI-034858 study drug intervention 3: NDI-034858 study drug intervention 4: NDI-034858 study drug intervention 5: Placebo
Intervention descriptions: intervention 1: NDI-034858 2 mg oral capsules. intervention 2: NDI-034858 5 mg oral capsules. intervention 3: NDI-034858 15 mg oral capsules. intervention 4: NDI-034858 30 mg (2\*15 mg) oral capsules. intervention 5: Placebo matched to NDI-034858 oral capsules.

Protocol documents:
Prot_002.pdf: 
NCT Number: NCT04999839
Title: A Phase 2b, Randomized, Multicenter, Double-blind, Placebo-controlled, 
Multiple-dose Study to Evaluate the Efficacy, Safety, and Tolerability of 
NDI-034858 in Subjects With Moderate to Severe Plaque Psoriasis
Study Number: 4858-201 (TAK-279)
Document Version and Date: Version 3.0 (04-February-2022)
Certain information within this document has been redacted (i.e., specific content is 
masked irreversibly from view) to protect either personally identifiable information or 
company confidential information. 
Clinical Study Protocol


Protocol Number 4858-201 
Protocol Version 3.0: 04 Feb-2022 
Confidential 
1 of 94 
A PHASE 2B, RANDOMIZED, MULTICENTER, DOUBLE-BLIND, 
PLACEBO-CONTROLLED, MULTIPLE -DOSE STUDY TO EVALUATE 
THE EFFICACY, SAFETY, AND TOLERABILITY OF NDI-034858 IN 
SUBJECTS WITH MODERATE TO SEVERE PLAQUE PSORIASIS 
PROTOCOL 4858-201 
FINAL 
AMENDMENT 2 
VERSION 3.0 
04-Feb-2022
Sponsor: 
Nimbus Lakshmi, Inc. 
130 Prospect Street, Suite 301 
Cambridge, Massachusetts, United States, 02139 
Telephone: 857-999-2009 
Sponsor Medical 
Expert: 
, MD 
Medical Monitor 
Nimbus Lakshmi, Inc. 
Telephone: 917 601 0024 
Clinical Research 
Organization: 
Innovaderm Research Inc. 
3530 Saint-Laurent Boulevard, Suite 300 
Montreal, Quebec, Canada, H2X 2V1 
Telephone: 514-521-4285 
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TABLE OF CONTENTS 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF TABLES ...........................................................................................................................6 
LIST OF FIGURES .........................................................................................................................6 
PROTOCOL VERSION HISTORY ................................................................................................7 
STATEMENT OF COMPLIANCE ...............................................................................................11 
SIGNATURE PAGE .....................................................................................................................12 
PRINCIPAL/QUALIFIED INVESTIGATOR SIGNATURE PAGE ...........................................13 
LIST OF ABBREVIATIONS ........................................................................................................14 
1. 
PROTOCOL SUMMARY ..........................................................................................19 
1.1. 
Synopsis ......................................................................................................................19 
1.2. 
Study Diagram ............................................................................................................30 
1.3. 
Schedule of Events .....................................................................................................30 
2. 
INTRODUCTION ......................................................................................................35 
2.1. 
Background .................................................................................................................35 
2.1.1. 
Plaque Psoriasis ..........................................................................................................35 
2.1.2. 
NDI-034858 ................................................................................................................35 
2.1.3. 
Study Rationale ...........................................................................................................36 
2.1.4. 
Clinical Experience .....................................................................................................36 
2.2. 
Risk/Benefit Assessment ............................................................................................40 
2.2.1. 
Known Potential Risks ...............................................................................................40 
2.2.2. 
Known Potential Benefits ...........................................................................................42 
2.2.3. 
Assessment of Risks and Benefits ..............................................................................42 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................44 
4. 
STUDY DESIGN .......................................................................................................46 
4.1. 
Overall Design ............................................................................................................46 
4.2. 
Study Conduct During the Coronavirus Disease 2019 Pandemic ..............................47 
4.3. 
Scientific Rationale for Study Design ........................................................................48 
4.4. 
Justification for Dose ..................................................................................................49 
4.5. 
End of Study Definition ..............................................................................................50 
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5. 
STUDY POPULATION .............................................................................................51 
5.1. 
Inclusion Criteria ........................................................................................................51 
5.2. 
Exclusion Criteria .......................................................................................................52 
5.3. 
Screen Failures ............................................................................................................56 
6. 
TREATMENT ............................................................................................................57 
6.1. 
Study Treatment Administered ...................................................................................57 
6.2. 
Preparation/Handling/Storage/Accountability ............................................................58 
6.2.1. 
Preparation/Storage/Handling.....................................................................................58 
6.2.2. 
Accountability .............................................................................................................58 
6.3. 
Randomization ............................................................................................................58 
6.3.1. 
Blinding ......................................................................................................................59 
6.3.2. 
Study Treatment Compliance .....................................................................................59 
6.4. 
Concomitant Therapy .................................................................................................60 
6.4.1. 
Permitted Therapies ....................................................................................................60 
6.4.2. 
Prohibited Therapies or Procedures ............................................................................60 
7. 
DISCONTINUATION AND LOST TO FOLLOW-UP ............................................63 
7.1. 
Discontinuation from Study Treatment ......................................................................63 
7.2. 
Discontinuation from Study ........................................................................................64 
7.3. 
Lost to Follow-Up.......................................................................................................65 
7.4. 
Study Termination ......................................................................................................66 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................67 
8.1. 
Efficacy Assessments .................................................................................................67 
8.1.1. 
Psoriasis Area and Severity Index ..............................................................................67 
8.1.2. 
Physician’s Global Assessment ..................................................................................67 
8.1.3. 
 ......................................................................................................67 
8.1.4. 
 ...................................................................................68 
8.1.5. 
 .........................................................................................68 
8.2. 
Quality-of-Life Assessments/Subject Reported Outcomes ........................................68 
8.2.1. 
Dermatology Life Quality Index Questionnaire .........................................................68 
8.3. 
Safety and Other Assessments ....................................................................................68 
8.3.1. 
Vital Signs ..................................................................................................................68 
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8.3.2. 
Physical Examination .................................................................................................68 
8.3.3. 
Targeted Physical Examination ..................................................................................69 
8.3.4. 
Clinical Laboratory Tests ...........................................................................................69 
8.3.5. 
Electrocardiogram .......................................................................................................71 
8.3.6. 
Plasma Concentration of NDI-034858 .......................................................................71 
8.3.7. 
................................................................................72 
8.3.8. 
 ...............................................................................72 
8.3.9. 
...................................................................72 
8.3.10. 
 ..............................................................72 
8.3.11. 
Medical Photography ..................................................................................................73 
8.4. 
Adverse Events and Serious Adverse Events .............................................................73 
8.4.1. 
Definition of Adverse Event .......................................................................................73 
8.4.2. 
Definition of Serious Adverse Event ..........................................................................73 
8.4.3. 
Classification of an Adverse Event .............................................................................74 
8.4.4. 
Time Period and Frequency for Event Assessment and Follow-Up ...........................75 
8.4.5. 
Adverse Event Reporting ............................................................................................76 
8.4.6. 
Serious Adverse Event Reporting ...............................................................................76 
8.4.7. 
Adverse Events of Special Interest .............................................................................76 
8.4.8. 
Potential Drug Induced Liver Injury ...........................................................................78 
8.4.9. 
Pregnancy Reporting ..................................................................................................79 
8.4.10. 
Overdose .....................................................................................................................79 
9. 
STATISTICAL CONSIDERATIONS .......................................................................80 
9.1. 
Sample Size Determination ........................................................................................80 
9.2. 
Populations for Analyses ............................................................................................80 
9.3. 
Statistical Analyses .....................................................................................................80 
9.3.1. 
General Approach .......................................................................................................80 
9.3.2. 
Efficacy Analyses .......................................................................................................81 
9.3.3. 
Safety Analyses ..........................................................................................................81 
9.3.4. 
Pharmacokinetic Analyses ..........................................................................................82 
9.3.5. 
 .......................................................................................82 
9.3.6. 
Other Analyses ............................................................................................................82 
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9.3.7. 
Planned Interim Analyses ...........................................................................................82 
10. 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS ..................................................................................................83 
10.1. 
Local Regulations/Declaration of Helsinki ................................................................83 
10.2. 
Ethical Review ............................................................................................................83 
10.3. 
Informed Consent Process ..........................................................................................83 
10.4. 
Study Discontinuation and Closure ............................................................................84 
10.5. 
Confidentiality and Privacy ........................................................................................84 
10.6. 
Clinical Monitoring ....................................................................................................85 
10.7. 
Quality Assurance and Quality Control ......................................................................85 
10.8. 
Data Handling and Record Keeping ...........................................................................85 
10.9. 
Protocol Deviations ....................................................................................................86 
10.10. 
Publication Policy .......................................................................................................86 
11. 
REFERENCES ...........................................................................................................87 
APPENDIX 1. PARTIAL LIST OF STRONG OR MODERATE INHIBITORS OF 
CYP3A4 ......................................................................................................................89 
APPENDIX 2. PSORIASIS AREA AND SEVERITY INDEX .................................................90 
APPENDIX 3. 
........................................................91 
APPENDIX 4. 
..................................................................92 
APPENDIX 5. DERMATOLOGY LIFE QUALITY INDEX ....................................................93 
 
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LIST OF TABLES 
Table 1:      Schedule of Events .....................................................................................................32 
Table 2: 
Potential Risks of NDI-034858 ..................................................................................40 
Table 3: 
Study Treatments ........................................................................................................57 
Table 4: 
Prohibited Therapies or Procedures ............................................................................61 
Table 5: 
Physician’s Global Assessment ..................................................................................67 
Table 6: 
Clinical Laboratory Testing ........................................................................................70 
LIST OF FIGURES 
Figure 1: 
Study Diagram ............................................................................................................30 
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PROTOCOL VERSION HISTORY 
Version 
Reason for amendment 
Main changes to the protocol 
1.0 / 21-May-2021 
Initial version 
N/A 
2.0-Amendment 1/ 
02-Sep-2021 
To add clarity and implement 
minor corrections to text 
Global: Minor administrative changes to 
the protocol for clarity and to correct 
typographical or minor errors were 
implemented. 
 
To update the list of secondary 
 efficacy 
endpoints for clarity of intended 
analysis 
Section 1.1 and Section 3: The list of 
secondary 
 efficacy endpoints was 
updated. 
 
To clarify or add the 
photographic process for 
biopsies or the photographic 
process for medical photographs 
of full body. 
Section 1.1; Section 1.3, Table 1; 
Section 4.1; Section 8.3.11; Section 
8.3.11.1 (added section; and Section 
8.3.11.2 (added section): Optional 
medical photographs were added to 
Week 4 visit. It was also clarified that 
for all subjects consenting to biopsy 
collection, the biopsied areas will be 
photographed and for a subset of 
subjects who consent to the procedure, 
photographs of the full body (front and 
back) will be performed.  
 
To clarify the list of highly 
effective methods of 
contraception. 
Section 1.1 and Section 5.1, Inclusion 
Criterion 7: It was clarified that bilateral 
tubal ligation or occlusion are both 
considered as highly effective methods 
of contraception. 
 
To clarify which systemic 
corticosteroid treatments are 
exclusionary, prohibited, and/or 
trigger discontinuation of study 
treatment. 
Section 1.1 and Section 5.2, Exclusion 
Criterion 21; Section 6.4.2, Table 4; and 
Section 7.1: It was clarified that oral, 
intravenous, intramuscular, and 
intralesional injections of corticosteroids 
are prohibited during the study. In 
addition, use of oral, intravenous, or 
intramuscular steroids will lead to 
subject permanent discontinuation from 
study treatment. 
 
To clarify that non-
live -attenuated vaccines for 
COVID-19 are allowed during 
the study. 
Section 1.1 and Section 5.2, Exclusion 
Criterion 24; Section 6.4.2, Table 4; and 
Section 7.1: It was clarified that non-
live -attenuated vaccines for COVID-19 
are allowed during the study. 
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Version 
Reason for amendment 
Main changes to the protocol 
 
To exclude subjects enrolled in 
previous studies of NDI-034858 
to minimize bias. 
Section 1.1 and Section 5.2, Exclusion 
Criterion 27: exclusion criteria added. 
 
To update or add unscheduled 
visits, virtual visits, direct-to-
subject shipping of study 
product, and local lab use 
processes as appropriate, 
including for COVID-19 
mitigation. 
Section 1.3; Section 4.2; Section 8.3.4.1 
(added section): Unscheduled visits, 
virtual visits, direct-to-subject shipping 
of study product processes, as well as 
process for use of local laboratories were 
added. 
 
To update the criteria for 
mandatory, permanent 
discontinuation from study 
treatment from cytopenia of 
Grade ≥2 to cytopenia of 
Grade ≥3. 
Section 2.2.1, Table 2; Section 7.1; 
Section 8.3.4; and Section 8.4.7: The 
reason for permanent discontinuation 
from study treatment due to cytopenia 
was updated from cytopenia of Grade ≥2 
to cytopenia of Grade ≥3. 
 
To include a definition of 
noncompliance pertaining to 
missed doses. 
Section 6.3.2: The number of doses 
missed to clearly state the definition of 
noncompliance pertaining to missed 
doses was added.  
 
To clarify the process to follow 
if a subject starts prohibited 
medication or procedure. 
Section 6.4.2: The process to follow if a 
subject starts prohibited medication or 
procedure was clarified. 
 
To clarify the potential reasons 
for permanent discontinuation 
from study treatment. 
Section 7.1: Potential reasons for subject 
permanent discontinuation from study 
treatment were updated. 
 
To clarify that subjects who 
discontinue before Day 1 dosing 
could be replaced. 
Section 7.2: It was clarified that subjects 
who discontinue after Day 1 dosing will 
not be replaced. 
 
To clarify the potential reasons 
for discontinuation from study. 
Section 7.2: Potential reasons for subject 
permanent discontinuation from study 
were updated 
 
To clarify that an indeterminate 
QuantiFERON-TB test result 
obtained at screening can be 
repeated once.  
Section 8.3.4: It was clarified that a 
QuantiFERON-TB test can only be 
repeated once if the result is 
indeterminate; tests with positive or 
negative results will not be repeated. 
 
To update the process for 
reporting of serious adverse 
events (SAEs), adverse events of 
Section 8.4.6; Section 8.4.7.1 (added 
section); and Section 8.4.9: The 
reporting process for SAEs. AESIs, and 
pregnancies was updated. 
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Version 
Reason for amendment 
Main changes to the protocol 
special interest (AESIs), and 
pregnancies. 
 
To incorporate into AESI an 
extended list of events 
characteristic of inhibitors 
targeting other JAK family 
kinases. 
Section 8.4.7: Additional AESIs were 
included according to the known adverse 
effects of JAK inhibitors, including 
major cardiovascular events, 
thromboembolic events, gastrointestinal 
perforation, malignancies, infections, 
and AEs of abnormal liver function tests, 
and renal dysfunction. 
 
To clarify the sample size 
determination. 
Section 9.1: The sample size was 
calculated using two different methods 
in the original protocol, only the 
appropriate method was kept in this 
section. 
3.0-Amendment 2/ 
04-Feb-2022 
To add clarity and implement 
minor corrections to text 
Global: Minor administrative changes to 
the protocol for clarity and to correct 
typographical or minor errors were 
implemented 
 
To further clarify Inclusion 
Criterion 7 
Section 1.1 and Section 5.1 were 
updated. 
 
To correct a typo in Inclusion 
Criterion 9 
Section 1.1 and Section 5.1 were 
updated. 
 
To clarify the Schedule of 
Events 
Section 1.3, Table 1: Week 16 column 
edited to clarify assessments and 
procedures done only at early 
termination visits that occur before Week 
12.  
 
To clarify process/timing of 
eligibility assessment prior to 
randomization 
Section 1.3, Table 1: Footnote a was 
modified to reflect the clarification. 
Section 6.3 was updated accordingly. 
 
To update the criteria for 
temporary or permanent 
discontinuation of study drug in 
case of cytopenia CTCAE Grade 
≥2. 
Section 2.2.1, Table 2; Section 7.1; 
Section 8.3.4; and Section 8.4.7 were 
updated. 
 
To clarify reporting of adverse 
events and clinically significant 
laboratory abnormalities 
Section 1.3, Table 1, Footnote r; 
Section 8.3.1; Section 8.3.2; 
Section 8.3.3, Section 8.3.4; 
Section 8.4.4; Section 8.4.6; 
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Version 
Reason for amendment 
Main changes to the protocol 
Section 8.4.7 and Section 8.4.9 were 
updated. 
To update the BMI range 
indicated in the inclusion criteria 
Section 1.1 and Section 5.1: Inclusion 
criterion 10 was updated. 
To update the laboratory tests 
allowed for TB screening 
Section 1.1; Section 1.3, Foootnote c; 
Section 5.2, Exclusion Criterion 17; 
Section 8.3.4, and Section 8.3.4.1  were 
updated. 
To clarify that intraarticular and 
intrathecal corticosteroid 
injections are prohibited 
Section 1.1; Section 5.1, Exclusion 
Criterion 21; Section 6.4.2 (Table 4), and 
Section 7.1 were updated. 
To clarify that non-live-
attenuated boosters for COVID-
19 are allowed 
Section 1.1; Section 5.2, Exclusion 
Criterion 24; Section 6.4.2, Table 4; and 
Section 7.1 were updated. 
To clarify statistical analyses 
and align with the statistical 
analysis plan.  
Section 1.1;Section 9.2 and Section 9.3.1 
were updated.  
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STATEMENT OF COMPLIANCE 
The study will be conducted in accordance with the protocol, International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP), and applicable local regulations. The 
principal investigator will assure that no planned deviation from, or changes to the protocol will 
take place without prior agreement from the sponsor and documented approval from the 
institutional review board (IRB)/research ethics board (REB), except where necessary to 
eliminate an immediate hazard(s) to the study subjects. All personnel involved in the conduct of 
this study have completed ICH GCP training. 
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IRB/REB for review and approval. Approval of both the protocol and the 
consent form must be obtained before any subject is enrolled. Any amendment to the protocol 
will require review and approval by the IRB/REB before the changes are implemented to the 
study. All changes to the consent form will be IRB/REB approved. 
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SIGNATURE PAGE
The signatures below constitute the approval of this protocol and provide the necessary 
assurances that this study will be conducted according to this protocol, applicable local 
regulations, and ICH GCP guidelines. 
Name
Title
Signature and date
(DD-MMM-YYYY)
, MD 
, Early
Clinical Development
Nimbus Lakshmi, Inc. 
 
 
 
 
 
 
, BSc
, Scientific and 
Regulatory Affairs 
Innovaderm Research Inc. 
 
 
 
 
 
 
, MSc 
, Biometrics
Innovaderm Research Inc. 
 
 
 
 
 
 
07-Feb-2022
,7190436Ā-6:25782Ā/,(Ā$!'$,!'&Ȁ. ",Ȁ$""'Ȁ&."#Ȁ%# #!*%. )+"
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PRINCIPAL/QUALIFIED INVESTIGATOR SIGNATURE PAGE 
 
Investigator Name: 
 
 
 
 
Signature: 
 
Date: 
 
 
` 
` 
(DD-MMM-YYYY) 
Institution Name:  
 
 
By my signature, I agree to personally supervise the conduct of this study at my study site and 
to ensure its conduct in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki and in compliance with the protocol, informed consent, institutional 
review board/independent ethics committee procedures, instructions from sponsor’s 
representatives, ICH GCP guidelines, and applicable local regulations governing the conduct 
of clinical studies. 
 
 
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LIST OF ABBREVIATIONS 
Abbreviation or Specialist Term 
Explanation 
AE 
adverse event 
ADL 
activities of daily living 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
anti-HBc 
antibody to hepatitis B core antigen 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
area under the concentration versus time curve 
AUC% 
percentage of the area under the concentration versus time curve 
AUC0-inf 
area under the plasma concentration versus time curve from time 
0 to infinity 
AUC0-last 
area under the plasma concentration versus time curve from time 
0 to the time of last measurable concentration 
AUC0-tau 
area under the plasma concentration versus time curve from time 
0 to the end of the dosing period 
β-hCG 
β-human chorionic gonadotropin 
BMI 
body mass index 
BSA 
body surface area 
BUN 
blood urea nitrogen 
Cavg 
average concentration over the dosing interval 
CLr 
renal clearance 
Cmax 
maximum observed concentration 
Cmin 
minimum observed concentration 
CMH 
Cochran-Mantel-Haenszel 
COVID-19 
Coronavirus Disease 2019 
CPK 
creatine phosphokinase 
CRO 
contract research organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough 
trough concentration 
CV 
coefficient of variation 
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Abbreviation or Specialist Term 
Explanation 
CYP3A 
cytochrome P450 3A 
DDI 
drug drug interaction 
DILI 
drug induced liver injury 
DLQI 
Dermatology Life Quality Index 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOS 
end of study 
EOT 
end of treatment 
ET 
early termination 
F% 
oral bioavailability 
FDA 
Food and Drug Administration 
FE% 
fraction of the dose excreted in urine 
FIH 
first in human 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl-transferase 
hADME 
human absorption, distribution, metabolism, and excretion 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCT 
hematocrit 
HCV 
hepatitis C virus 
Hgb 
hemoglobin 
HIV 
human immunodeficiency virus 
IB 
Investigator Brochure 
IC30 
30% inhibitory concentration 
IC50 
half maximal inhibitory concentration 
IC50 
90% inhibitory concentration 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
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Abbreviation or Specialist Term 
Explanation 
IL 
interleukin 
IND 
Investigational New Drug 
IFNγ 
interferon gamma 
INR 
international normalized ratio 
IRB 
institutional review board 
ITT 
intent-to-treat  
IV 
intravenous 
IWRS 
Interactive Web Response System 
JAK 
Janus kinase 
LOCF 
last observation carried forward 
LMW 
low molecular weight  
MAD 
multiple ascending dose 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MedDRA  
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat 
MMRM 
mixed effect model repeated measures method 
MPV 
mean platelet volume 
 
 
N/A 
not applicable 
NCI 
National Cancer Institute 
NMSC 
nonmelanoma skin cancer 
NOAEL 
no observable adverse effect level 
 
 
PASI 
Psoriasis Area and Severity Index 
PASI-100 
100% improvement from baseline in Psoriasis Area and Severity 
Index 
PASI-50 
50% improvement from baseline in Psoriasis Area and Severity 
Index 
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Abbreviation or Specialist Term 
Explanation 
PASI-75 
75% improvement from baseline in Psoriasis Area and Severity 
Index 
PASI-90 
90% improvement from baseline in Psoriasis Area and Severity 
Index 
PBPK 
physiologically based pharmacokinetic 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic 
PDE4 
phosphodiesterase Type 4 
PGA 
Physician’s Global Assessment 
PK 
pharmacokinetic  
PLT 
platelets 
PP 
per-protocol  
PT 
prothrombin time 
PUVA 
Psoralen and ultraviolet A 
QC 
quality control 
QD 
once daily 
RBC 
red blood cell (count) 
REB 
research ethics board 
SAD 
single ascending dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SDD 
spray dried dispersion 
SOC 
system organ class 
sPGA 
static Physician’s Global Assessment 
STAT 
signal transducers and activators of transcription 
t1/2 
terminal half-life 
TB 
tuberculosis  
TBT 
T-Spot.TB test 
TEAE 
treatment-emergent adverse event 
Th 
T helper 
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Abbreviation or Specialist Term 
Explanation 
Tmax 
time to maximum observed concentration 
TNF 
tumor necrosis factor 
TPGS 
d-α-tocopheryl polyethylene glycol 1000 succinate 
TYK2 
tyrosine kinase 2 
UV 
ultraviolet 
WBC 
white blood cell (count) 
WHO-DD 
World Health Organization - Drug Dictionary 
WOCBP 
women of childbearing potential 
 
 
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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Name of Sponsor/Company: 
Nimbus Lakshmi, Inc. 
Name of Investigational Product: 
NDI-034858 
Name of Active Ingredient: 
NDI-034858 
Title of Study:  
A Phase 2b, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Multiple -Dose Study to 
Evaluate the Efficacy, Safety, and Tolerability of NDI-034858 in Subjects with Moderate to Severe 
Plaque Psoriasis 
Phase of Development:  
Phase 2b 
Study Sites:  
Approximately 60 study sites located in Canada and the United States will participate in this study. 
Number of Subjects (planned):  
Approximately 250 subjects will be randomized in this study (approximately 50 subjects/arm). 
Duration of Study:  
The maximum study duration per subject is approximately 20 weeks, including up to 30 days for the 
screening period, a 12-week treatment period, and a 4-week safety follow-up period. 
Investigational Products, Dosage, and Mode of Administration:  
NDI-034858 at doses of 2 mg, 5 mg, 15 mg, or 30 mg, or placebo will be orally administered once 
daily (QD) for 12 weeks. NDI-034858 will be available in 2 mg, 5 mg, and 15 mg strength capsules. 
Matching placebo will be identical to NDI-034858 but will not contain the active ingredient.  
Subjects will be randomized in a 1:1:1:1:1 ratio. 
Objectives: 
The primary objective is: 
• 
To assess the efficacy of NDI-034858 orally administered QD at 2 mg, 5 mg, 15 mg, or 
30 mg for 12 weeks in subjects with moderate to severe plaque psoriasis 
The secondary objectives are: 
• 
To assess the safety and tolerability of NDI-034858 orally administered QD at 2 mg, 5 mg, 
15 mg, or 30 mg for 12 weeks in subjects with moderate to severe plaque psoriasis 
• 
To evaluate the plasma concentration of NDI-034858 orally administered QD at 2 mg, 
5 mg, 15 mg, or 30 mg in subjects with moderate to severe plaque psoriasis 
The exploratory objectives are: 
 
 
 
 
 
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Name of Sponsor/Company: 
Nimbus Lakshmi, Inc. 
Name of Investigational Product: 
NDI-034858 
Name of Active Ingredient: 
NDI-034858 
 
 
 
Endpoints: 
Primary efficacy endpoint: 
• 
Proportion of subjects achieving at least a 75% improvement from baseline in Psoriasis 
Area and Severity Index (PASI-75) at Week 12 
Secondary efficacy endpoints: 
• 
Proportion of subjects achieving a Physician Global Assessment (PGA) of clear (0) or 
almost clear (1) at Week 12 
• 
Proportion of subjects achieving at least a 90% improvement from baseline in Psoriasis 
Area and Severity Index (PASI-90) at Week 12 
• 
Proportion of subjects achieving a 100% improvement from baseline in Psoriasis Area and 
Severity Index (PASI-100) at Week 12 
• 
Change from baseline in Dermatology Life Quality Index (DLQI) at Week 12 
Exploratory 
 endpoints: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Secondary safety endpoints: 
• 
Incidence of adverse events (AEs) 
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Name of Sponsor/Company: 
Nimbus Lakshmi, Inc. 
Name of Investigational Product: 
NDI-034858 
Name of Active Ingredient: 
NDI-034858 
• 
Changes in vital signs, clinical laboratory parameters, and electrocardiograms (ECGs) 
Secondary pharmacokinetic (PK) endpoint: 
• 
Measurement of plasma concentrations of NDI-034858 in subjects receiving active 
treatment 
Exploratory 
 endpoints: 
 
 
 
 
Study Design 
This is a Phase 2b, randomized, multicenter, double-blind, placebo-controlled, multiple dose study 
designed to evaluate the efficacy, safety, and tolerability of NDI-034858 in subjects with moderate to 
severe plaque psoriasis. This study will also evaluate the plasma concentrations of NDI-034858 and 
explore the immune response (in blood and skin) to NDI034858 in subjects with moderate to severe 
plaque psoriasis.  
Approximately 250 male and female subjects, aged 18 to 70 years (inclusive), with moderate to severe 
plaque psoriasis will be randomized in this study. To be eligible for the study, the subjects will need to 
have a history of plaque psoriasis for at least 6 months prior to the screening visit. In addition, the 
subjects will need to have the following characteristics at screening and on Day 1: PASI score ≥ 12, 
PGA score ≥ 3, and BSA involved with plaque psoriasis ≥ 10%. 
All subjects will read and sign an informed consent form (ICF) prior to any screening procedures being 
performed. Subjects who fulfill all inclusion criteria and none of the exclusion criteria will be included 
into the study. During a screening period of no longer than Day -30 to Day -1, subjects will be 
randomized (on Day -7) to receive either one of the four doses of NDI-034858 (2 mg, 5 mg, 15 mg, or 
30 mg), or placebo on Day 1. The goal is to have approximately 50 subjects randomized per treatment 
group (1:1:1:1:1 ratio) on Day 1. During the treatment period, NDI-034858 (2 mg, 5 mg, 15 mg, or 
30 mg) or placebo will be orally administered QD for 12 weeks. The 12-week treatment period will be 
followed by a 4-week safety follow-up period.  
For scheduled study visits, subjects will come to the study site on 8 occasions: screening, Day 1, and 
Weeks 1, 2, 4, 8, 12 (end of treatment [EOT]), and 16 (end of study [EOS] / early termination visit 
[ET]).  
Efficacy will be assessed using PASI, PGA, 
 
. Quality of life will be evaluated using 
DLQI.  
Safety will be assessed by collecting AEs, recording vital signs, performing physical examinations, and 
evaluating clinical laboratory and ECGs results.  
Blood samples will be collected to measure plasma levels of NDI-034858 as follows: 
• 
On Day 1 prior to dosing and 1 hour (± 5 min) post-dosing; 
• 
At Week 4 prior to dosing, 1 hour (± 5 min) postdosing, and 4 hours (± 10 min) post-
dosing; 
• 
At Week 8 prior to dosing; 
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Protocol Version 3.0: 04-Feb-2022 
 
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Name of Sponsor/Company: 
Nimbus Lakshmi, Inc. 
Name of Investigational Product: 
NDI-034858 
Name of Active Ingredient: 
NDI-034858 
• 
At Week 12 anytime (no study treatment administration at this visit).  
• 
At ET visit anytime (if ET visit is planned before Week 12 visit). 
Urine samples will be collected on Day 1, and at Weeks 4, 12, and 16 
 
  
 
 
 
 
 
 
 
 
. 
Inclusion/Exclusion Criteria: 
Inclusion criteria:  
In order to be eligible to participate in this study, a subject must meet all following criteria, either at the 
screening and Day 1 visits or only at one of the specified visits (screening or Day 1) as noted in the 
criterion: 
1. Male or female subject aged 18 to 70 years, inclusive, at the time of consent. 
2. Subject has a history of plaque psoriasis for at least 6 months prior to the screening visit. 
3. Subject had no significant flare in psoriasis for at least 3 months before screening (information 
obtained from medical chart or subject’s physician, or directly from the subject). 
4. Subject has moderate to severe plaque psoriasis as defined by a PASI score ≥ 12 and a 
PGA score ≥ 3 at screening and Day 1. 
5. Subject has plaque psoriasis covering ≥ 10% of his or her total BSA at screening and Day 1. 
6. Subject must be a candidate for phototherapy or systemic therapy. 
7. For female subjects of childbearing potential involved in any sexual intercourse that could lead 
to pregnancy: the subject must agree to use a highly effective contraceptive method from at 
least 4 weeks prior to Day 1 until at least 4 weeks after the last study product administration. 
Highly effective contraceptive methods include hormonal contraceptives (eg, combined oral 
contraceptive, patch, vaginal ring, injectable, or implant), intrauterine devices or intrauterine 
systems, vasectomized partner(s) (provided vasectomy was performed ≥ 4 months prior to 
DocuSign Envelope ID: 4194D198-F02D-4229-8F23-73031B7F0AC2
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Name of Sponsor/Company: 
Nimbus Lakshmi, Inc. 
Name of Investigational Product: 
NDI-034858 
Name of Active Ingredient: 
NDI-034858 
screening), bilateral tubal ligation or occlusion, or double barrier methods of contraception (eg, 
male condom with cervical cap, male condom with diaphragm, and male condom with 
contraceptive sponge) in conjunction with spermicide.  
Note: Subjects must have been on a stable dose of combined hormonal contraceptives for at least 
4 weeks before Day 1.  
Note: The above list of contraceptive methods does not apply to subjects who are abstinent for at 
least 4 weeks before Day 1 and will continue to be abstinent from penile-vaginal intercourse 
throughout the study. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical study, and the preferred and usual lifestyle of the subject. Periodic 
abstinence (calendar, symptothermal, postovulation methods) is not acceptable. 
Note: A female subject of nonchildbearing potential is defined as follows:  
– 
Female subject who has had surgical sterilization (hysterectomy, bilateral oophorectomy, 
or bilateral salpingectomy); 
– 
Female subject who has had a cessation of menses for at least 12 months prior to the 
screening visit without an alternative medical cause, and a follicle-stimulating hormone 
(FSH) test confirming nonchildbearing potential (refer to laboratory reference ranges for 
confirmatory levels). 
8. Female subjects of childbearing potential have had a negative serum pregnancy test at 
screening and negative urine pregnancy test at Day 1. 
9. For male subjects involved in any sexual intercourse that could lead to pregnancy, subject must 
agree to use one of the highly effective contraceptive methods listed in Inclusion Criterion 7, 
from Day 1 until at least 12 weeks after the last study product administration. If the female 
partner of a male subject uses any of the hormonal contraceptive methods listed above, this 
contraceptive method should be used by the female partner from at least 4 weeks before Day 1 
until at least 12 weeks after the last study product administration. 
Note: Male subjects must refrain from donating sperm from Day 1 until at least 12 weeks after 
the last study product administration. 
Note: No restrictions are required for a male subject who underwent a vasectomy at least 
4 months prior to screening and the procedure is documented. If vasectomy procedure is not 
documented or was performed less than 4 months prior to screening, male subjects must follow 
the same contraception and sperm donation requirements as for nonvasectomized subjects. 
10. Subject has a body mass index (BMI) within the range of 18 to 42 kg/m2, inclusive 
(BMI = weight [kg]/[height (m)]2), and total body weight >50 kg (110 lb). 
11. Subject is willing to participate and is capable of giving informed consent. Note: Consent must 
be obtained prior to any study-related procedures. 
12. Subjects must be willing to comply with all study procedures and must be available for the 
duration of the study. 
Exclusion criteria: 
A subject who meets any of the following criteria at the screening and/or Day 1 visits, as applicable, 
will be excluded from participation in this study: 
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Name of Sponsor/Company: 
Nimbus Lakshmi, Inc. 
Name of Investigational Product: 
NDI-034858 
Name of Active Ingredient: 
NDI-034858 
1. Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant 
during the study.  
2. Subject has evidence of erythrodermic, pustular, predominantly guttate psoriasis, or -drug 
induced psoriasis. 
3. Subject has a history of skin disease or presence of skin condition that, in the opinion of the 
investigator, would interfere with the study assessments. 
4. Subject has immune-mediated conditions commonly associated with psoriasis, such as 
psoriatic arthritis, uveitis, inflammatory bowel disease, that require systemic treatment 
(including corticosteroids, immunosuppressants, or biologics).  
Note: Subjects with immune-mediated conditions that do not require systemic treatment may be 
included in the study. Certain therapies such as NSAIDs may be permitted but should be 
discussed with the Medical Monitor prior to determination of subject eligibility. 
5. Subject has any clinically significant medical condition, evidence of an unstable clinical 
condition (eg, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, 
pulmonary, immunologic, or local active infection/infectious illness), psychiatric condition, or 
vital signs/physical/laboratory/ECG abnormality that would, in the opinion of the investigator, 
put the subject at undue risk or interfere with interpretation of study results. 
6. Subject had a major surgery within 8 weeks prior to Day 1 or has a major surgery planned 
during the study. 
7. Subject has a history of Class III or IV congestive heart failure as defined by New York Heart 
Association Criteria. 
8. Subject has been hospitalized in the past 3 months for asthma, has ever required intubation for 
treatment of asthma, currently require oral corticosteroids for the treatment of asthma, or has 
required more than one short-term (≤ 2 weeks) course of oral corticosteroids for asthma within 
6 months prior to Day 1. 
9. Subject has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1. 
Subjects with successfully treated nonmetastatic cutaneous squamous cell or basal cell 
carcinoma and/or localized carcinoma in situ of the cervix are not to be excluded. 
10. Subject has a history of fever, inflammation, or systemic signs of illness suggestive of systemic 
or invasive infection within 4 weeks prior to Day 1. 
11. Subject has an active bacterial, viral, fungal, mycobacterial infection, or other infection 
(including TB or atypical mycobacterial disease), or any major episode of infection that 
required hospitalization or treatment with intravenous antibiotics within 12 weeks prior to 
Day 1, or oral antibiotics within 4 weeks prior to Day 1.  
12. Subject has a history of chronic or recurrent infectious disease, including but not limited to 
chronic renal infection, chronic chest infection, recurrent urinary tract infection, fungal 
infection (except for superficial fungal infection of the nailbed), or infected skin wounds or 
ulcers. 
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Name of Sponsor/Company: 
Nimbus Lakshmi, Inc. 
Name of Investigational Product: 
NDI-034858 
Name of Active Ingredient: 
NDI-034858 
13. Subject has a history of an infected joint prosthesis or has received antibiotics for a suspected 
infection of a joint prosthesis if that prosthesis has not been removed or replaced. 
14. Subject has active herpes infection, including herpes simplex 1 and 2 and herpes zoster 
(demonstrated on physical examination and/or medical history) within 8 weeks prior to Day 1. 
15. Subject has a history of known or suspected congenital or acquired immunodeficiency state or 
condition that would compromise the subject’s immune status in the opinion of the investigator 
(eg, history of splenectomy, primary immunodeficiency). 
16. Subject has positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B 
core antigens (anti-HBc), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). 
17. Subject has clinical or laboratory evidence of active or latent tuberculosis (TB) infection at 
screening.  
Note: Subjects with a history of active or latent TB will not be included in the study, unless 
documentation of prior and complete anti-TB treatment, appropriate in duration and type 
according to current local country guidelines, can be provided.  
Note: Subject will be evaluated at screening for latent TB infection with a QuantiFERON-TB 
Gold (QFT) test. Latent TB is defined as a positive QFT test or two successive indeterminate 
QFT tests at screening. 
Note: The T-Spot.TB test (TBT)  is an acceptable alternative to the QFT test in regions where 
the TBT is standard practice for tuberculosis screening. The medical monitor should be informed 
prior to using the TBT in place of the QFT test. A negative TBT is required if the QFT test is not 
performed. 
18. Subject with any of the following laboratory values at the screening visit: 
a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values ≥ 3 times the 
upper limit of normal (ULN); 
b. Hemoglobin < 11.0 g/dL (< 110.0 g/L); 
c. White blood cell count < 3.5 x 109/L (< 3500/mm3); 
d. Absolute neutrophil count of < 1.8 x 109/L (< 1800/mm3); 
e. Absolute lymphocyte count of < 1.0 x 109/L (< 1000/mm3); 
f. Platelet count < 100 x 109/L (< 100,000/mm3); 
g. Total bilirubin ˃ 2 times the ULN. 
19. Subjects who have given > 50 ml of blood or plasma within 30 days of screening or > 500 mL 
of blood or plasma within 56 days of screening (during a clinical study or at a blood bank 
donation). 
20. Subject has used any topical medication that could affect psoriasis (including corticosteroids, 
retinoids, vitamin D analogues [such as calcipotriol], JAK inhibitors, or tar) within 2 weeks 
prior to Day 1.  
21. Subject has used any systemic treatment that could affect psoriasis (including oral, intravenous, 
intramuscular, intraarticular, intrathecal, or intralesional corticosteroids; oral retinoids; 
DocuSign Envelope ID: 4194D198-F02D-4229-8F23-73031B7F0AC2
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Name of Sponsor/Company: 
Nimbus Lakshmi, Inc. 
Name of Investigational Product: 
NDI-034858 
Name of Active Ingredient: 
NDI-034858 
immunosuppressive/immunomodulating medication; methotrexate; cyclosporine; oral JAK 
inhibitors; or apremilast) within 4 weeks prior to Day 1.  
Note: Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear drops 
containing corticosteroids are also allowed. 
22. Subject has received any ultraviolet (UV)-B phototherapy (including tanning beds) or excimer 
laser within 4 weeks prior to Day 1. 
23. Subject has had psoralen and ultraviolet A (PUVA) treatment within 4 weeks prior to Day 1. 
24. Subject has received any live-attenuated vaccine within 4 weeks prior to Day 1 or plans to 
receive a live-attenuated vaccine during the study and up to 4 weeks or 5 half-lives of the study 
product, whichever is longer, after the last study product administration.  
Note: Non-live-attenuated vaccines or boosters for Coronavirus Disease 2019 (COVID-19) (eg, 
RNA-based vaccines, inactivated adenovirus-based vaccines, protein-based vaccines) are 
allowed during the study. The study site should follow local guidelines related to COVID-19. 
25. Subject is currently receiving a nonbiological investigational product or device or has received 
one within 4 weeks prior to Day 1. 
26. Subject has received any marketed or investigational biological agent within 12 weeks or 
5 -half-lives (whichever is longer) prior to Day 1 (except those listed in Exclusion Criterion 27 
and 28 that are to be excluded for 6 months). 
27. Subject was previously enrolled in any study with NDI-034858. 
28. Subject has a history of lack of response to any therapeutic agent targeting interleukin (IL)-12, 
IL-17, and/or IL-23 (eg, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, 
tildrakizumab, risankizumab) at approved doses after at least 12 weeks of therapy, and/or 
received one of these therapies within 6 months prior to Day 1. 
29. Subject has received rituximab or other immune cell depleting therapy within 6 months. 
30. Subject is currently being treated with strong or moderate cytochrome P450 3A (CYP3A4) 
inhibitors (such as itraconazole) or has received moderate or strong CYP3A4 inhibitors within 
4 weeks prior to Day 1. 
31. Subject is currently being treated with terbinafine or has received terbinafine within 4 weeks 
prior to Day 1. 
32. Subject has consumed grapefruit within 1 week prior to Day 1. 
Note: Consumption of grapefruit must be avoided during the treatment period and for at least 
1 week after last dose administration. 
33. Subject has used tanning booths within 4 weeks prior to Day 1, has had excessive sun 
exposure, or is not willing to minimize natural and artificial sunlight exposure during the study.  
Note: Use of sunscreen products and protective apparel are recommended when sun exposure 
cannot be avoided. 
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Name of Sponsor/Company: 
Nimbus Lakshmi, Inc. 
Name of Investigational Product: 
NDI-034858 
Name of Active Ingredient: 
NDI-034858 
34. Subject has a known or suspected allergy to NDI-034858 or any component of the 
investigational product, or any other significant drug allergy (such as anaphylaxis or 
hepatotoxicity). 
35. Subject has a known history of clinically significant drug or alcohol abuse in the last year prior 
to Day 1. 
36. For subjects consenting to biopsy collection only:  
– 
Subject has a history of an allergic reaction or significant sensitivity to lidocaine or other 
local anesthetics. 
– 
Subject has a history of hypertrophic scarring or keloid formation in scars or suture sites. 
– 
Subject has taken anticoagulant medication, such as heparin, low molecular weight (LMW) 
heparin, warfarin, or antiplatelet agents (except low-dose aspirin ≤ 81 mg which will be 
allowed), within 2 weeks prior to Day 1, or has a contraindication to skin biopsies. 
Nonsteroidal-anti-inflammatory drugs will not be considered antiplatelet agents and will be 
allowed. 
Statistical methods:  
Categorical variables will be presented in tables as frequencies and percentages. Continuous variables 
will be summarized in tables and will include the number of subjects, mean, standard deviation (SD), 
median, minimum, and maximum.  
Further details regarding the efficacy and safety variable definitions, analyses strategy, statistical 
justification, and techniques for handling missing values (if applicable) will be detailed in a separate 
statistical analysis plan (SAP) that will be prepared before the database is locked and any analyses are 
undertaken. Any deviation(s) from the SAP will be described and justified in the final Clinical Study 
Report, as appropriate. 
All statistical tests will be two-sided and will be performed with a significant level of 0.05, unless 
otherwise specified in the SAP. To account for the multiplicity testing in the primary endpoint analysis, 
each active treatment group will be compared to the placebo group using a hierarchical testing 
procedure, starting with the highest dose group and ending with the lowest dose group (30-mg 
NDI-034858, 15-mg NDI-034858, 5-mg NDI-034858, and 2-mg NDI-034858, in order). No 
adjustment to alpha will be made to account for multiple testing between treatment groups for the 
secondary 
 efficacy endpoints. 
Efficacy Analyses:  
The primary endpoint can be translated as a responder analysis, where a subject will be classified as 
responder if he or she achieves PASI-75 at Week 12. The comparison between groups for the primary 
endpoint will be done using a Cochran-Mantel-Haenszel (CMH), with prior treatment with biologics 
included as a stratification factor. The primary efficacy analysis will be performed on the modified 
intent-to-treat (mITT) analysis set, while the per-protocol (PP) analysis set will be used as a sensitivity 
analysis.  
The secondary endpoints involving proportions of subjects will be analyzed using the same approach 
(CMH test) as described for the primary efficacy analysis, at each time point and based on the mITT 
analysis. 
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Name of Sponsor/Company: 
Nimbus Lakshmi, Inc. 
Name of Investigational Product: 
NDI-034858 
Name of Active Ingredient: 
NDI-034858 
The continuous secondary endpoints involving absolute change from baseline will be analyzed using a 
mixed effect model repeated measures method (MMRM) based on the mITT analysis set only. The 
model will include treatment, visit, treatment by-visit interaction, and prior treatment with biologics as 
fixed effects, and baseline score as a covariate. 
Safety Analyses:  
All safety analyses will be conducted using the safety analysis set. No inferential statistics will be 
performed on safety variables. 
Adverse events and serious adverse events (SAEs) will be presented and tabulated according to the 
Medical Dictionary for Regulatory Activities (MedDRA) classification by treatment group. 
Descriptions of AEs will include the start date, the stop date (if it resolved), the severity and 
seriousness of the AE, the causality of the AE to study product, action taken with respect to the study 
product, and the outcome.  
Reported AEs will be summarized by the number of subjects reporting the events, as well as by system 
organ class, preferred term, reported verbatim severity, seriousness, and investigator’s assessment of 
the relationship to study product. For the summary of AEs by severity, each subject will be counted 
only once within a system organ class or a preferred term by using the AEs with the highest intensity 
within each category for each analysis. For the summary of AEs by relationship to study product, each 
subject will be counted only once within a system organ class or a preferred term by using the AEs 
with the greatest reported relationship within each category. For the summary of AEs by relationship to 
study product and severity, each subject will be counted only once within a system organ class or a 
preferred term by using (1) the greatest reported relationship followed by (2) the highest reported 
intensity.  
All information pertaining to AEs noted during the study will be listed by treatment group, subject, 
detailing verbatim, system organ class, preferred term, start date, stop date, intensity, outcome, action 
taken with respect to study product, and relationship to study product. The AE onset will also be shown 
relative (in number of days) to the day of study product administration. Serious adverse events will be 
tabulated by treatment group, relationship to the test article, and a reference to the occurrence of the 
SAEs to the relative day of dosing. Similar listings will be provided for the SAEs and AEs leading to 
the discontinuation from the study. 
Results from vital signs, laboratory analyses, and ECGs will be tabulated by treatment group and visit 
using descriptive statistics. The observed value at each visit, as well as the change from baseline will 
be presented. Shift tables describing shifts to out-of-normal range will be provided for clinical 
laboratory results, and normal to abnormal shift tables may be provided for vital signs. 
Concomitant medications will be coded with the World Health Organization – Drug Dictionary 
(WHO-DD) and listed by subject. Summary of medications will also be tabulated. 
Pharmacokinetic Analyses: 
Concentration data will be listed per subject and summarized descriptively per dose.  
 
. 
Other Analyses: 
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Name of Sponsor/Company: 
Nimbus Lakshmi, Inc. 
Name of Investigational Product: 
NDI-034858 
Name of Active Ingredient: 
NDI-034858 
Descriptive summaries of subject disposition and baseline characteristics (including demographic data 
and prior concomitant therapy) will be presented by treatment group. In addition, a list of subjects who 
discontinued from the study along with discontinuation reason will be provided. 
Protocol deviations will be summarized by treatment and category. 
Sample Size Consideration: 
The sample size determination is based on testing equality of two independent response rates using a 
2-sided test with significance level of alpha = 0.05 and power 85%. The formula used for the 
calculation is the same as used in the nQuery® (ie, normal approximation with Fleiss’ formula and 
continuity correction). 
Assuming the placebo response rate at end of Week 12 is 10% (proportion of subjects achieving 
PASI-75), at least one of the NDI-034858 dose treatment groups will have a response rate at least 40%, 
and after adjustment of 15% dropout rate, a total of 250 subjects (50 per treatment group) will be 
randomized in the study.  
Fifty subjects per treatment group, with 1-sided, 2-sample Fisher’s exact test at significant level 0.05, 
will provide at least approximately 90% power to detect at least 30% difference in the response rate in 
PASI-75 between any two treatment groups. 
 
 
DocuSign Envelope ID: 4194D198-F02D-4229-8F23-73031B7F0AC2
For non-commercial use only


Protocol Number 4858-201
Protocol Version 3.0: 04-Feb-2022
Confidential
30 of 94
1.2.
Study Diagram
Figure 1:
Study Diagram
Abbreviation: QD, once daily.
1.3.
Schedule of Events
The screening evaluation will only be performed after the subject has agreed to participate and 
has signed and dated the ICF. No treatment or study-related procedures will be initiated before 
the informed consent is signed. The Day 1 visit must be performed, at the latest, 30 days after the 
screening visit.
The screening evaluation will be performed according to the inclusion and exclusion criteria. If 
the subject fulfills all inclusion criteria and no exclusion criteria, he or she may be included in 
the study.
Table 1 provides a description of the procedures to be performed at each visit.
Unless specified otherwise, the study assessments scheduled during the treatment period must be 
performed before study product administration, if applicable (no drug administration the day of 
Week 12 visit).
,7190 436Ā- 6:25782Ā/,( Ā$!'$,!'&Ȁ.
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For non-commercial use only


Protocol Number 4858-201 
Protocol Version 3.0: 04-Feb-2022 
 
Confidential 
31 of 94 
Quality of life assessment (DLQI), 
 
 must be completed prior to other efficacy assessments (PASI, PGA, 
 
). 
The COVID-19 pandemic may impact the ability to adhere to the study procedures described in 
Table 1 due to challenges that include, but are not limited to, subject preferences, site closures, 
travel restrictions, and quarantines. Please refer to Section 4.2 for more details on allowable, as 
necessary, modifications to the protocol due to COVID-19 restrictions. 
Every attempt should be made to adhere to the visit schedule. If an unscheduled visit (eg, an 
additional visit not specified in Table 1) is unavoidable or necessary, the investigator may allow 
it at his or her discretion. All study-specific unscheduled visits should be documented in the 
subjects record and the appropriate clinical data should be entered into the Electronic Data 
Capture (EDC).
DocuSign Envelope ID: 4194D198-F02D-4229-8F23-73031B7F0AC2
For non-commercial use only


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Protocol Number 4858-201 
Protocol Version 3.0: 04-Feb-2022 
Confidential 
34 of 94 
Study Visits 
Screening Period 
Treatment Period 
Follow-up 
or Early 
Termination 
 
Screening 
Visit 
Day 
-7a 
Day 1 
Week 1 Week 2 
Week 4 
Week 8 
Week 
12/End of 
Treatment 
Week 16 
Windows (days) 
-30 to -8 
(±1) 
 
(±2) 
(±2) 
(±2) 
(±3) 
(±3) 
(±4) 
 
.  
q At certain study sites, in a subset of subjects who consent, optional medical photographs of full body, front and back, will be taken. 
r Adverse events evaluation begins after dosing on Day 1. 
Note: Unscheduled visits are described in Section 1.3. 
 
DocuSign Envelope ID: 4194D198-F02D-4229-8F23-73031B7F0AC2
For non-commercial use only


Protocol Number 4858-201 
Protocol Version 3.0: 04-Feb-2022 
 
Confidential 
35 of 94 
2. 
INTRODUCTION 
2.1. 
Background 
2.1.1. 
Plaque Psoriasis 
Plaque psoriasis is a chronic inflammatory skin disorder characterized by thickened and inflamed 
areas of skin. These plaque regions exhibit a confluent parakeratotic scale, loss of the granular 
cell layer, increased number of epidermal cell layers, and prominent lymphocyte infiltration.1 
Markers of inflammation and specific immune cell subsets are highly elevated in psoriatic 
plaques. This includes elevated mRNA and protein levels of IL-23 / T helper (Th) 17 activity 
(such as IL-23, IL-17A, IL-17F, and IL-22), elevated markers of keratinocyte activation and 
proliferation, and markers of infiltrating immune cells.2  
Plaque psoriasis is a prevalent disease worldwide, with 1-2% of people affected, and its severity 
is generally categorized based on PASI, total BSA affected, and PGA.3,4 The primary goal of 
psoriasis therapies is clearance of psoriatic plaques, and the benchmark level of treatment 
response in most current clinical studies is PASI-75 at Week 12 or 16. This benchmark is readily 
achieved by the majority of patients treated with biologic therapies targeting tumor necrosis 
factor (TNF)-α, IL-12/23, IL-23, and IL-17.5 
While there are multiple biologic agents approved for the treatment of moderate to severe plaque 
psoriasis, there are a very limited number of oral small molecule therapies available to patients. 
Some patients can be treated with oral immunosuppressive drugs; however these treatments 
generally exhibit limited efficacy.6 The only other approved oral agent for the treatment of 
plaque psoriasis is a phosphodiesterase Type 4 (PDE4) inhibitor (apremilast), which is generally 
safe but exhibits significantly lower efficacy than most biologic therapies and has recognized 
tolerability liabilities including severe diarrhea, nausea, and vomiting in some patients.5,7,8 
2.1.2. 
NDI-034858 
NDI-034858 is a small molecule allosteric inhibitor that binds to the JH2 pseudokinase domain 
of tyrosine kinase 2 (TYK2), leading to inhibition of the TYK2 catalytic JH1 kinase domain and 
subsequent downstream signaling events. The allosteric interaction of NDI-034858 with the 
TYK2 JH2 domain results in highly selective inhibition of TYK2 kinase activity compared to the 
other homologous proteins in the Janus kinase (JAK) family of nonreceptor tyrosine kinases 
(JAK1, JAK2, and JAK3).  
Tyrosine kinase 2 (TYK2) catalyzes the phosphorylation of signal transducers and activators of 
transcription (STAT) proteins downstream of several cytokine receptors, including the IL-23 
receptor, as well as the Type I interferon receptor and the IL-12 receptor.9 The activation of 
TYK2 dependent receptors by their cytokine ligands results in the activation of 
STAT---dependent transcription and cellular functional responses specific for the receptors and 
cell types they are expressed on.10 The cytokine signaling pathways regulated by TYK2 play key 
roles in several immune-mediated disorders. Most relevant for psoriasis pathogenesis, the 
DocuSign Envelope ID: 4194D198-F02D-4229-8F23-73031B7F0AC2
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Protocol Number 4858-201 
Protocol Version 3.0: 04-Feb-2022 
 
Confidential 
43 of 94 
Efficacy data from the Phase 1 Study 4858-102 suggest the therapeutic potential of NDI-034858 
in moderate to severe plaque psoriasis. This is supported by Phase 2b and Phase 3 studies from 
deucravacitinib which validated blockade of TYK2 as a therapeutic approach for treatment of 
moderate to severe plaque psoriasis.   
In summary, the collective preclinical and clinical evidence supporting the inhibition of TYK2 as 
a therapeutic approach in psoriasis and the safety profile of NDI-034858 established to date in 
healthy volunteers and psoriasis subjects provide a strong scientific and clinical rationale for 
pursuing development of NDI-034858 in subjects with moderate to severe plaque psoriasis. The 
benefit/risk for further development of NDI-034858 in psoriasis is therefore warranted. 
DocuSign Envelope ID: 4194D198-F02D-4229-8F23-73031B7F0AC2
For non-commercial use only


Protocol Number 4858-201 
Protocol Version 3.0: 04-Feb-2022 
 
Confidential 
44 of 94 
3. 
OBJECTIVES AND ENDPOINTS 
OBJECTIVES 
ENDPOINTS 
Primary Objective 
To assess the efficacy of 
NDI-034858 orally 
administered QD at 2 mg, 5 
mg, 15 mg, or 30 mg for 
12 weeks in subjects with 
moderate to severe plaque 
psoriasis 
Primary Efficacy Endpoint 
• Proportion of subjects achieving PASI-75 at Week 12 
Secondary Efficacy Endpoints 
• Proportion of subjects achieving a PGA of clear (0) or almost clear (1) at 
Week 12 
• Proportion of subjects achieving at least PASI-90 at Week 12 
• Proportion of subjects achieving at least PASI-100 at Week 12 
• Change from baseline in DLQI at Week 12 
Exploratory 
 Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DocuSign Envelope ID: 4194D198-F02D-4229-8F23-73031B7F0AC2
For non-commercial use only


Protocol Number 4858-201 
Protocol Version 3.0: 04-Feb-2022 
 
Confidential 
45 of 94 
OBJECTIVES 
ENDPOINTS 
Secondary Objectives 
To assess the safety and 
tolerability of NDI-034858 
orally administered QD at 2 mg, 
5 mg, 15 mg, or 30 mg for 
12 weeks in subjects with 
moderate to severe plaque 
psoriasis 
Secondary Safety Endpoints 
• Incidence of AEs 
• Changes in vital signs, clinical laboratory parameters, and ECGs 
To evaluate the plasma 
concentration of NDI-034858 
orally administered QD at 2 
mg, 5 mg, 15 mg, or 30 mg 
in subjects with moderate to 
severe plaque psoriasis 
Secondary Pharmacokinetic Endpoint 
• Measurement of plasma concentrations of NDI-034858 in subjects 
receiving active treatment  
 
 
 
 
 
 
 
Exploratory 
 Endpoints 
 
 
 
 
 
 
 
 
Exploratory 
 Endpoints 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AE, adverse event; 
; DLQI, Dermatology Life Quality Index; 
ECG, electrocardiogram; 
; PASI, Psoriasis Area 
and Severity Index; PASI-100, 100% improvement from baseline in PASI; 
 
; PASI-75, 75% improvement from baseline in PASI; PASI-90, 90% improvement from baseline 
in PASI; PGA, Physician’s Global Assessment; QD, once daily. 
 
 
DocuSign Envelope ID: 4194D198-F02D-4229-8F23-73031B7F0AC2
For non-commercial use only


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Protocol Number 4858-201 
Protocol Version 3.0: 04-Feb-2022 
 
Confidential 
47 of 94 
 
  
 
 
 
 
 
 
 
 
 
 
. 
At certain study sites, in a subset of subjects who consent, optional medical photographs of full-
body, front and back, will be taken to illustrate the outcome of the study. 
No interim analysis is planned in this study. 
4.2. 
Study Conduct During the Coronavirus Disease 2019 Pandemic 
Because of the COVID-19 pandemic that has had a worldwide impact, including in North 
America, control measures in place in different regions may impact the ability to adhere to some 
of the study procedures described in this protocol. Due to challenges that include, but are not 
limited to, subject preferences, site closures, travel restrictions, and quarantines, some 
modifications to study conduct during the COVID-19 pandemic may be necessary to ensure 
study continuity.   
The following are allowable, as necessary, modifications to study conduct during the COVID-19 
pandemic. 
• Prior to a study visit at the study site, the subject may be contacted and screened for 
potential exposure or infection to COVID-19 per site, local, or federal requirements. 
If the subject is suspected to be exposed or infected with COVID-19, the on-site visit 
should either be rescheduled or a virtual visit may be performed instead, as applicable 
(refer to Section 7.1 and Section 7.2 for details on subject discontinuation from study 
treatment and study, respectively).   
• If a subject cannot attend their regularly scheduled study visits in person due to 
COVID-19 necessitating a limit on in-person contact, the investigator may perform 
safety and other feasible assessments by phone or video, except for the screening, 
Day 1, and Week 12 visits. If the screening visit cannot be performed on-site, the 
subject should not be screened. If the Day 1 visit cannot be performed on-site, the 
subject should be considered to have failed screening. Subjects who failed screening 
DocuSign Envelope ID: 4194D198-F02D-4229-8F23-73031B7F0AC2
For non-commercial use only


Protocol Number 4858-201 
Protocol Version 3.0: 04-Feb-2022 
 
Confidential 
48 of 94 
due to COVID-19 restrictions at screening or Day 1 may be rescreened at a later time, 
if feasible.  
• Protocol deviations due to missed study visits, missed doses, or missed study 
procedures as well as study discontinuations due to COVID-19 restrictions should be 
documented accordingly. 
• Subjects should continue recording their study product administration via the Diary. 
Safety must be assessed during the virtual visit by collecting AEs and concomitant 
medications. Other safety or efficacy assessments may be performed as reasonably 
practicable.   
• Clinical laboratory tests (serum chemistries, hematology, and urinalysis) and 
pregnancy tests may be performed in local laboratory if these procedures cannot be 
performed at the study site due to COVID-19 related limitations, including but not 
limited to site closure. Clinically significant abnormal laboratory results should be 
promptly communicated to the medical monitor within 72 hours of receipt, as per 
investigator’s judgment. Subjects’ anonymity must be maintained when 
communicating results to the medical monitor. 
• Source documentation should note that the visit was performed virtually (not --face-
to-face) and note the name of the local laboratories where laboratory tests were done. 
• In the case of virtual visits, where the subject is unable to attend the scheduled visits 
due to extenuating circumstances, such as quarantine or immobilization, study 
product may be shipped direct-to-subject from the site. Direct--to-subject shipments 
should only occur if the investigator deems it safe for the subject to continue study 
drug treatment. In all cases, requirements under local regulations for maintaining 
required study product storage conditions and study product accountability remain. 
A detailed assessment of COVID-19 related risk and mitigation measures will be documented in 
the appropriate study plans. 
4.3. 
Scientific Rationale for Study Design  
The proposed design is considered appropriate for assessing the efficacy, safety, and tolerability 
of NDI-034858 (at 2 mg, 5 mg, 15 mg, or 30 mg) compared with placebo in subjects with 
moderate to severe plaque psoriasis.  
This Phase 2b study will be randomized to ensure random allocation of subjects to treatment 
groups to reduce bias. Randomization will be stratified based on prior treatment with biologics. 
Because efficacy assessments of plaque psoriasis have a high degree of subjectivity, the study 
will be double-blinded. The highest degree of subject and study site assessor blinding should be 
sought to achieve credible inference. It is also important to have a placebo control in this Phase 
2b study to control for confounding factors, such as potential investigator bias, and to ensure that 
the statistical procedures can be appropriately applied. 
DocuSign Envelope ID: 4194D198-F02D-4229-8F23-73031B7F0AC2
For non-commercial use only


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Protocol Number 4858-201 
Protocol Version 3.0: 04-Feb-2022 
 
Confidential 
50 of 94 
4.5. 
End of Study Definition 
A subject is considered to have completed the study if he or she has completed all phases of the 
study, including the last visit or the last scheduled procedure shown in the Schedule of Events, 
Table 1. 
The end of the study is defined as completion of the last visit or procedure shown in the schedule 
of event for the last enrolled subject in the study globally for all study sites. 
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5. 
STUDY POPULATION  
5.1. 
Inclusion Criteria 
In order to be eligible to participate in this study, a subject must meet all of the following criteria, 
either at the screening and Day 1 visits or only at one of the specified visits (screening or Day 1) 
as noted in the criterion: 
1. Male or female subject aged 18 to 70 years, inclusive, at the time of consent. 
2. Subject has a history of plaque psoriasis for at least 6 months prior to the screening visit. 
3. Subject had no significant flare in psoriasis for at least 3 months before screening 
(information obtained from medical chart or subject’s physician, or directly from the 
subject). 
4. Subject has moderate to severe plaque psoriasis as defined by a PASI score ≥ 12 and a 
PGA score ≥ 3 at screening and Day 1. 
5. Subject has plaque psoriasis covering ≥ 10% of his or her total BSA at screening and 
Day 1. 
6. Subject must be a candidate for phototherapy or systemic therapy. 
7. For female subjects of childbearing potential involved in any sexual intercourse that 
could lead to pregnancy: the subject must agree to use a highly effective contraceptive 
method from at least 4 weeks prior to Day 1 until at least 4 weeks after the last study 
product administration. Highly effective contraceptive methods include hormonal 
contraceptives (eg, combined oral contraceptive, patch, vaginal ring, injectable, or 
implant), intrauterine devices or intrauterine systems, vasectomized partner(s) (provided 
vasectomy was performed ≥ 4 months prior to screening), bilateral tubal ligation or 
occlusion, or double barrier methods of contraception (eg, male condom with cervical 
cap, male condom with diaphragm, and male condom with contraceptive sponge) in 
conjunction with spermicide.  
Note: Subjects must have been on a stable dose of combined hormonal contraceptives for 
at least 4 weeks before Day 1.  
Note: The above list of contraceptive methods does not apply to subjects who are abstinent 
for at least 4 weeks before Day 1 and will continue to be abstinent from penile-vaginal 
intercourse throughout the study. The reliability of sexual abstinence needs to be evaluated 
in relation to the duration of the clinical study, and the preferred and usual lifestyle of the 
subject. Periodic abstinence (calendar, symptothermal, postovulation methods) is not 
acceptable. 
Note: A female subject of nonchildbearing potential is defined as follows:  
– 
Female subject who has had surgical sterilization (hysterectomy, bilateral 
oophorectomy, or bilateral salpingectomy); 
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– 
Female subject who has had a cessation of menses for at least 12 months prior to the 
screening visit without an alternative medical cause, and an FSH test confirming 
nonchildbearing potential (refer to laboratory reference ranges for confirmatory 
levels). 
8. Female subjects of childbearing potential have had a negative serum pregnancy test at 
screening and negative urine pregnancy test at Day 1. 
9. For male subjects involved in any sexual intercourse that could lead to pregnancy, subject 
must agree to use one of the highly effective contraceptive methods listed in Inclusion 
Criterion 7, from Day 1 until at least 12 weeks after the last study product administration. 
If the female partner of a male subject uses any of the hormonal contraceptive methods 
listed above, this contraceptive method should be used by the female partner from at least 
4 weeks before Day 1 until at least 12 weeks after the last study product administration. 
Note: Male subjects must refrain from donating sperm from Day 1 until at least 12 weeks 
after the last study product administration. 
Note: No restrictions are required for a male subject who underwent a vasectomy at least 
4 months prior to screening and the procedure is documented. If vasectomy procedure is 
not documented or was performed less than 4 months prior to screening, male subjects 
must follow the same contraception and sperm donation requirements as for 
nonvasectomized subjects. 
10. Subject has a BMI within the range of 18 to 42 kg/m2, inclusive (BMI = weight 
[kg]/[height (m)]2), and total body weight >50 kg (110 lb). 
11. Subject is willing to participate and is capable of giving informed consent. Note: Consent 
must be obtained prior to any study-related procedures. 
12. Subjects must be willing to comply with all study procedures and must be available for 
the duration of the study. 
5.2. 
Exclusion Criteria 
A subject who meets any of the following criteria at the screening and/or Day 1 visits, as 
applicable, will be excluded from participation in this study: 
1. Subject is a female who is breastfeeding, pregnant, or who is planning to become 
pregnant during the study.  
2. Subject has evidence of erythrodermic, pustular, predominantly guttate psoriasis, or 
drug-induced psoriasis. 
3. Subject has a history of skin disease or presence of skin condition that, in the opinion of 
the investigator, would interfere with the study assessments. 
4. Subject has immune-mediated conditions commonly associated with psoriasis, such as 
psoriatic arthritis, uveitis, inflammatory bowel disease, that require systemic treatment 
(including corticosteroids, immunosuppressants, or biologics).  
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Note: Subjects with immune-mediated conditions that do not require systemic treatment 
may be included in the study. Certain therapies such as NSAIDs may be permitted but 
should be discussed with the Medical Monitor prior to determination of subject eligibility. 
5. Subject has any clinically significant medical condition, evidence of an unstable clinical 
condition (eg, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, 
pulmonary, immunologic, or local active infection/infectious illness), psychiatric 
condition, or vital signs/physical/laboratory/ECG abnormality that would, in the opinion 
of the investigator, put the subject at undue risk or interfere with interpretation of study 
results. 
6. Subject had a major surgery within 8 weeks prior to Day 1 or has a major surgery 
planned during the study. 
7. Subject has a history of Class III or IV congestive heart failure as defined by New York 
Heart Association Criteria. 
8. Subject has been hospitalized in the past 3 months for asthma, has ever required 
intubation for treatment of asthma, currently require oral corticosteroids for the treatment 
of asthma, or has required more than one short-term (≤ 2 weeks) course of oral 
corticosteroids for asthma within 6 months prior to Day 1. 
9. Subject has a history of cancer or lymphoproliferative disease within 5 years prior to 
Day 1. Subjects with successfully treated nonmetastatic cutaneous squamous cell or basal 
cell carcinoma and/or localized carcinoma in situ of the cervix are not to be excluded. 
10. Subject has a history of fever, inflammation, or systemic signs of illness suggestive of 
systemic or invasive infection within 4 weeks prior to Day 1. 
11. Subject has an active bacterial, viral, fungal, mycobacterial infection, or other infection 
(including TB or atypical mycobacterial disease), or any major episode of infection that 
required hospitalization or treatment with intravenous antibiotics within 12 weeks prior to 
Day 1, or oral antibiotics within 4 weeks prior to Day 1.  
12. Subject has a history of chronic or recurrent infectious disease, including but not limited 
to chronic renal infection, chronic chest infection, recurrent urinary tract infection, fungal 
infection (except for superficial fungal infection of the nailbed), or infected skin wounds 
or ulcers. 
13. Subject has a history of an infected joint prosthesis or has received antibiotics for a 
suspected infection of a joint prosthesis if that prosthesis has not been removed or 
replaced. 
14. Subject has active herpes infection, including herpes simplex 1 and 2 and herpes zoster 
(demonstrated on physical examination and/or medical history) within 8 weeks prior to 
Day 1. 
15. Subject has a history of known or suspected congenital or acquired immunodeficiency 
state or condition that would compromise the subject’s immune status in the opinion of 
the investigator (eg, history of splenectomy, primary immunodeficiency). 
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16. Subject has positive results for HbsAg, anti-HBc, HCV, or HIV. 
17. Subject has clinical or laboratory evidence of active or latent TB infection at screening.  
Note: Subjects with an history of active or latent TB will not be included in the study, 
unless documentation of prior and complete anti-TB treatment, appropriate in duration and 
type according to current local country guidelines, can be provided.  
Note: Subject will be evaluated at screening for latent TB infection with a QFT test. Latent 
TB is defined as a positive QFT test or two successive indeterminate QTF tests at 
screening.  
Note: The T-Spot.TB test (TBT)  is an acceptable alternative to the QFT test in regions 
where the TBT  is standard practice for tuberculosis screening. The medical monitor 
should be informed prior to using the TBT test in place of the QFT test. A negative TBT 
test is required if the QFT test is not performed. 
 
18. Subject with any of the following laboratory values at the screening visit: 
a. ALT or AST values ≥ 3 times the ULN; 
b. Hemoglobin < 11.0 g/dL (< 110.0 g/L); 
c. White blood cell count < 3.5 x 109/L (< 3500/mm3); 
d. Absolute neutrophil count of < 1.8 x 109/L (< 1800/mm3); 
e. Absolute lymphocyte count of < 1.0 x 109/L (< 1000/mm3); 
f. Platelet count < 100 x 109/L (< 100,000/mm3); 
g. Total bilirubin ˃ 2 times the ULN. 
19. Subjects who have given > 50 ml of blood or plasma within 30 days of screening or 
> 500 mL of blood or plasma within 56 days of screening (during a clinical study or at a 
blood bank donation). 
20. Subject has used any topical medication that could affect psoriasis (including 
corticosteroids, retinoids, vitamin D analogues [such as calcipotriol], JAK inhibitors, or 
tar) within 2 weeks prior to Day 1.  
21. Subject has used any systemic treatment that could affect psoriasis (including oral, 
intravenous, intramuscular, intraarticular, intrathecal, or intralesional corticosteroids; oral 
retinoids; immunosuppressive/immunomodulating medication; methotrexate; 
cyclosporine; oral JAK inhibitors; or apremilast) within 4 weeks prior to Day 1.  
Note: Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear drops 
containing corticosteroids are also allowed. 
22. Subject has received any UV-B phototherapy (including tanning beds) or excimer laser 
within 4 weeks prior to Day 1. 
23. Subject has had PUVA treatment within 4 weeks prior to Day 1. 
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24. Subject has received any live-attenuated vaccine within 4 weeks prior to Day 1 or plans 
to receive a live-attenuated vaccine during the study and up to 4 weeks or 5 half-lives of 
the study product, whichever is longer, after the last study product administration.  
Note: Non-live-attenuated vaccines or boosters for COVID-19 (eg, RNA-based vaccines, 
inactivated adenovirus-based vaccines, protein-based vaccines) are allowed during the 
study. The study site should follow local guidelines related to COVID-19. 
25. Subject is currently receiving a nonbiological investigational product or device or has 
received one within 4 weeks prior to Day 1. 
26. Subject has received any marketed or investigational biological agent within 12 weeks or 
5 half-lives (whichever is longer) prior to Day 1 (except those listed in Exclusion 
Criterion 27 and 28 that are to be excluded for 6 months). 
27. Subject was previously enrolled in any study with NDI-034858. 
28. Subject has a history of lack of response to any therapeutic agent targeting IL-12, IL-17, 
and/or IL-23 (eg, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, 
tildrakizumab, risankizumab) at approved doses after at least 12 weeks of therapy, and/or 
received one of these therapies within 6 months prior to Day 1. 
29. Subject has received rituximab or other immune-cell depleting therapy within 6 months. 
30. Subject is currently being treated with strong or moderate cytochrome P450 3A 
(CYP3A4) inhibitors (such as itraconazole, refer to Appendix 1), or has received 
moderate or strong CYP3A4 inhibitors within 4 weeks prior to Day 1. 
31. Subject is currently being treated with terbinafine or has received terbinafine within 
4 weeks prior to Day 1. 
32. Subject has consumed grapefruit within 1 week prior to Day 1. 
Note: Consumption of grapefruit must be avoided during the treatment period and for at 
least 1 week after last dose administration. 
33. Subject has used tanning booths within 4 weeks prior to Day 1, has had excessive sun 
exposure, or is not willing to minimize natural and artificial sunlight exposure during the 
study.  
Note: Use of sunscreen products and protective apparel are recommended when sun 
exposure cannot be avoided. 
34. Subject has a known or suspected allergy to NDI-034858 or any component of the 
investigational product, or any other significant drug allergy (such as anaphylaxis or 
hepatotoxicity). 
35. Subject has a known history of clinically significant drug or alcohol abuse in the last year 
prior to Day 1. 
36. For subjects consenting to biopsy collection only:  
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– 
Subject has a history of an allergic reaction or significant sensitivity to lidocaine or 
other local anesthetics. 
– 
Subject has a history of hypertrophic scarring or keloid formation in scars or suture 
sites. 
– 
Subject has taken anticoagulant medication, such as heparin, LMW-heparin, warfarin, 
or antiplatelet agents (except low-dose aspirin ≤ 81 mg which will be allowed), within 
2 weeks prior to Day 1, or has a contraindication to skin biopsies. Nonsteroidal anti-
inflammatory drugs will not be considered antiplatelet agents and will be allowed. 
5.3. 
Screen Failures 
Screen failures are defined as individuals who consent to participate in the clinical study but are 
not subsequently randomly assigned to the study treatment. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure subjects, to meet the 
Consolidated Standards of Reporting Trials publishing requirements, and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details, 
and eligibility criteria. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once, if deemed acceptable by the investigator. Rescreened subjects should be 
assigned a different subject number than the initial screening. All procedures planned at the 
screening visit, including signature of a new consent form, will be performed. 
 
 
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6. 
TREATMENT 
6.1. 
Study Treatment Administered 
This study involves a comparison of NDI-034858 at 2 mg, 5 mg, 15 mg, or 30 mg orally 
administered QD with a placebo. NDI-034858 will be available in 2 mg, 5 mg, and 15 mg 
strength capsules. All study products will be provided by the sponsor. 
All study products will be administered orally daily, as assigned, for 12 weeks. On study days, 
the study products will be administered at the study site (if applicable). The date and time of the 
drug administration will be collected daily by the study site (during the visit) or via a diary 
provided to the subject. The subject should be instructed to take the study product at 
approximately the same time of the day. For Day 1 and Week 12 visits, subjects should be fasted 
for at least 8 hours before their visit and up to the time of the blood draw for fasting lipid panel.  
Further details regarding the study products can be found in Table 3. 
Table 3: 
Study Treatments 
 
Study Products 
Product name 
NDI-034858  
NDI-034858  
NDI-034858  
NDI-034858  
Placebo 
Dosage form 
Capsule 
Capsule 
Capsule 
Capsule 
Capsule 
Unit dose 
strength(s) 
2 mg  
5 mg  
15 mg  
15 mg  
N/A 
Dosage level(s) 
2 mg 
5 mg 
15 mg 
30 mg 
N/A 
Number of 
capsules per 
dose level 
1 active 
1 placebo 
1 active  
1 placebo 
1 active  
1 placebo 
2 active  
2 placebo 
Route of 
administration  
Oral 
Oral 
Oral 
Oral 
Oral 
Dosing 
instructions 
QD with 
approximately 
240 mL of 
water 
QD with 
approximately 
240 mL of 
water 
QD with 
approximately 
240 mL of 
water 
QD with 
approximately 
240 mL of 
water 
QD with 
approximately 
240 mL of water 
Physical 
description 
Opaque white 
capsules 
Opaque white 
capsules 
Opaque white 
capsules 
Opaque white 
capsules 
Placebo is 
identical to the 
active capsules in 
size, shape, and 
color. 
Source of 
procurement 
Nimbus 
Lakshmi, Inc. 
Nimbus 
Lakshmi, Inc. 
Nimbus 
Lakshmi, Inc. 
Nimbus 
Lakshmi, Inc. 
Nimbus 
Lakshmi, Inc. 
Abbreviations: N/A, not applicable; QD, once daily. 
The contents of the label will be in accordance with all applicable regulatory requirements. 
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6.2. 
Preparation/Handling/Storage/Accountability 
6.2.1. 
Preparation/Storage/Handling  
All study products must be stored in a secure environmentally controlled and monitored area in 
accordance with the labelled storage conditions with access limited to the investigator and 
authorized site staff. The study products may only be supplied by authorized site staff and may 
only be given to subjects enrolled into the study.   
Study products will be dispensed by the study site to the subject at the visits specified in Table 1. 
Subjects are to return all study products (used and unused) to the study site. The capsules will be 
counted prior to dispensing and upon return, and the counts will be recorded in the source 
documents and electronic case report form (eCRF). Each subject will be instructed on the 
importance of returning study product at the next study visit and on taking the product as 
prescribed. If a subject does not return study product, he or she will be instructed to return it as 
soon as possible. 
6.2.2. 
Accountability  
The investigator is responsible for maintaining accurate records of the study product received 
initially and of the study product dispensed/used. Any study product accidentally or deliberately 
destroyed or returned to the sponsor or designee will be accounted for. Any discrepancies 
between amounts dispensed and returned will be explained. At the conclusion of the study, all 
used and unused investigational products, and all medication containers will be returned or 
destroyed as per approved arrangements by the sponsor.   
All study product accountability forms and treatment logs must be retained in the investigator’s 
study files. Product inventory and accountability records will be maintained, as per ICH GCP. 
These records must be available for inspection at any time by the sponsor, its designees, or by 
regulatory agencies. 
Further guidance and information for final disposition of study products are provided in the study 
manual. 
6.3. 
Randomization 
At the study site, each screened subject will be assigned a subject identifier number during 
screening that will be used on all subject documentation. The subject identifier number will 
contain the site number and the subject number and will be assigned in numerical order at the 
screening visit based on chronological order of screening dates (eg, 02-010 for the 10th subject 
screened at Site 02). 
Approximately 250 subjects will be randomized 1:1:1:1:1 ratio to NDI-034858 at 2 mg, 5 mg, 
15 mg, or 30 mg, or placebo (approximately 50 subjects per treatment group).  
Randomization will occur at Day -7 visit. Before Day -7, available eligibility information will be 
reviewed and Subject Eligibility Form will be submitted for approval. Subject will then be 
randomized.  The randomization list will be generated using validated software and will be 
stratified based on prior treatment with biologics (yes/no). The master randomization list will be 
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kept secured until the study blind is broken at the end of study. This list will be uploaded into an 
Interactive Web Response System (IWRS). The investigator or designee will be able to acquire a 
randomization number for subjects by connecting to the IWRS. Of note, only eligible subjects 
(confirmed on Day 1) will receive the study treatment.  
A cap on the number of subjects to include for optional biopsy collection and optional tape strips 
will be placed between 30% to 50% and 40% to 60%, respectively. 
Further guidance and information can be obtained in the study manual. 
6.3.1. 
Blinding 
This study will be double-blinded. At all times, treatment and randomization information will be 
kept confidential and will not be released to the investigator, the study staff, the contract research 
organization (CRO), or the sponsor’s study team until after the conclusion of the study. 
Breaking the blind should be considered only when knowledge of the treatment assignment is 
deemed essential for the subject’s care. In such case of a medical emergency, the investigator has 
the sole responsibility for determining if unblinding of a subject’s treatment assignment is 
warranted. Subject safety must always be the first consideration in making such a determination. 
If the investigator decides that unblinding is warranted, the investigator should make every effort 
to contact the medical monitor prior to unblinding a subject’s treatment assignment unless this 
could delay further management of the subject. If a subject’s treatment assignment is unblinded, 
the medical monitor and the sponsor must be notified within 24 hours after breaking the blind. 
The date and reason for breaking the blind must be documented in the source document and the 
eCRF.  
In cases of accidental unblinding, the investigator should contact the medical monitor and ensure 
every attempt is made to preserve the blind. Any request to unblind a subject for nonemergency 
purposes must be discussed with the medical monitor prior to unblinding. 
The subject for whom the blind has been broken for a safety-related reason will be permanently 
discontinued from the study treatment. The primary reason for study treatment discontinuation 
(the event or condition which led to the unblinding) will be recorded. 
6.3.2. 
Study Treatment Compliance 
Study treatment compliance will be monitored at each visit. Adherence to treatment will be 
assessed by direct questioning, review of the subject’s dosing diary, and by maintaining adequate 
study product dispensing and return records.  
Subjects who are significantly noncompliant with treatment will be counseled and could be 
discontinued from the study, at the discretion of the investigator, following consultation with the 
sponsor. Significant noncompliance is defined as missing 3 consecutive doses (ie, 3 days in a 
row) or missing a total of 10 doses, or an overdose as defined in Section 8.4.10.  
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6.4. 
Concomitant Therapy 
All medications (including over-the-counter drugs, vitamins, herbal/natural products, and 
antacids) taken within 4 weeks prior to screening and throughout the study must be recorded. In 
addition, the last use of any prohibited medications before Day 1 must be recorded and fall 
within the timeframe described in the exclusion criteria. 
Medication entries may be captured as generic or trade names. Trade names should be used for 
combination drugs. Entries should include as much as possible of the following information: the 
dose, unit, frequency of administration, route of administration, start date, end date, and 
indication. If the medication is stopped or the dosage is changed, these details must be recorded. 
6.4.1. 
Permitted Therapies 
6.4.1.1. 
Emollients  
Subjects can apply an emollient of their choice (except those containing salicylic acid) on their 
skin, including on psoriasis lesions. However, on the day of scheduled visits, subjects cannot 
apply emollient before their scheduled visit time. 
Every effort should be made to keep the same emollient throughout the study for the same body 
region. However, the chosen emollient may differ depending on the body region (eg, body vs 
face emollient may be different). The commercial name of the selected emollient(s) will be 
recorded in the source document and the eCRF. No other products may be applied to the lesions 
during the study. 
6.4.1.2. 
Other Permitted Therapies 
The following therapies are permitted: 
• Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear drops 
containing corticosteroids are also allowed.   
• Use of sunscreen products and protective apparel are permitted when sun exposure 
cannot be avoided. However, on the day of scheduled visits, subjects cannot apply 
sunscreen products before their scheduled visit time. 
6.4.2. 
Prohibited Therapies or Procedures 
Table 4 lists prohibited medications that are not to be used from the defined washout periods 
before the first administration of study treatment at the Day 1 visit through the last study visit. 
Subjects who start prohibited medications (systemic and topical) or therapies during the study 
may be discontinued from study treatment. Section 7.1 provides the list of prohibited 
medications for which a subject must be permanently discontinued from the study. Investigators 
should contact the medical monitor as soon as possible when any prohibited medication or 
therapy is initiated, to discuss the appropriate steps.  
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Table 4: 
Prohibited Therapies or Procedures 
Prohibited Medications, Products, And Procedures 
Washout Period Prior 
To First Dose (Day 1)  
Therapeutic agent targeting IL-12, IL-17, and/or IL-23 (eg, ustekinumab, 
secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, 
risankizumab) 
6 months 
Rituximab or other immune-cell depleting agents 
6 months 
Any marketed or investigational biological agent (except those listed 
above) 
12 weeks or 5 half-lives 
(whichever is longer) 
Intravenous antibiotic treatment 
12 weeks 
Oral antibiotic treatment 
4 weeks 
Nonbiological investigational product or device  
4 weeks 
Any live-attenuated vaccine 
Note: Non-live-attenuated vaccines or boosters for COVID-19 (eg, RNA-
based vaccines, inactivated adenovirus-based vaccines, protein-based 
vaccines) are allowed during the study. The study site should follow local 
guidelines related to COVID-19. 
4 weeks 
Systemic treatment that could affect psoriasis (including oral, 
intravenous, intramuscular, intraarticular, intrathecal, or intralesional 
corticosteroids; oral retinoids; immunosuppressive/immunomodulating 
medication; methotrexate; cyclosporine; oral JAK inhibitors; or 
apremilast) 
Note: Intranasal corticosteroids and inhaled corticosteroids are allowed. 
Eye and ear drops containing corticosteroids are also allowed. 
4 weeks 
Strong or moderate CYP3A4 inhibitors (such as itraconazole), see 
Appendix 1 for a list of prohibited medications in this class. 
4 weeks 
Terbinafine 
4 weeks 
PUVA treatment, UV-B phototherapy (including tanning beds), or 
excimer laser, or tanning booths 
4 weeks 
Topical medication that could affect psoriasis (including corticosteroids, 
retinoids, vitamin D analogues [such as calcipotriol], JAK inhibitors, or 
tar)  
2 weeks 
For subjects consenting to biopsy collection only: Anticoagulant 
medication, such as heparin, LMW heparin, warfarin, or antiplatelet 
agents (except low-dose aspirin ≤ 81 mg which will be allowed). 
Nonsteroidal anti-inflammatory drugs will not be considered antiplatelet 
agents and will be allowed. 
2 weeks 
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Prohibited Medications, Products, And Procedures 
Washout Period Prior 
To First Dose (Day 1)  
Grapefruit 
Note: Consumption of grapefruit must be avoided during the treatment 
period and for at least 1 week after last dose administration. 
1 week 
Abbreviations: COVID-19, Coronavirus Disease 2019; CYP3A4, cytochrome P450 3A; IL, interleukin; JAK, 
Janus kinase; LMW, low molecular weight; PUVA, psoralen-ultraviolet-A; UV, ultraviolet. 
 
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7. 
DISCONTINUATION AND LOST TO FOLLOW-UP 
7.1. 
Discontinuation from Study Treatment 
Medical judgment should be applied to guide whether study treatment discontinuation or careful 
monitoring may be the most appropriate course of action. If it is deemed by the investigator that 
it is in the best interest of the subject to discontinue further study treatment, the medical monitor 
should be contacted as soon as possible for consultation.  
Subjects must be permanently discontinued from study treatment for the following reasons: 
• Pregnancy of a female participant 
• The subject experiences a medical emergency that necessitates permanent 
discontinuation and/or unblinding of the subject’s treatment assignment 
• The subject is unwilling or unable to comply with the protocol 
• At the discretion of the investigator for medical reasons or noncompliance 
• Subject initiates any of the following prohibited medications (Section 6.4.2): 
– 
Therapeutic agent targeting IL-12, IL-17, and/or IL-23 (eg, ustekinumab, 
secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, risankizumab) 
– 
Rituximab or other immune cell depleting agents 
– 
Other marketed or investigational biological agent not listed above 
– 
Live-attenuated vaccine 
Note: Non-live-attenuated vaccines or boosters for COVID-19 (eg, RNA-based 
vaccines, inactivated adenovirus-based vaccines, protein-based vaccines) are allowed 
during the study. The study site should follow local guidelines related to COVID-19. 
– 
Nonbiological investigational product or device 
– 
Intravenous antibiotic treatment 
– 
Systemic treatment that could affect psoriasis (including oral, intravenous, 
intraarticular, intrathecal, or intramuscular corticosteroids; oral retinoids; 
immunosuppressive/immunomodulating medication; methotrexate; cyclosporine; oral 
JAK inhibitors; or apremilast). Intralesional injections are prohibited medications for 
the duration of the study; however, their use does not require discontinuation from the 
study and should be discussed with the medical monitor to determine final subject 
disposition. 
• If the subject experiences a CTCAE Grade ≥2 cytopenia (anemia, leukopenia, 
neutropenia, lymphopenia, and thrombocytopenia; clinically significant or not) as defined 
in Section 8.4.7, for a second time after re-challenge, as detailed in the following 
paragraph. 
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Subjects must at least be temporarily discontinued from study treatment for the following 
reasons: 
• The subject experiences a CTCAE Grade ≥2 cytopenia (anemia, leukopenia, 
neutropenia, lymphopenia, and thrombocytopenia; clinically significant or not) as 
defined in Section 8.4.7. The subject should be followed with periodic testing until 
the laboratory values return to normal range, at which time dosing may be resumed. If 
the same subject develops CTCAE Grade ≥2 cytopenia for a second time after dosing 
is resumed, then the subject will be permanently discontinued from treatment but may 
be continued in the trial and followed until resolution of the adverse event(s). 
• The subject has met study treatment discontinuation criteria for abnormalities 
suggestive of drug induced liver injury (DILI) as described in Section 8.4.8. 
Temporary discontinuation may or may not lead to permanent discontinuation of study treatment 
pending results of further workup and the overall clinical assessment. 
Subjects may be discontinued from study treatment for any of, but not limited to, the following 
reasons: 
• Occurrence of a drug-related SAE (see Section 8.4.2).  
• Occurrence of a severe drug-related AE (see Section 8.4.3).  
• Initiation of a protocol prohibited therapy or procedure (Section 6.4.2) other than 
those for which the subject must be permanently discontinued from study treatment. 
Study procedures should be continued to be evaluated for safety, PK, and other parameters even 
in the event of dosing discontinuation. The medical monitor should be contacted for consultation, 
including if it may be appropriate to exclude any of the planned procedures. In the event a 
decision is made to permanently discontinue dosing and all other interventions, please refer to 
the data to be collected at the ET visit of the schedule of events. 
7.2. 
Discontinuation from Study 
Subjects have the right to withdraw from the study at any time for any reason without penalty. 
The investigator also has the right to withdraw subjects from the study if he or she feels it is in 
the best interest of the subject or if the subject is uncooperative or noncompliant.  
Should a subject decide to withdraw, all efforts will be made to complete and report the 
observations as thoroughly as possible, particularly the examinations outlined in the ET visit. 
The investigator or one of his or her staff members should contact the subject to determine as 
accurately as possible the primary reason for the withdrawal.  
A complete final evaluation at the time of the subject’s withdrawal should be made with an 
explanation of why the subject is withdrawing from the study. If the reason for removal of a 
subject is an AE or an abnormal laboratory test result, the principal specific event or test will be 
recorded. 
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If a subject withdraws from the study, he or she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records. 
Subjects who discontinue the study after the first dose will be asked, if they agree, to come for a 
last assessment (ET visit). Subjects who are discontinued for safety reasons may be asked to 
come for additional follow-up visits, at the investigator’s discretion, after the ET visit to ensure 
appropriate medical care and AEs follow-up. 
Subjects who discontinue after Day 1 dosing will not be replaced.  
Reasons for discontinuation may include the following: 
• The investigator decides that the subject should be withdrawn. If this decision is made 
because of an SAE, the study product is to be discontinued in that subject 
immediately and appropriate measures are to be taken. The investigator will notify 
the sponsor immediately. 
• The subject, for any reason, requires treatment with another therapeutic agent that has 
been demonstrated to be effective for treatment of the study indication.  
• The subject fails to comply with other protocol requirements. 
• The subject is unable to continue visits or the study site is closed due to COVID-19 
pandemic restrictions. 
• The subject is withdrawn for any medical condition or circumstance that exposes the 
subject to substantial risk and/or does not allow the subject to adhere to the 
requirements of the protocol. 
• The subject is lost to follow-up. In this case, a reasonable attempt to contact the 
subject and ascertain his or her status must be made, and these attempts must be 
documented. 
• Other: the subject may withdraw from the study for any other reason, including 
withdrawal of consent. 
• Study termination by the sponsor or regulatory authorities (refer to Section 7.4). 
7.3. 
Lost to Follow-Up 
A subject will be considered lost to follow-up if he or she fails to return for scheduled visits and 
is unable to be contacted by the study site staff.  
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit (unless this is required by the COVID-19 situation and virtual visits are scheduled instead): 
• The site will attempt to contact the subject and reschedule the missed visit. The site 
will then counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain if the subject wishes to or should continue in the study. 
• Before a subject is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the subject (where possible, three telephone calls 
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and, if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the subject’s 
medical record or study file. 
• If all attempts to contact the subject fail he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
7.4. 
Study Termination 
The Sponsor has the right to terminate the study for any reason and at any time. Reasons for 
terminating the study may include, but are not limited to, the incidence or severity of TEAE in 
this or other studies indicating a potential health risk to participants. In this case, all subjects will 
be discontinued from the study. The investigator will immediately, on discontinuance of the 
study by the sponsor, in its entirety or at a clinical study site, inform both the subjects and the 
IRB/REB of the discontinuance, provide them with the reasons for the discontinuance and advise 
them in writing of any potential risks to the health of subjects or other persons. The study can 
also be terminated by IRB and/or regulatory agency for any unforeseen reasons. 
 
 
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8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. 
Efficacy Assessments 
Clinical evaluations of plaque psoriasis will be performed by an experienced and qualified 
dermatologist (board certified or equivalent) or other suitably qualified and experienced 
designee. To assure consistency and reduce variability, the same assessor should perform all 
assessments on a given subject whenever possible. 
8.1.1. 
Psoriasis Area and Severity Index 
The PASI will be evaluated at the visits specified in Table 1. This index quantifies the severity of 
a subject’s psoriasis based on both lesion severity and the percentage of BSA affected.15 The 
PASI is a composite score ranging from 0 to 72 that that takes into account the degree of 
erythema, induration/infiltration, and desquamation (each scored from 0 to 4 separately) for each 
of four body regions, with adjustments for the percentage of BSA involved for each body region 
and for the proportion of the body region to the whole body. Refer to Appendix 2 for a complete 
description of this scale. To be eligible for this study, subjects must have a PASI score ≥ 12 at 
screening and Day 1 visit. 
8.1.2. 
Physician’s Global Assessment 
The PGA of disease severity will be assessed at the visits specified in Table 1. The PGA is a 
global assessment of the current state of the disease. It is a 5-point morphological assessment of 
overall disease severity. A detailed description of PGA16 scores is provided in Table 5. To be 
eligible for this study, subjects must have a PGA score ≥ 3 at screening and Day 1 visit. 
Table 5: 
Physician’s Global Assessment 
Score 
Grade 
Description 
0 
Clear 
No signs of psoriasis; post-inflammatory hyperpigmentation may be present 
1 
Almost clear 
No thickening; normal to pink coloration; no to minimal focal scaling 
2 
Mild 
Just detectable to mild thickening; pink to light red coloration; 
predominantly fine scaling 
3 
Moderate 
Clearly distinguishable to moderate thickening; dull to bright red; clearly 
distinguishable to moderate erythema; moderate scaling 
4 
Severe 
Severe thickening with hard edges; bright to deep dark red coloration; 
severe/coarse scaling covering almost all or all lesions 
8.1.3. 
 
 
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. 
8.1.4. 
 
 
 
 
 
 
. 
8.1.5. 
 
 
 
 
 
 
 
8.2. 
Quality-of-Life Assessments/Subject Reported Outcomes 
8.2.1. 
Dermatology Life Quality Index Questionnaire  
The DLQI will be assessed at the visits specified in Table 1. It is a simple 10-question validated 
questionnaire that has been used in more than 40 different skin conditions.21 Its use has been 
described in more than 1,000 publications, including many multinational studies. The DLQI is 
the most frequently used instrument in studies of randomized controlled studies in dermatology. 
The questionnaire is provided in Appendix 5.   
8.3. 
Safety and Other Assessments 
8.3.1. 
Vital Signs 
The following vital signs will be recorded at the visits specified in Table 1 with the subject in a 
seated position, after having sat calmly for at least 5 minutes: systolic and diastolic blood 
pressure (mmHg), pulse (bpm), and body temperature (°C).  
Weight (kg) will be recorded at the visits specified in Table 1. Height (cm) will only be recorded 
once at the screening visit. 
Any abnormal finding related to vital signs that the investigator considers to be clinically 
significant must be recorded as an AE starting after dosing on Day 1.  
8.3.2. 
Physical Examination 
The following sites/systems will at least be included in the complete physical examination, 
which will be performed at the visits specified in Table 1:  
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• General appearance 
• Dermatological (except plaque psoriasis) 
• Head, eyes, ears, nose, throat 
• Respiratory 
• Cardiovascular 
• Abdominal 
• Neurological 
• Musculoskeletal 
• Lymphatic 
Information for all physical examinations must be included in the source document. Any 
significant change will be reported as an AE in the source document and eCRF starting after 
dosing on Day 1.  
8.3.3. 
Targeted Physical Examination 
The following sites/systems will at least be included in the targeted physical examination that 
will be performed at the visits specified in Table 1:  
• General appearance 
• Dermatological (except plaque psoriasis) 
• Respiratory 
• Cardiovascular 
• Abdominal 
If deemed appropriate by the investigator based on the subject’s condition, a complete physical 
examination as described in Section 8.3.2 can be performed instead of a targeted examination. 
Information for all physical examinations must be included in the source document. Any 
significant change will be reported as an AE in the source document and eCRF starting after 
dosing on Day 1.  
8.3.4. 
Clinical Laboratory Tests 
Laboratory tests will be performed at the visits specified in Table 1. The specific tests in these 
panels are listed in Table 6. 
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Table 6: 
Clinical Laboratory Testing  
Laboratory Testing 
Tests Included 
Hematology 
aPTT, HCT, Hgb, INR, MCH, MCHC, MCV, MPV, PLT, PT, RBC, WBC, 
and differentials (neutrophils, lymphocytes, monocytes, eosinophils, and 
basophils relative and absolute) 
Biochemistry 
Albumin, alkaline phosphatase, ALT, AST, calcium, CPK, creatinine 
(enzymatic), GGT, glucose random, potassium, sodium, total bilirubin, direct 
bilirubin if total bilirubin > ULN, urea (BUN), uric acid 
Fasting lipids 
Cholesterol (total, LDL, and HDL), triglycerides (all fasting) 
Urinalysis 
Color, clarity, pH, specific gravity, bilirubin, glucose, ketones, leukocytes, 
nitrite, blood, protein, urobilinogen 
Microscopic analysis (as required) 
Urine pregnancy test 
(conducted at the 
investigator site) 
For WOCBP (at each visit, except screening) 
Laboratory tests 
required at screening 
only 
FSH levels for female subjects who have had a cessation of menses for at 
least 12 months prior to the screening visit without an alternative medical 
cause 
β-hCG for WOCBP 
Tuberculosis test (QuantiFERON-TB Gold) 
• 
Note: A T-Spot.TB test (TBT) may be used as an alternative to the 
QuantiFERON-TB Gold test as per Exclusion Criterion 17. If the 
TBT is used, the QuantiFERON-TB Gold test should not be 
performed. 
Serology (HBV [HBsAg, anti-HBc], HCV, HIV)  
Abbreviations: ALT, alanine aminotransferase; anti-HBc, antibody to hepatitis B core antigen; aPTT, activated 
partial thromboplastin time; AST, aspartate aminotransferase; β-hCG, β-human chorionic gonadotropin; BUN, blood 
urea nitrogen; CPK, creatine phosphokinase; FSH, follicle-stimulating hormone; GGT, 
gamma--glutamyl-transferase; HBsAg, hepatitis B surface antigens; HBV, hepatitis B virus; HCT, hematocrit; HCV, 
hepatitis C virus; Hgb, hemoglobin; HIV, human immunodeficiency virus; INR, international normalized ratio; 
LDH, lactate dehydrogenase; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin 
concentration; MCV, mean corpuscular volume; MPV, mean platelet volume; PLT, platelets; PT, prothrombin time; 
RBC, red blood cell (count); ULN, upper limit of normal; WBC, white blood cell (count); WOCBP, women of 
childbearing potential. 
 
In case of a screening laboratory value abnormality, the test can be repeated once within the 
original screening time window, if the investigator believes there is a reasonable possibility that 
the subject would be eligible if re-tested. The QuantiFERON-TB test can only be repeated once 
if the result is indeterminate; tests with positive or negative results will not be repeated. The TBT 
may be used as an alternative to the QuantiFERON-TB test per Exclusion Criterion 17. The TBT 
may be repeated once only if the result is borderline (equivocal); tests with positive or negative 
results will not be repeated. 
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After the subject’s first dose on Day 1, any clinically significant value will be reported as an AE. 
Any CTCAE Grade ≥ 2 cytopenia (anemia, leukopenia, neutropenia, lymphopenia, or 
thrombocytopenia; clinically significant or not) or CTCAE Grade ≥ 3 elevation of CPK 
(clinically significant or not) will be reported as an AE and AESI (Section 8.4.7).  If a subject 
experiences a CTCAE Grade ≥2 cytopenia (anemia, leukopenia, neutropenia, lymphopenia, and 
thrombocytopenia; clinically significant or not) as defined in Section 8.4.7, dosing will be 
interrupted, and the subject followed with periodic testing until the laboratory values return to 
normal range. If the same subject develops a CTCAE Grade ≥2 cytopenia for a second time after 
dosing is resumed, then the subject will be permanently discontinued from treatment, but may be 
continued in the trial and followed until resolution of the adverse event(s). 
8.3.4.1. 
Use of Local Laboratories 
All protocol-specified laboratory tests (See Table 6) should be performed via the central 
laboratory. All attempts should be made to perform the laboratory assessments at the study site, 
via the central laboratory. In situations where the laboratory tests cannot be performed at the 
study site due to extenuating circumstances, such as quarantine or immobilization, the protocol-
specified laboratory examinations may be conducted through a local laboratory. If the TBT is 
used as an alternative to the QuantiFERON-TB Gold test as per Exclusion Criterion 17, it may 
be performed via a local laboratory. 
Use of local laboratories for any purpose beyond collection of protocol-specific laboratory tests 
that cannot be performed at central laboratory due to extenuating circumstances should be 
discussed with the medical monitor. Results from local laboratories will be recorded on the 
appropriate eCRF. 
Follow-up safety monitoring will be conducted at the investigator’s discretion. Results 
determined by the investigator to be SAEs or AESI, should be reported to the sponsor following 
the procedures described in Section 8.4.6, Section 8.4.7, and the Study Reference Manual, as 
applicable. 
8.3.5. 
Electrocardiogram  
Twelve-lead ECGs will be performed as a safety assessment at the visits specified in Table 1. 
Any clinically significant value will be reported as an AE starting on Day 1.  
8.3.6. 
Plasma Concentration of NDI-034858 
Blood samples will be collected to measure plasma levels of NDI-034858 as follows: 
• On Day 1 prior to dosing and 1 hour (± 5 min) postdosing; 
• At Week 4 prior to dosing, 1 hour (± 5 min) postdosing, and 4 hours (± 10 min) 
postdosing; 
• At Week 8 prior to dosing; 
• At Week 12 anytime (no study treatment administration at this visit). 
• At ET visit anytime (if ET visit is planned before Week 12 visit).  
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The actual date and time of each blood sample collection will be recorded. Details about the 
collection, processing, handling, storage, and shipping of plasma samples will be provided in the 
laboratory manual. 
8.3.7. 
 
 
 
 
.  
8.3.8. 
 
 
  
 
 
. 
8.3.9. 
 
 
 
 
 
 
 
 
 
 
. 
8.3.10. 
 
 
 
. 
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8.3.11. 
Medical Photography 
Medical photographs will be performed in a subset of subjects who consent to the procedure at 
the visits specified in Table 1.  
Photographs will be identified as follows: study number, subject number, visit name, and date. 
Photographs will be uploaded and stored on a secured clinical website and will be transmitted to 
the sponsor for review. Additional information will be provided in the study reference manual. 
8.3.11.1. Medical Photography - Biopsies 
Investigator-selected target plaque areas will be biopsied. These target areas should be 
documented in the subject record and EDC, and the same targeted plaque areas should be 
followed throughout the study. All biopsied areas will be photographed prior to biopsy. 
Care will be taken to use the same camera, the same magnification, and the same settings for 
each photograph at each visit in order to obtain comparable pictures. Medical photographs will 
be taken using a blue background. 
8.3.11.2. Medical Photography- Full Body Front and Back 
For full body photographs, all study photographs will be captured using the equipment, supplies, 
and guidelines provided by the sponsor or sponsors vendor. 
Medical photographs, full body front and back, will be performed at selected study sites, in a 
subset of subjects who give written informed consent to the procedure, at the visits specified in 
Table 1. The full body photographs consist of four captures which include the upper 
posterior/anterior from the neck down and lower anterior/posterior from the toes up.  
8.4. 
Adverse Events and Serious Adverse Events 
8.4.1. 
Definition of Adverse Event  
An AE is any untoward medical occurrence in a subject administered a pharmaceutical product 
and that 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 study product, whether or not considered related 
to the study product. 
8.4.2. 
Definition of Serious Adverse Event  
A SAE is any untoward medical experience occurring at any dose that results in any of the 
following consequences: 
• Results in death 
• Is life-threatening 
• Requires in-patient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
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• Is a congenital anomaly/birth defect 
• Is an important medical event that may not be immediately life-threatening or result 
in death or hospitalisation but may jeopardize the subject or may require intervention 
to prevent one of the other outcomes listed above (according to medical judgment of 
the investigator). 
Note: The term “life-threatening” in the definition of “serious” refers to an event in which the 
subject was at risk of death at the time of the event; it does not refer to an event that 
hypothetically might have caused death if it were more severe. Medical and scientific judgment 
should be exercised in deciding whether expedited reporting is appropriate in other situations, 
such as important medical events that may not be immediately -life-threatening or result in death 
or hospitalization but may jeopardize the subject or may require intervention to prevent one of 
the other outcomes listed in the definition above. These should also usually be considered 
serious. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasia, convulsions that do not result in hospitalization, or development 
of drug dependency or drug abuse. 
Scheduled hospitalizations or elective surgical procedures will not be considered SAEs. 
Prolongation of a scheduled hospitalization can be considered an SAE.  
8.4.3. 
Classification of an Adverse Event 
8.4.3.1. 
Relationship to Study Treatment 
The investigator will assess causal relationship between each reported AE or SAE, and the 
experimental treatment. The investigator should consider the subject’s medical history, most 
recent physical examination findings, and concomitant medications.  
The following definitions will be used to determine the causality of an AE or SAE:  
• Not related: Temporal relationship of the onset of the AE or SAE, relative to the 
experimental treatment, is not reasonable, or another cause can explain the occurrence 
of the AE. 
• Related: Temporal relationship of the onset of the AE or SAE, relative to the 
experimental treatment, is reasonable, follows a known response pattern to the 
treatment, and an alternative cause is unlikely. 
8.4.3.2. 
Adverse Event Severity 
The severity of an AE or SAE is an estimate of the relative intensity of the event made by the 
investigator based on his or her clinical experience and familiarity with the literature. The 
following definitions from the National Cancer Institute (NCI) CTCAE, Version 5.0, published 
27-Nov-2017 are to be used to rate the severity of an AE or SAE: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
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• Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADL)*. 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
selfcare ADL**. 
• Grade 4: Life-threatening consequences; urgent intervention indicated. 
• Grade 5: Death related to AE. 
Note: A Semi-colon indicates ‘or’ within the description of the grade.  
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc. 
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
Changes in severity should be documented in the medical record to allow assessment of the 
duration of the event at each level of severity. Adverse events characterized as intermittent 
require documentation of the start and stop of each incidence.  
When changes in the severity of an AE occur more frequently than once a day, the maximum 
severity for the experience that day should be noted. If the severity category changes over several 
days, then those changes should be recorded separately (with distinct onset dates). 
8.4.4. 
Time Period and Frequency for Event Assessment and Follow-Up 
The occurrence of an AE or SAE may come to the attention of study personnel during study 
visits and interviews of a study subject presenting for medical care, or upon review by a study 
monitor. 
All AEs, including local and systemic reactions, will be captured on the appropriate eCRF. 
Information to be collected includes event description, date of onset, clinician’s assessment of 
severity, relationship to study product (assessed only by those with the training and authority to 
make a diagnosis), and date of resolution/stabilization of the event. All AEs occurring while on 
study must be documented appropriately regardless of relationship.  
Study site personnel will note the occurrence and nature of each subject’s medical condition(s) 
present prior to dosing on Day 1 in the appropriate section of the source document and eCRF. 
Starting at dosing on Day 1, site personnel will note any change in the condition(s) and the 
occurrence and nature of any AE.  
Any medical condition that is present prior to dosing on Day 1 will be considered as part of 
medical history and not reported as an AE. However, if the study subject’s condition deteriorates 
after dosing on Day 1, it will be recorded as an AE. 
Should a subject experience an AE at any time after dosing on Day 1 until the end of 
participation in the study, the event will be recorded as an AE in the source document and eCRF. 
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Of note, any SAE related to the study participation (eg, screening procedure) will be recorded in 
the source document and eCRF from dosing on Day 1 until the end of participation in the study. 
The investigator is responsible for appropriate medical care of subjects during the study. The 
investigator also remains responsible for following through with an appropriate health care 
option for all AEs that are ongoing at the end of the study. If an AE is ongoing at the end of 
study, the follow-up duration is left to the discretion of the investigator. Follow-up frequency 
will be performed at the discretion of the investigator. However, in case of an SAE, the subject 
should be followed until the event is resolved or stabilized as per the investigator’s judgment. 
8.4.5. 
Adverse Event Reporting 
Investigators are responsible for monitoring the safety of subjects who are participating in this 
study and for alerting the sponsor to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the subject.  
8.4.6. 
Serious Adverse Event Reporting 
 All SAEs, related to the experimental treatment or not, occurring during the study (from dosing 
on Day 1 to last study visit) must be reported on an SAE form to the sponsor-delegated vendor 
(see below contact information) within 24 hours of the knowledge of the occurrence (this refers 
to any AE that meets one or more of the aforementioned serious criteria). When applicable, 
follow-up information should be reported to the sponsor-delegated vendor in the same manner as 
the original SAE report. 
The SAE reporting period ends at the end of the follow-up period. 
Reporting should be done by sending the completed SAE form to the following e-mail address 
(faxing can also be done as a second option in case e-mailing is not possible). 
Safety Contact Information: Innovaderm Drug Safety unit  
E-mail: drugsafety@innovaderm.com 
Fax: (514) 221-4199 
Further to the determination of expedited criteria, the sponsor and delegate will manage the 
submission of individual case safety report to concerned regulatory agencies in accordance with 
local laws and regulations. 
8.4.7. 
Adverse Events of Special Interest 
The following are AESI:  
• CTCAE Grade ≥ 2 cytopenia (anemia, leukopenia, neutropenia, lymphopenia, or 
thrombocytopenia; clinically significant or not) defined by the following ranges:  
− Hemoglobin < 10.0 g/dL (< 100.0 g/L). 
− White blood cell count < 3.0 x 109/L (< 3000/mm3). 
− Absolute neutrophil count of < 1.5 x 109/L (< 1500/mm3). 
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− Absolute lymphocyte count of < 0.8 x 109/L (< 800/mm3). 
− Platelet count < 75 x 109/L (< 75000/mm3). 
• CTCAE Grade ≥ 3 elevation of CPK (clinically significant or not) defined as CPK > 
5x ULN  
• Major adverse cardiovascular events, defined as cardiovascular death, nonfatal 
myocardial infarction, and nonfatal stroke 
• Thromboembolic events, defined as pulmonary embolism, deep vein thrombosis, and 
other venous and arterial thromboembolic events (eg, noncardiac, non-neurologic, 
fatal and nonfatal) 
• Gastrointestinal perforation 
• Malignancies 
– 
All malignancies 
– 
Non-melanoma skin cancer (NMSC) 
– 
Malignancy excluding NMSC 
– 
Lymphoma 
• Infections 
– 
All infections 
– 
Serious infection 
– 
Opportunistic infection, excluding tuberculosis and herpes zoster 
– 
Herpes zoster 
– 
Active tuberculosis 
• Adverse events of abnormal liver function tests 
• Adverse events of renal dysfunction 
Adverse events of special interest should be reported beginning  on Day 1 after the first dose of 
study drug  using the procedures detailed in Section 8.4.6. If an AESI does not meet any 
seriousness criteria, it must still be reported according to the SAEs reporting procedures for 
initial and follow-up reporting, but an AESI form would be used. 
As per Section 7.1, if a subject experiences a CTCAE Grade ≥2 cytopenia (anemia, leukopenia, 
neutropenia, lymphopenia, and thrombocytopenia; clinically significant or not) as defined in 
Section 8.4.7 , dosing will be interrupted, and the subject followed with periodic testing until the 
laboratory values return to normal range. If the same subject develops a CTCAE Grade ≥2 
cytopenia for a second time after dosing is resumed, then the subject will be permanently 
discontinued from treatment, but may be continued in the trial, and followed until resolution of 
the adverse events. 
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Immediate Reporting of AESI  
1. Adverse events of special interest should be reported beginning on Day 1 after the first 
dose of study drug.  The study site must formally notify the sponsor-delegated vendor 
within 24 hours of knowledge of the occurrence.  
2. Even if an AESI does not meet any seriousness criteria, it must still follow the SAEs 
reporting procedures for initial and follow-up reporting (Section 8.4.6); however, an 
AESI form will be used. 
3. All AESIs must be reported to the sponsor-delegated vendor within 24 hours of 
knowledge of the occurrence regardless of the following: 
4.  Whether or not the subject has undergone study-related procedures 
5. The severity of the event 
6. The relationship of the event to study drug 
7. Refer to the Study Reference Manual’s Official Study Contact List for complete contact 
information to report initial or follow-up information on an AESI. 
8.4.8. 
Potential Drug Induced Liver Injury 
Alanine aminotransferase or AST values ≥ 3 times the ULN will trigger the following actions 
and evaluations:  
• The medical monitor should be contacted immediately; 
• Liver tests including ALT, AST, total bilirubin, and alkaline phosphatase will be 
repeated from the original blood sample as soon as possible, and no longer that 
72 hours after originally reported. 
The following combination of signs, symptoms, or laboratory values (based on the original 
values, not the repeat), require at least temporary discontinuation of the study medication while 
workup is ongoing: 
• ALT or AST ≥ 3 times the ULN and total bilirubin > 2 times the ULN in the presence 
of normal alkaline phosphatase; 
• ALT or AST ≥ 8 times the ULN, regardless of other parameters; 
• ALT or AST > 3 times the ULN with the appearance of fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
ALT or AST values ≥ 3 times the ULN but < 8 times the ULN without total bilirubin > 2 times 
the ULN or the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, 
fever, rash, and/or eosinophilia (>5%) do not require discontinuation of study treatment while 
workup is ongoing. Nonetheless, a subject may have dosing held based on investigator’s medical 
judgement. Temporary discontinuation of study treatment may or may not lead to permanent 
discontinuation pending results of further workup and the overall clinical assessments. The 
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frequency of monitoring liver tests or relevant laboratory tests will be decided as part of the 
consultation between the investigator and medical monitor. 
The medical monitor will work with the investigator to evaluate other possible causes of the 
observed liver test abnormalities. These other possible causes could include hepatitis (viral, 
alcoholic, or autoimmune); hepatobiliary disorders; nonalcoholic steatohepatitis; cardiovascular 
causes; and other concomitant treatments (https://www.fda.gov/regulatory-information/search-
fda-guidance-documents/drug-induced-liver-injury-premarketing-clinical-evaluation). 
8.4.9. 
Pregnancy Reporting 
If a female subject becomes pregnant after dosing on Day 1 during the study and up to 4 weeks 
after the end of the study, or if a female partner of a male subject becomes pregnant after male 
subject dosing on Day 1 during the study and up to 12 weeks after the end of the study, the 
subject should inform the study site as soon as possible. Upon confirmation of the pregnancy, the 
female subject will be permanently discontinued from the study treatment, if this occurs before 
the end of dosing period. The investigator must complete a study specific pregnancy form upon 
confirmation of a pregnancy and report it to the sponsor-delegated vendor within 24 hours of 
confirmation of the pregnancy (contact information to be used is the same as for SAE reporting). 
All cases of pregnancy will be reported to the sponsor-delegated vendor in a timely manner using 
the Pregnancy Form. Pregnancy is not itself an AE or SAE; however, maternal/fetal 
complications or abnormalities will be recorded as AEs or SAEs, as appropriate. The investigator 
will follow the pregnancy until completion or until pregnancy termination and, in the case of a 
live-born offspring, to 1 month of age in that infant. Congenital abnormalities and birth defects 
in the offspring of male or female subjects should be reported as an SAE if conception occurred 
during the study drug period, or within 5 times the half-life or 12 weeks from their last dose of 
study drug, whichever is longer. The investigator will notify the pharmacovigilance unit of the 
outcome as a follow-up to the initial pregnancy form. All pregnancies should be reported to the 
sponsor and, when applicable, to the ethics committee. 
8.4.10. 
Overdose 
Study product overdose is any accidental or intentional use of study product in an amount higher 
than the dose indicated per protocol for a given subject. Study product compliance (see 
Section 6.3.2) should be reviewed to detect potential instances of overdose (intentional or 
accidental). 
Any study product overdose during the study should be recorded on the source document and 
eCRF. In the event of overdose, the subject should be closely monitored for any potential AEs. 
All AEs associated with an overdose should be entered on the Adverse Event eCRF and reported 
using the procedures detailed in Section 8.4.6, Serious Adverse Events Reporting, even if the 
events do not meet seriousness criteria. If the AE associated with an overdose does not meet 
seriousness criteria, it must still be reported using the SAEs reporting procedures, but an 
overdose form would be used. The excess quantity and duration of the overdose should be 
recorded. 
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9. 
STATISTICAL CONSIDERATIONS  
9.1. 
Sample Size Determination 
The sample size determination is based on testing equality of two independent response rates 
using a 2-sided test with significance level of alpha = 0.05 and power 85%. The formula used for 
the calculation is the same as used in the nQuery® (ie, normal approximation with Fleiss’ 
formula and continuity correction). 
Assuming the placebo response rate at end of Week 12 is 10% (proportion of subjects achieving 
PASI-75), at least one of the NDI-034858 dose treatment groups will have a response rate at 
least 40%, and after adjustment of 15% dropout rate, a total of 250 subjects (50 per treatment 
group) will be randomized in the study.  
9.2. 
Populations for Analyses 
Efficacy will be evaluated on the basis of mITT analysis set. A supportive analysis will also be 
conducted on the PP analysis set. 
Intent-to-treat (ITT) analysis set: This analysis set will include all subjects who were 
randomized. All subjects will be analyzed according to the treatment group to which they were 
randomized.  
Modified intent-to-treat (mITT) analysis set: This analysis set will include all subjects who were 
randomized and received at least one dose of study treatment. All subjects will be analyzed 
according to the treatment group to which they were randomized. The mITT analysis set will be 
used as the primary analysis population for efficacy. 
Per-protocol (PP) analysis set: This analysis set will include all subjects who were randomized, 
who received at least one dose of study product, and who provided evaluable data for the 
primary endpoint with no major protocol deviations affecting the efficacy evaluations. All 
subjects will be analyzed according to the treatment group that they actually received. 
Safety analysis set: This analysis set will include all subjects who received at least one dose of 
the study product. All subjects will be analyzed according to the treatment  they received. 
Pharmacokinetic (PK) analysis set: This analysis set will include all subjects who received at 
least one dose of NDI-034858 and have evaluable plasma concentration data. 
. 
9.3. 
Statistical Analyses 
9.3.1. 
General Approach 
Categorical variables will be presented in tables as frequencies and percentages. Continuous 
variables will be summarized in tables and will include the number of subjects, mean, SD, 
median, minimum, and maximum.  
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Further details regarding the efficacy and safety variable definitions, analyses strategy, statistical 
justification, and techniques for handling missing values (if applicable) will be detailed in a 
separate SAP that will be prepared before the database is locked and any analyses are 
undertaken. Any deviation(s) from the SAP will be described and justified in the final Clinical 
Study Report, as appropriate. 
All statistical tests will be two-sided and will be performed with a significant level of 0.05, 
unless otherwise specified in the SAP. To account for the multiplicity testing in the primary 
endpoint analysis, each active treatment group will be compared to the placebo group using a 
hierarchical testing procedure, starting with the highest dose group and ending with the lowest 
dose group (30-mg NDI-034858, 15-mg NDI-034858, 5-mg NDI-034858, and 2-mg NDI-
034858, in order). No adjustment to alpha will be made to account for multiple testing between 
treatment groups for the secondary 
 efficacy endpoints.  
9.3.2. 
Efficacy Analyses 
The primary endpoint can be translated as a responder analysis, where a subject will be classified 
as responder if he or she achieves PASI-75 at Week 12. The comparison between groups for the 
primary endpoint will be done using a CMH, with prior treatment with biologics included as a 
stratification factor. The primary efficacy analysis will be performed on the mITT analysis set, 
while the PP analysis set will be used as a sensitivity analysis. 
The secondary endpoints involving proportions of subjects will be analyzed using the same 
approach (CMH test) as described for the primary efficacy analysis, at each time point and based 
on the mITT analysis. 
The continuous secondary endpoints involving absolute change from baseline will be analyzed 
using an MMRM based on the mITT analysis set only. The model will include treatment, visit, 
treatment by-visit interaction, and prior treatment with biologics as fixed effects, and baseline 
score as a covariate. 
9.3.3. 
Safety Analyses 
All safety analyses will be conducted using the safety analysis set. No inferential statistics will 
be performed on safety variables. Adverse events and SAEs will be presented and tabulated 
according to MedDRA classification by treatment group. Descriptions of AEs will include the 
start date, the stop date (if it resolved), the severity and seriousness of the AE, the relationship of 
the AE to study product, action taken with respect to the study product and the outcome. 
Reported AEs will be summarized by the number of subjects reporting the events, as well as by 
system organ class, preferred term, reported verbatim severity, seriousness, and investigator’s 
assessment of the relationship to study product. For the summary of AEs by severity, each 
subject will be counted only once within a system organ class or a preferred term by using the 
AEs with the highest intensity within each category for each analysis. For the summary of AEs 
by relationship to study product, each subject will be counted only once within a system organ 
class or a preferred term by using the AEs with the greatest reported relationship within each 
category. For the summary of AEs by relationship to study product and severity, each subject 
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will be counted only once within a system organ class or a preferred term by using (1) the 
greatest reported relationship followed by (2) the highest reported intensity. 
All information pertaining to AEs noted during the study will be listed by treatment group, 
subject, detailing verbatim, system organ class, preferred term, start date, stop date, intensity, 
outcome, action taken with respect to study product, and relationship to study product. The AE 
onset will also be shown relative (in number of days) to the day of study product administration. 
Serious adverse events will be tabulated by treatment group, relationship to the test article, and a 
reference to the occurrence of the SAEs to the relative day of dosing. Similar listings will be 
provided for the SAEs and AEs leading to the discontinuation from the study. 
Results from vital signs, laboratory analyses, and ECGs will be tabulated by treatment and visit 
using descriptive statistics. The observed value at each visit, as well as the change from baseline 
will be presented. Shift tables describing shifts to out-of-normal range will be provided for 
clinical laboratory results, and normal to abnormal shift tables may be provided for vital signs. 
Concomitant medications will be coded with the WHO-DD and listed by subject. Summary of 
medication classes will also be tabulated. 
9.3.4. 
Pharmacokinetic Analyses 
Concentration data will be listed per subject and summarized descriptively per dose.  
9.3.5. 
 
. 
9.3.6. 
Other Analyses 
Descriptive summaries of subject disposition and baseline characteristics (including 
demographic data and prior concomitant therapy) will be presented by treatment group. In 
addition, a list of subjects who discontinued from the study along with discontinuation reason 
will be provided. 
Protocol deviations will be summarized by treatment and category. 
9.3.7. 
Planned Interim Analyses 
No interim analysis is planned in this study. 
 
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10. 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
10.1. 
Local Regulations/Declaration of Helsinki 
This study will be conducted in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki and that are consistent with ICH Tripartite Guideline for GCP and 
the applicable laws and regulations of the country in which the research is conducted, whichever 
affords the greater protection to the individual. 
10.2. 
Ethical Review  
It is the understanding of the sponsor that this protocol (and any amendments) as well as 
appropriate consent procedures, will be reviewed and approved by an IRB/REB. This board must 
operate in accordance with the current federal regulations. For sites with a local ethics 
committee, a letter or certification of approval will be sent by the investigator to the sponsor (or 
CRO) before initiation of the study and whenever subsequent modifications to the protocol are 
made. 
10.3. 
Informed Consent Process 
An ICF describing in detail the study treatment, study procedures, and risks will be given to the 
subject, along with an assent form when required. 
It is the responsibility of the investigator, or a person designated by the investigator (if 
acceptable by local regulation), to obtain written informed consent from each i participant in this 
study, after adequate explanation of the aims, methods, objectives, and potential hazards of the 
study. 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
the study and continues throughout the individual’s study participation. Consent forms will be 
IRB/REB approved, and the subject will be asked to read and review the document. The 
investigator will explain the research study to the subject and answer any questions that may 
arise. A verbal explanation will be provided in terms suited to the subject’s comprehension of the 
purposes, procedures, and potential risks of the study and of his or her rights as a research 
subject. Subjects will have the opportunity to carefully review the written consent form and ask 
questions prior to signing. The subjects should have the opportunity to discuss the study with 
their family or surrogates or think about it prior to agreeing to participate. 
The subject will sign the informed consent document prior to any procedures being done 
specifically for the study. Subjects must be informed that participation is voluntary and that they 
may withdraw from the study at any time for any reason, without prejudice. A copy of the signed 
informed consent document will be given to the subjects for their records. The informed consent 
process will be conducted and documented in the source document (including the date), and the 
form signed before the subject undergoes any study-specific procedures. 
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The rights and welfare of the subjects will be protected by emphasizing to them that the quality 
of their medical care will not be adversely affected if they decline to participate in this study. 
If new safety information results in significant changes in the risk/benefit assessment, or if any 
new information becomes available that may affect the willingness of a subject to continue to 
participate, the consent form should, if necessary, be reviewed and updated by the IRB/REB. All 
subjects (including those already being treated) should be informed of the new information, 
given a copy of the revised form, and asked to give their consent to continue in the study. 
10.4. 
Study Discontinuation and Closure 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification documenting the reason for study suspension or 
termination will be provided by the suspending or terminating party to study subjects, 
investigators, the sponsor, and regulatory authorities. If the study is prematurely terminated or 
suspended, the principal investigators will promptly inform study subjects and the IRB/REB and 
will provide the reason(s) for the termination or suspension. Study subjects will be contacted, as 
applicable, and be informed of changes to the study visit schedule. 
Circumstances that may warrant termination or suspension of the study include, but are not 
limited to the following: 
• Determination of unexpected, significant, or unacceptable risk to subjects 
• Insufficient compliance with protocol requirements 
• Data that are not sufficiently complete or evaluable 
• Scientific or corporate reasons 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed and satisfy the sponsor, IRB/REB, Health Canada, and/or FDA. 
10.5. 
Confidentiality and Privacy  
Subject confidentiality and privacy are strictly held in trust by the participating investigators, 
their staff, and the sponsor and their interventions. Confidentiality is extended to cover testing of 
biological samples in addition to the clinical information relating to subjects. Therefore, the 
study protocol, documentation, data, and all other information generated will be held in strict 
confidence. 
The investigator must assure that the subjects’ anonymity will be maintained, and that subjects’ 
identities are protected from unauthorized parties. On case report forms or other documents 
submitted to the sponsor, subjects should not be identified by their names, but by an 
identification code. The investigator should keep a subject log relating codes with the names of 
subjects. The investigator should maintain in strict confidence documents not for submission to 
Nimbus Lakshmi, Inc. (eg, subjects’ written consent forms). 
All research activities will be conducted in a setting as private as possible. 
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The study monitor, other authorized representatives of the sponsor, and representatives of the 
IRB, regulatory agencies, or pharmaceutical company supplying study product may inspect all 
documents and records required to be maintained by the investigator, including but not limited 
to, medical records (office, clinic, or hospital) and pharmacy records for the subjects in this 
study. The clinical study site will permit access to such records. 
The study subject’s contact information will be securely stored at each clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure 
location for as long a period as dictated by the applicable legal or regulatory requirements, the 
reviewing IRB, institutional policies, or sponsor requirements. 
10.6. 
Clinical Monitoring 
Clinical site monitoring will be conducted to ensure that the rights and well-being of study 
subjects are protected; that the reported study data are accurate, complete, and verifiable; and 
that the conduct of the study is following the currently approved protocol/amendment(s), ICH 
GCP guidelines, and with applicable regulatory requirement(s). Details of clinical site 
monitoring will be documented in a Monitoring Plan. 
Centralized monitoring, which consists of remote review of accumulating data from all sites, will 
be performed as detailed in the Centralized Monitoring Plan. 
10.7. 
Quality Assurance and Quality Control 
Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation, and completion. 
Quality control (QC) procedures will be implemented beginning with the data entry system, and 
data QC checks, which will be run on the database, will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution. 
During the study, the sponsor or its representative will conduct monitoring visits at regular 
intervals. The monitoring visits will be conducted to ensure protocol adherence, quality of data, 
accuracy of entries on the eCRFs, study product accountability, compliance with regulatory 
requirements, and continued adequacy of the study site and its facilities. 
The site may be audited, monitored, or inspected by a quality assurance officer named by the 
sponsor, by the REB or IRB, and/or by the regulatory authorities. The investigator will be 
expected to cooperate with any audit and provide assistance and documentation (including 
source data) as requested. The study site will provide direct access to all study-related sites, 
source data/documents, and reports for the purpose of monitoring and auditing by the sponsor 
and inspection by local and regulatory authorities. 
10.8. 
Data Handling and Record Keeping 
Data collection is the responsibility of the clinical study staff at the site under the supervision of 
the site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
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The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into two separate categories: investigator’s study files and subject clinical source 
documents. 
The investigator must maintain source documents for each subject in the study. These source 
documents will consist of case and visit notes (clinical medical records) containing demographic 
and medical information and the results of any tests or assessments. All information on the 
eCRFs must be traceable to the source documents in the subject’s file. Data not requiring a 
written or electronic record will be defined before study start and will be recorded directly on the 
eCRFs, which will be documented as being the source data. 
The records should be retained by the investigator according to ICH guidelines, local regulations, 
or as specified in the Clinical Trial Agreement, whichever retention period is longer. 
Subject data will be entered by site personnel using Medrio, a web-based EDC and reporting 
system. This application will be set up for remote entry. Medrio is the developer and owner of 
Medrio. The EDC software has been fully validated and conforms to Title 21 of the Code of 
Federal Regulations, Part 11 requirements. Investigator site staff will not be given access to the 
EDC system until they have been fully trained. Designated investigator staff will enter the data 
required by the protocol into the eCRFs using this web-based application. Automatic validation 
programs check for data discrepancies in the eCRFs and, by generating appropriate error 
messages, allow modification or verification of the entered data by the investigator staff before 
confirming the data. The investigator must certify that the data are complete and accurate by 
applying an electronic signature to the eCRFs. 
The data collected will be encoded and stored electronically in a database system. Validated data 
may subsequently be transferred to the sponsor. 
10.9. 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical study protocol requirements. The 
noncompliance may be either on the part of the subject, the investigator, or the study site staff. 
As a result of deviations, corrective actions are to be developed by the site and implemented 
promptly. The study monitor must ensure that prompt action is taken to secure compliance. If a 
noncompliance that significantly affects or has the potential to significantly affect human subject 
protection or reliability of study results is discovered, a root cause analysis will be performed, 
and appropriate corrective and preventive actions will be implemented. 
Protocol deviations must be sent to the reviewing IRB per their policies. The investigator is 
responsible for knowing and adhering to the reviewing IRB requirements. 
10.10. 
Publication Policy 
The publication policy will be addressed in the Research and Financial Agreement, and all 
details outlined in the agreement will apply to this protocol. The study will be registered on 
ClinicalTrials.Gov prior to the first subject being dosed. 
 
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Protocol Number 4858-201 
Protocol Version 3.0: 04-Feb-2022 
 
Confidential 
88 of 94 
17. 
 
. 
18. 
 
. 
19. 
 
 
. 
20. 
 
 
. 
21. 
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical 
measure for routine clinical use. Clin Exp Dermatol. 1994;19(3):210-216. 
 
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Protocol Number 4858-201 
Protocol Version 3.0: 04-Feb-2022 
 
Confidential 
89 of 94 
APPENDIX 1. PARTIAL LIST OF STRONG OR MODERATE 
INHIBITORS OF CYP3A4 
 
CYP3A4 Inhibitors 
Strong* 
Moderate 
boceprevir 
aprepitant 
clarithromycin 
ciprofloxacin 
cobicistat 
conivaptan 
idelalisib 
crizotinib 
itraconazole 
cyclosporine 
ketoconazole 
diltiazem 
nefazodone 
dronedarone 
nelfinavir 
erythromycin 
posaconazole 
fluconazole 
ritonavir or any combination medication 
containing ritonavir 
fluvoxamine 
telaprevir 
imatinib 
telithromycin 
tofisopam 
troleandomycin 
verapamil 
voriconazole 
 
*Grapefruit juice is also considered a strong inhibitor of CYP3A4. Please refer to Exclusion 
Criteria 31 for restrictions on grapefruit or grapefruit juice consumption. 
Note: Strong and moderate inhibitors are drugs that increase the AUC of sensitive index 
substrates of a given metabolic pathway ≥5-fold and ≥2 to <5-fold, respectively. 
Adapted from: 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-
table-substrates-inhibitors-and-inducers; accessed 7 Apr 2021 
 
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Protocol Version 3.0: 04-Feb-2022 
 
Confidential 
90 of 94 
APPENDIX 2. PSORIASIS AREA AND SEVERITY INDEX 
 
PASI Scoring 
Four anatomic sites—head, upper extremities, trunk, and lower extremities—are assessed for 
erythema, induration/infiltration (plaque thickness), and desquamation (scaling), as seen on the 
day of the examination. The severity of each sign is assessed using a 5-point scale: 
• 0 = no symptoms 
• 1 = slight 
• 2 = moderate 
• 3 = marked 
• 4 = very marked 
The area affected by psoriasis within a given anatomic site is estimated as a percentage of the 
total area of that anatomic site and assigned a numerical value according to the degree of 
psoriatic involvement as follows: 
• 0 = no involvement 
• 1 = <10% 
• 2 = 10% to <30% 
• 3 = 30% to <50% 
• 4 = 50% to <70% 
• 5 = 70% to <90% 
• 6 = 90% to 100% 
Assignments for the following body regions are as follows: 
• Neck: include with the head. 
• Buttocks: include with the lower extremities. 
• Axillae: include with the trunk. 
• Genitals: include with the trunk. 
• The inguinal canal separates the trunk and legs anteriorly. 
The PASI score for each body region is obtained by using the formula below: 
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 E, I, D, and A denote erythema, induration, desquamation, and area, respectively, and h, 
u, t, and l denote head, upper extremities, trunk, and lower extremities, respectively.  
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Protocol Version 3.0: 04-Feb-2022 
 
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APPENDIX 3. 
 
 
.   
 
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Protocol Version 3.0: 04-Feb-2022 
 
Confidential 
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APPENDIX 4. 
 
 
.   
 
 
 
 
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Pr ot oc ol N u m ber 4 8 5 8 -2 0 1  
Pr ot oc ol Versi o n 3 . 0: 0 4 -Fe b -2 0 2 2  
 
C o nfi de ntial 
9 3 of 9 4 
A P P E N DI X  5.  D E R M A T O L O G Y LI F E Q U A LI T Y I N D E X  
T he ai m of t his q uesti o n n aire is t o me as ure h o w m uc h y o ur s ki n pr o ble m h as affecte d y o ur life 
O V E R T H E L A S T W E E K. Ple ase c hec k o ne b o x f or e ac h q uesti o n.  
1. 
O ver t he last wee k, h o w itc h y, s ore, p ai nf ul  or sti n gi n g has 
y o ur s ki n bee n? 
Ver y m uc h  
A l ot  
A little  
N ot at all  
 
 
 
 
 
2. 
O ver t he last wee k, h o w e m b arr asse d  or self-c o nsci o us  ha ve 
y o u bee n beca use of y o ur s ki n?  
Ver y m uc h  
A l ot  
A little  
N ot at all  
 
 
 
 
 
3. 
O ver t he last wee k, h o w m uc h has y o ur s ki n i nterfere d wit h 
y o u g oi n g s h o p pi n g or l o o ki n g after y o ur h o me  or y ar d ?  
Ver y m uc h  
A l ot  
A little  
N ot at all  
 
 
 
 
 
 
 
N ot 
rele va nt  
4. 
O ver t he last wee k, h o w m uc h has y o ur s ki n i nfl ue nce d t he 
cl ot hes  y o u wear? 
Ver y m uc h  
A l ot  
A little  
N ot at all  
 
 
 
 
 
 
 
N ot 
rele va nt  
5. 
 
O ver t he last wee k, h o w m uc h has y o ur s ki n affecte d a n y 
s oci al or leis ure acti vities?  
  
  
 
Ver y m uc h  
A l ot  
A little 
N ot at all  
 
 
 
 
 
 
 
N ot 
rele va nt  
6. 
O ver t he last wee k, h o w m uc h has y o ur s ki n ma de it diffic ult 
f or y o u t o d o a n y s p ort? 
 
Ver y m uc h  
A l ot  
A little  
N ot at all  
 
 
 
 
 
 
 
N ot 
rele va nt  
7 
 
O ver t he last wee k, has y o ur s ki n pre ve nte d y o u fr o m w or ki n g  
or st u d yi n g? 
Y es 
N o 
 
 
 
 
N ot 
rele va nt  
If “N o ,” o ver t he last wee k h o w m uc h has y o ur s ki n bee n a 
pr o ble m at w or k  or st u d yi n g? 
A l ot  
A little  
N ot at all  
 
 
 
 
 
 
D o c u Si g n E n v el o p e I D: 4 1 9 4 D 1 9 8- F 0 2 D- 4 2 2 9- 8 F 2 3- 7 3 0 3 1 B 7 F 0 A C 2
F or n o n- c o m m er ci al u s e o nl y


Pr ot oc ol N u m ber 4 8 5 8 -2 0 1  
Pr ot oc ol Versi o n 3 . 0: 0 4 -Fe b -2 0 2 2  
 
C o nfi de ntial 
9 4 of 9 4 
T he ai m of t his q uesti o n n aire is t o me as ure h o w m uc h y o ur s ki n pr o ble m h as affecte d y o ur life 
O V E R T H E L A S T W E E K. Ple ase c hec k o ne b o x f or e ac h q uesti o n.  
8. 
O ver t he last wee k, h o w m uc h has y o ur  s ki n create d pr o ble ms 
wit h y o ur p art ner  or a n y of y o ur cl ose frie n ds or rel ati ves? 
  
 
Ver y m uc h  
A l ot  
A little  
N ot at all  
 
 
 
 
 
 
 
N ot 
rele va nt  
9. 
O ver t he last wee k, h o w m uc h has y o ur  s ki n ca use d a n y se x u al 
diffic ulties ?  
 
Ver y m uc h  
A l ot  
A little  
N ot at all  
 
 
 
 
 
 
 
N ot 
rele va nt  
1 0.  O ver t he last wee k, h o w m uc h of a pr o ble m has t he tre at me nt 
f or y o ur s ki n bee n, f or e xa m ple b y ma ki n g y o ur h o me mess y, 
or b y ta ki n g u p ti me?  
Ver y m uc h  
A l ot  
A little  
N ot at all  
 
 
 
 
 
 
 
N ot 
rele va nt  
© A Y Fi nla y, G K K ha n, A pril 1 9 9 2 w w w. der mat ol o g y. or g. u k.  
Ple ase c hec k y o u h a ve a ns were d E V E R Y q uesti o n. T h a n k y o u.  
If t w o or m ore q uesti o ns are left u n a ns were d t he q uesti o n n aire is n ot sc ore d. If t w o o r 
m ore res p o nse o pti o ns are tic ke d, t he res p o nse o pti o n wit h t he hi g hest sc ore s h o ul d be 
rec o r de d. If t here is a res p o nse bet wee n t w o tic k b o xes, t he l o wer of t h e t w o sc o re o pti o ns 
s h o ul d be rec or de d. 
D o c u Si g n E n v el o p e I D: 4 1 9 4 D 1 9 8- F 0 2 D- 4 2 2 9- 8 F 2 3- 7 3 0 3 1 B 7 F 0 A C 2
F or n o n- c o m m er ci al u s e o nl y

SAP_003.pdf: 


 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date: 03-Jun-2018 
        Innovaderm Proprietary & Confidential 
Page 1 of 45 
 
Statistical Analysis Plan 
 
Study Title: 
A Phase 2b, Randomized, Multicenter, Double-Blind, 
Placebo-Controlled, Multiple Dose Study to Evaluate the 
Efficacy, Safety, and Tolerability of NDI-034858 in 
Subjects with Moderate to Severe Plaque Psoriasis 
Protocol Number:  
4858-201  
Protocol Version and Date:  
Version 3.0 (Amendment 2), 04-Feb-2022 
Product: 
NDI-034858 
Sponsor: 
Nimbus Lakshmi, Inc. 
130 Prospect Street, Suite 301 
Cambridge, Massachusetts, United States, 02139 
Telephone: 857-999-2009 
Date: 
 18-Oct-2022 
 
Analysis Plan Version: 
Final v1.0 
 
Prepared by: 
Innovaderm Research Inc. 
3530 boul. Saint-Laurent, suite 300,  
Montreal, Quebec, Canada, H2X 2V1 
 
For non-commercial use only


For non-commercial use only


For non-commercial use only


For non-commercial use only


STATISTICAL ANALYSIS PLAN, Version 
Final v1.0
Protocol Number: 4858-201
Sponsor: Nimbus Lakshmi, Inc. 
SOP-STAT-03-TOOL.01 Version 4
Effective Date: 03-Jun-2018
          Innovaderm Proprietary & Confidential
Page 5 of 45
TABLE OF CONTENT
1 
INTRODUCTION ............................................................................................................10 
2 
STUDY DESCRIPTION...................................................................................................10 
2.1 
Study Design..............................................................................................................10 
2.2 
Treatment Groups.....................................................................................................13 
2.3 
Randomization...........................................................................................................14 
2.4 
Blinding and unblinding............................................................................................14 
3 
STUDY OBJECTIVES AND ENDPOINTS ....................................................................15 
4 
POPULATIONS FOR ANALYSIS ..................................................................................18 
4.1 
Intent-to-Treat Analysis Set......................................................................................18 
4.2 
Modified Intent-to-Treat Analysis Set ......................................................................18 
4.3 
Per-Protocol Analysis Set..........................................................................................18 
4.4 
Safety Analysis Set.....................................................................................................18 
4.5 
Pharmacokinetic (PK) Analysis Set ..........................................................................18 
5 
GENERAL CONSIDERATIONS ....................................................................................19 
5.1 
Sample Size................................................................................................................19 
5.2 
Baseline......................................................................................................................19 
5.3 
Reference Start Date and Study Day ........................................................................19 
5.4 
Analysis windows.......................................................................................................20 
5.5 
Descriptive Statistics .................................................................................................21 
5.6 
Statistical Tests..........................................................................................................21 
5.7 
Handling of Retests, Unscheduled Visits, and Early Termination Data..................21 
5.8 
Software Version .......................................................................................................21 
6 
STATISTICAL CONSIDERATIONS..............................................................................21 
6.1 
Adjustments for Covariates ......................................................................................21 
6.2 
Handling of Dropouts or Missing data .....................................................................22 
6.3 
Interim Analysis and Data Monitoring.....................................................................22 
6.4 
Multiple Comparisons/Multiplicity...........................................................................22 
7 
STUDY SUBJECTS..........................................................................................................23 
7.1 
Disposition of Subjects ..............................................................................................23 
7.2 
Protocol Deviations....................................................................................................23 
7.3 
Demographic and Baseline Characteristics ..............................................................24 
7.4 
Surgical and Medical History ...................................................................................25 
7.5 
Prior and Concomitant Medications.........................................................................26 
7.6 
Study Treatment Exposure and Treatment Compliance .........................................26 
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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0
Protocol Number: 4858-201
Sponsor: Nimbus Lakshmi, Inc. 
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Effective Date: 03-Jun-2018
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10 
PHARMACOKINETIC ANALYSES ..............................................................................41 
11 
............................................................................42 
12 
CHANGES FROM ANALYSIS SPECIFIED IN THE PROTOCOL.............................42 
13 
APPENDICES...................................................................................................................43 
APPENDIX 1.................................................................................................................................43 
APPENDIX 2.................................................................................................................................44 
APPENDIX 3.................................................................................................................................45 
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Protocol Number: 4858-201 
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ABBREVIATIONS 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATC 
anatomical therapeutic chemical 
BMI 
body mass index 
Bpm 
beats per minute 
 
 
CI 
confidence interval 
CMH 
Cochran-Mantel-Haenszel 
COVID-19 
Coronavirus Disease 2019 
CRF 
case report form 
CRO 
contract research organization 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLQI 
Dermatology Life Quality Index 
ECG 
Electrocardiogram 
eCRF  
electronic case report form  
EOS 
end of study 
EOT 
end of treatment 
ET 
early termination 
HR 
heart rate 
ICH 
International Council for Harmonisation 
ITT 
intent-to-treat (analysis set) 
MedDRA  
MH 
Medical Dictionary for Regulatory Activities  
Mantel-Haenszel 
mITT 
modified intent-to-treat (population) 
IWRS 
Interactive Web Response System 
MMRM 
mixed model repeated measures 
 
 
PASI 
Psoriasis Area and Severity Index 
PASI-100 
100% improvement from baseline in Psoriasis Area and Severity Index 
 
 
PASI-75 
75% improvement from baseline in Psoriasis Area and Severity Index 
PASI-90 
90% improvement from baseline in Psoriasis Area and Severity Index 
PD 
Pharmacodynamic 
PGA 
Physician’s Global Assessment 
PK 
pharmacokinetic  
PP 
per protocol (analysis set) 
PT 
preferred term 
QD 
once daily 
QT 
QT interval 
QTcF 
Fridericia’s correction formula for QT interval 
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SAE 
Serious Adverse Event 
SAP
Statistical Analysis Plan 
SAS
Statistical Analysis System®
SE
Standard Error of the Mean
SD
Standard Deviation
SOC
System Organ Class
TEAE
Treatment Emergent Adverse Event 
TLF
Tables, Listings, and Figures
ULN
Upper Limit of Normal 
WHO-DD
World Health Organization Drug Dictionary 
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1 INTRODUCTION 
This Statistical Analysis Plan (SAP) describes the planned analyses and reporting for Nimbus 
Lakshmi, Inc Clinical Protocol 4858-201. Unless otherwise specified, the protocol indicated in this 
SAP is protocol Version 3.0 (Amendment 2), dated 04-Feb-2022. In case of discrepancies between 
the protocol and the SAP, the SAP will be used to guide the statistical analysis. Any deviations 
from the SAP will be described and justified in the final Clinical Study Report (CSR), as 
appropriate. This SAP complies with the International Conference for Harmonization (ICH) E9 
‘Statistical Principles for Clinical Trials’. 
The SAP is designed to outline the methods to be used in the analysis of study data in order to 
answer the study objectives.  Populations for analysis, data handling rules, statistical methods, and 
formats for data presentation are provided. The statistical analyses and summary tabulations 
described in this SAP will provide the basis for the results sections of the clinical study report 
(CSR) for this study. This SAP will be finalized prior to database lock, final unblinding, and final 
analyses. All final analyses will be performed after the clinical trial data are entered into the 
database, any discrepancies in the data are resolved, the database is locked, and following the 
signature of the SAP.  
 
. 
2 STUDY DESCRIPTION 
2.1 Study Design 
Study 4858-201 is a Phase 2b, randomized, multicenter, double-blind, placebo-controlled, multiple-
dose study designed to evaluate the efficacy, safety, and tolerability of NDI-034858 in subjects 
with moderate to severe plaque psoriasis. This study will also evaluate the plasma concentrations 
of NDI-034858 and explore the immune response (in blood and skin) to NDI-034858 in subjects 
with moderate to severe plaque psoriasis. 
Approximately 250 male and female subjects, aged 18 to 70 years (inclusive), with moderate to 
severe plaque psoriasis will be randomized in this study. To be eligible for the study, the subjects 
will need to have a history of plaque psoriasis for at least 6 months prior to the screening visit. In 
addition, the subjects will need to have the following characteristics at screening and on Day 1: 
PASI score ≥ 12, PGA score ≥ 3, and BSA involved with plaque psoriasis ≥ 10%. 
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All subjects will read and sign an informed consent form (ICF) prior to any screening procedures 
being performed. Subjects who fulfill all the inclusion criteria and none of the exclusion criteria 
will be included into the study. During a screening period of no longer than Day -30 to Day -1, 
subjects will be randomized (on Day -7) to receive either one of the four doses of NDI-034858 
(2 mg, 5 mg, 15 mg, or 30 mg), or placebo on Day 1. The goal is to have approximately 50 subjects 
randomized per treatment group (1:1:1:1:1 ratio) on Day 1. During the treatment period, 
NDI-034858 (2 mg, 5 mg, 15 mg, or 30 mg) or placebo will be orally administered QD for 12 
weeks. The 12-week treatment period will be followed by a 4-week safety follow-up period.  
For scheduled study visits, subjects will come to the study site on 8 occasions: screening, Day 1, 
and Weeks 1, 2, 4, 8, 12 (end of treatment [EOT]), and 16 (end of study [EOS] / early termination 
visit [ET]).  
Efficacy will be assessed using PASI, PGA, 
 
 Quality of life will be evaluated 
using DLQI.  
Safety will be assessed by collecting AEs, recording vital signs, performing physical examinations, 
and evaluating clinical laboratory and ECGs results.  
Blood samples will be collected to measure plasma levels of NDI-034858 as follows: 
x On Day 1 prior to dosing and 1 hour (± 5 min) postdosing; 
x At Week 4 prior to dosing, 1 hour (± 5 min) postdosing, and 4 hours (± 10 min) 
postdosing; 
x At Week 8 prior to dosing; 
x At Week 12 anytime (no study treatment administration at this visit).  
x At ET visit anytime (if ET visit is planned before Week 12 visit). 
 
  
 
  
 
 
 
 
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. 
At certain study sites, in a subset of subjects who consent, optional medical photographs of full-
body, front and back, will be taken to illustrate the outcome of the study. 
No interim analysis is planned in this study. 
 
 
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Figure 1: 
Study Diagram 
 
Abbreviation: QD, once daily. 
 
 
2.2 Treatment Groups 
Subjects will receive one of the following treatments for 12 weeks:  
x NDI-034858 2 mg, QD  
x NDI-034858 5 mg, QD 
x NDI-034858 15 mg, QD 
x NDI-034858 30 mg, QD 
x Placebo, QD 
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2.3 Randomization 
At the study site, each screened subject will be assigned a subject identifier number during 
screening that will be used on all subject documentation. The subject identifier number will contain 
the site number and the subject number and will be assigned in numerical order at the screening 
visit based on chronological order of screening dates (e.g., 02010 for the 10th subject screened at 
Site 02). 
Approximately 250 subjects will be randomized 1:1:1:1:1 ratio to NDI-034858 at 2 mg, 5 mg, 
15 mg, or 30 mg, or placebo (approximately 50 subjects per treatment group).  
Randomization will occur at Day -7 visit. The randomization list will be generated using a 
validated software and will be stratified based on prior treatment with biologics (yes/no). The 
master randomization list will be kept secured until the study blind is broken at the end of study. 
This list will be uploaded into an Interactive Web Response System (IWRS). The investigator or 
designee will be able to acquire a randomization number for subjects by connecting to the IWRS. 
Of note, only eligible subjects (confirmed on Day 1) will receive the study treatment.  
Subjects randomized but never dosed can be replaced when early terminated. 
Further guidance and information can be obtained in the study manual. 
2.4 Blinding and unblinding 
This study is double-blinded. At all times, treatment and randomization information will be kept 
confidential and will not be released to the investigator, the study staff, the contract research 
organization (CRO), or the sponsor’s study team until after the study completion. 
Breaking the blind should be considered only when knowledge of the treatment assignment is 
deemed essential for the subject’s care. In cases of accidental unblinding, the investigator should 
contact the medical monitor and ensure every attempt is made to preserve the blind.  
The subject for whom the blind has been broken for a safety-related reason will be permanently 
discontinued from the study treatment. The primary reason for study treatment discontinuation 
(the event or condition which led to the unblinding) will be recorded. 
 
 
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OBJECTIVES 
ENDPOINTS 
To assess the safety and 
tolerability of NDI-034858 
orally administered QD at 
2 mg, 5 mg, 15 mg, or 
30 mg for 12 weeks in 
subjects with moderate to 
severe plaque psoriasis 
x Incidence of AEs 
x Changes from baseline in vital signs, clinical laboratory 
parameters, and ECGs 
To evaluate the plasma 
concentration of 
NDI-034858 orally 
administered QD at 2 mg, 
5 mg, 15 mg, or 30 mg in 
subjects with moderate to 
severe plaque psoriasis 
Secondary Pharmacokinetic Endpoint 
x Measurement of plasma concentrations of NDI-034858 in 
subjects receiving active treatment  
Exploratory Objectives 
Exploratory 
 Endpoints 
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OBJECTIVES 
ENDPOINTS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Exploratory 
 Endpoints 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AE, adverse event; 
; DLQI, Dermatology Life Quality 
Index; ECG, electrocardiogram;
; 
PASI, Psoriasis Area and Severity Index; PASI-100, 100% improvement from baseline in PASI; 
; PASI-75, 75% improvement from baseline 
in PASI; PASI-90, 90% improvement from baseline in PASI; PGA, Physician’s Global 
Assessment; QD, once daily. 
. 
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4 POPULATIONS FOR ANALYSIS 
4.1 Intent-to-Treat Analysis Set 
The intent-to-treat (ITT) analysis set will include all subjects who were randomized. All subjects 
will be analyzed according to the treatment group to which they were randomized.  
4.2 Modified Intent-to-Treat Analysis Set 
The modified intent-to-treat (mITT) analysis set will include all subjects who were randomized 
and received at least one dose of study treatment. All subjects will be analyzed according to the 
treatment group to which they were randomized. The mITT analysis set will be used as the primary 
analysis population for efficacy. 
4.3 Per-Protocol Analysis Set 
The per-protocol (PP) analysis set will include all subjects who were randomized, who received at 
least one dose of study product, and who provided evaluable data for the primary endpoint (PASI-
75 at Week 12) with no major protocol deviations affecting the efficacy evaluations as defined in 
Appendix 3. All subjects will be analyzed according to the treatment group that they actually 
received. The primary efficacy analysis will be repeated based on the per protocol analysis set if 
it differs by more than 10% in number of subjects from the mITT analysis set. Details of major 
protocol deviations are provided in Appendix 3. The PP analysis set will be used as a 
supplementary analysis of the primary endpoint.  
4.4 Safety Analysis Set 
The safety analysis set will include all subjects who received at least one dose of the study product. 
All subjects will be analyzed according to the treatment group that they actually received. 
4.5 Pharmacokinetic (PK) Analysis Set 
The pharmacokinetic (PK) analysis set will include all subjects who received at least one dose of 
NDI-034858 and have evaluable plasma concentration data. All subjects will be analyzed 
according to the treatment group that they actually received. 
. 
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5 GENERAL CONSIDERATIONS 
Formats and layouts of tables, listings, and figures (TLF) will be provided in a separate document 
(output general layout is described in Appendix 1). 
Unless otherwise noted, all statistical summaries will be done by treatment group and by visit, as 
applicable.  
5.1 Sample Size 
The sample size determination is based on testing equality of two independent response rates using 
a 2-sided test with significance level of alpha = 0.05 and power 85%. The formula used for the 
calculation is the same as used in the nQuery® (ie, normal approximation with Fleiss’ formula and 
continuity correction). 
Assuming the placebo response rate at end of Week 12 is 10% (proportion of subjects achieving 
PASI-75), at least one of the NDI-034858 dose treatment groups will have a response rate at least 
40%, and after adjustment of 15% dropout rate between randomization and Day 1, approximately 
250 subjects (50 per treatment group) will be randomized in the study. 
5.2 Baseline 
Unless otherwise specified, baseline value will be defined as the last non-missing assessment prior 
to or on the first study treatment dosing (including unscheduled assessments) or randomization if 
no study drug is given. If the last non-missing assessment is performed on the same date as the 
first study treatment administration (or randomization if no study drug is given) and time is not 
available, the assessment will be considered as baseline, except for adverse events (AEs) not 
related to a pre-dose assessment and medications starting on the first study treatment dose 
administration date which will be considered post-baseline. 
5.3 Reference Start Date and Study Day 
Study day will be calculated from the first study treatment administration date and will be used to 
show start/end day of assessments or events.  
Study day = (Date of event – Date of first dose administration) + 1 if date of event is on or after 
the date of first dose administration of study treatment; 
= (Date of event – Date of first dose administration) if date of event is before the date 
of first dose administration of study treatment. 
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5.5 Descriptive Statistics 
All continuous variables will be summarized by presenting the number of subjects, mean, standard 
deviation (SD), median, minimum, maximum, Q1 and Q3. Categorical variables will be presented 
as frequencies and percentages. Summary tables will be presented by treatment and by visit, when 
applicable. 
Change from baseline will be calculated as:  
Assessment value at postbaseline visit X – baseline value. 
Percent change from baseline (%) will be calculated as: 
(Assessment value at postbaseline visit X – baseline value) / baseline value * 100. 
Percent change from baseline will be missing in situation where baseline value equals to 0. 
5.6 Statistical Tests 
Unless otherwise specified, all statistical tests will be two-sided and will be performed with a 
significant level of 0.05. Confidence intervals (CIs) will be two-sided with 95% coverage. 
5.7 Handling of Retests, Unscheduled Visits, and Early Termination Data 
When retests measurements are done, the retest measurement will be considered for the summary 
analysis. All data from retest visits will be listed. 
Unscheduled and early termination assessments will be remapped as defined in section 5.4.  
5.8 Software Version 
All analyses will be performed using SAS® software Version 9.4 or higher. 
6 STATISTICAL CONSIDERATIONS 
6.1 Adjustments for Covariates 
Baseline value will be included as covariate in the statistical models for the analysis of the 
continuous efficacy endpoints on change and percent change from baseline using Mixed Model 
for Repeated Measures (MMRM ) models (PASI, PGA, 
, DLQI 
). 
The odds ratio and difference in proportion of subjects achieving binomial endpoints between 
treatment group and placebo will be adjusted by prior treatment with biologics.  
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6.2 Handling of Dropouts or Missing data 
See Appendix 2 for handling of completely or partially missing dates for prior and concomitant 
medications and AEs. 
Unless otherwise specified, missing safety data will not be imputed. 
For the categorical efficacy endpoints (e.g., proportion of subjects achieving at least a 75% 
improvement from baseline in PASI), subjects with a missing assessment at a specific visit will be 
considered as not having achieved the endpoint at that visit, and as not having achieved the 
endpoint for subsequent visits for discontinued subjects. For logistic regression models, missing 
values will not be imputed as non-responders and will be left as missing. 
Missing observations for the efficacy continuous endpoints will be addressed by using the mixed 
model for repeated measures (MMRM) approach. The parameter estimations are based on the 
assumption of data being missing at random and using the method of restricted maximum 
likelihood (REML).  
6.3 Interim Analysis and Data Monitoring 
No interim analysis is planned for this study. 
6.4 Multiple Comparisons/Multiplicity 
All statistical tests will be two-sided and will be performed with a significant level of 0.05, unless 
otherwise specified. To account for the multiplicity testing in the primary endpoint analysis, each 
active treatment group will be compared to the placebo group using a hierarchical testing 
procedure, starting with the highest dose group, and ending with the lowest dose group (30-mg 
NDI-034858, 15-mg NDI-034858, 5-mg NDI-034858, and 2-mg NDI-034858, in order). If a 
comparison is not significant at level 0.05, all p-values in subsequent comparisons will be 
considered to be nominal and may be provided if applicable. No adjustment to alpha will be made 
to account for multiple testing between treatment groups for the secondary 
 
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7 STUDY SUBJECTS 
 
7.1 Disposition of Subjects 
All subjects who provide informed consent will be accounted for in this study. The number of 
subjects screened, rescreened, and who failed screening (screen failures) will be presented. The 
reason for screen failure will be presented for all screened subjects who failed screening and 
rescreening, if applicable. Moreover, the number of subjects randomized, the number of subject 
randomized but early terminated (ET) or lost-to-follow-up (LTFU) (i.e. discontinued) before first 
study treatment dose and associated reason, and the number of subjects included in each analysis 
set will be presented. Study completion status and the reason for study discontinuation, including 
related to COVID-19 or not, will also be presented. The percentage of subjects with screen failures 
will be calculated using the number of subjects screened as denominator. The percentage of screen 
failure by reasons will be calculated using the number of screen failures as denominator. The 
percentage of subjects with study discontinuation will be calculated by reasons using the number 
of subjects who did not complete study as denominator (and due to COVID-19 or not, as 
applicable). Otherwise, percentages will be calculated using the number of subjects randomized 
and dosed as denominator. Number of days in the study will be calculated as follows and 
summarized: 
 
Number of days in study = Date of completion/discontinuation – 1st dose date +1 
For subject who did not receive a dose of study treatment, the number of days in the study will be 
left as missing. 
A listing of subject’s disposition will be provided. Information on first screening for subjects who 
were rescreened, including the rescreened subject identifier and the reason for first screening 
failure, will be presented under the first screening subject identifier.  
A listing of subject’s randomization information, a listing subject randomized but deemed not 
eligible or lost-to-follow-up (i.e. discontinued) before receiving a first study treatment dose, and a 
listing of subjects included in each of the analysis sets will also be provided. 
7.2 Protocol Deviations 
A data review will be conducted prior to database lock and unblinding of treatment assignment by 
the Medical Monitor, Statistician and the Sponsor to classify protocol deviations as minor or major 
as defined in Appendix 3. Protocol deviations, including classification as Important/Non-
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Important, will be classified as described in the Protocol Deviation Management Plan, based on 
Nimbus categorization. 
The number of events and the number and percentage of subjects with at least one major protocol 
deviation (including major protocol deviations associated with COVID-19) will be summarized 
by deviation category, sub-category and treatment group using the safety analysis set. Important
protocol deviations will be summarized separately in a similar way. A listing of all protocol 
deviations (including minor) will also be provided on the safety analysis set.
In addition, all the protocol deviations associated with COVID-19 will be summarized by deviation 
category and deviation sub-category and listed as described above. Protocol deviations will be 
sorted alphabetically by categories and within each category the sub-categories will be presented 
by decreasing order.
7.3 Demographic and Baseline Characteristics
Demographics and baseline characteristics will be summarized with descriptive statistics using the
ITT, mITT and safety analysis set (if different from mITT) by treatment group and overall. The 
list of demographics and baseline characteristics to be summarized will include: 
x
Age at consent (years) 
x
Sex 
x
Race*
x
Ethnicity
x
Baseline Height (cm)
x
Baseline Weight (kg) 
x
Baseline BMI (kg/m2) **
x
Prior Treatment with Biologics (Yes/No)
x
Psoriasis Area and Severity Index 
x
Physician Global Assessment
x
Body Surface Area (%)
x
Pruritus Numeric Rating Scale
x
Dermatology Life Quality Index
x
Pain Numeric Rating Scale for subjects with concomitant psoriatic arthritis at baseline
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*Subjects who reported more than one race will be summarized as ‘Multiple’ races in the table.
All races selected will be displayed in the listing.
** Baseline BMI is calculated by using baseline height and baseline weight. 
A listing of all demographics and baseline characteristics will be provided on the ITT analysis set.
7.4 Surgical and Medical History
Surgical and medical history will be coded according to the Medical Dictionary for Regulatory 
Activities (MedDRA), Version 24.0.
Surgical and medical history (including disease-specific medical history) will be summarized by 
system organ class (SOC) and preferred term (PT) using the safety analysis set. A subject who 
experienced the same surgical and medical history event multiple times will be counted only once 
for the corresponding PT. Similarly, if a subject experienced multiple surgical and medical history 
events within the same SOC, the subject will be counted only once for that SOC. Surgical and 
medical history events will be sorted alphabetically by SOC and within each SOC the PT will be 
presented by decreasing order.
A listing of all surgical and medical history events will be provided.
Disease-specific medical history for the duration of plaque psoriasis and psoriatic arthritis will be 
summarized using the safety analysis set. 
The disease duration for plaque psoriasis and psoriatic arthritis (in years) will be calculated as 
follows:
Disease duration of plaque psoriasis or psoriatic arthritis = (Date of first dose of study treatment –
Start date of plaque psoriasis or psoriatic arthritis)/365.25.
Completely or partially missing dates for the start date of plaque psoriasis or psoriatic arthritis will 
be imputed as follows:
x
Completely missing: Leave missing. 
x
Missing day and month: Impute to January 1st. 
x
Missing day: Impute to the 1st of the month.
Disease-specific medical history will be listed.
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7.5 Prior and Concomitant Medications 
Medications will be coded according to the World Health Organization Drug Dictionary 
(WHO-DD), March 2021 B3. 
Prior medications are defined as any medication started and discontinued prior to the first study 
treatment dosing. Concomitant medications are defined as any medication taken after the first 
study treatment dosing, including those who started prior to the first study treatment date and 
continued past that date. See Appendix 2 for handling of completely or partially missing dates for 
prior and concomitant medications.  
Incidence of prior and concomitant medications will be tabulated by anatomical therapeutic 
chemical (ATC) level 3 and PT using the safety analysis set. A subject with the same medication 
taken multiple times will be counted only once for the corresponding PT. Similarly, if a subject 
has taken more than one medication within the same ATC level, then the subject will be counted 
only once for that ATC. Prior and concomitant medications will be sorted alphabetically by ATC 
level and within each ATC level, the PT will be presented by decreasing order.   
A listing of all prior and concomitant medications will be provided. 
7.6 Study Treatment Exposure and Treatment Compliance 
Duration of exposure to study treatment, in days, will be computed as follows: 
 
Duration of exposure = [(Date of last dose of study treatment – Date of first dose of study 
treatment) + 1] 
 
Compliance with study treatment (%) will be calculated as follows: 
 
Number of doses taken
Total extent of exposure (in days) * Planned number of doses per day ൈͳͲͲ 
 
For each subject, the planned number of doses per day corresponds to one dose per day. 
Daily doses from the first dose of study treatment until the last dose of study treatment will be 
assumed as taken unless they are entered as missed doses in the diary. Missed doses with unknown 
dates will be considered as being missed between the first dose and last dose of study treatment. 
Descriptive statistics for the duration of exposure and compliance to study treatment, and number 
of missed doses, will be presented by treatment group and overall based on the safety analysis set. 
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Frequency distribution will also be presented for the following compliance categories: <80%, 80% 
to 120%, >120%. The number and proportions of subjects in each study drug exposure category 
will be summarized using the following categories: ≤4 weeks (≤28 days), 4 weeks to ≤8 weeks 
(>28 to ≤56 days), 8 weeks to ≤12 weeks (>56 to ≤84 days), >12 weeks (>84 days), based on the 
number of subjects in the safety analysis set.  
Listings of all study treatment administrations at the study site and missed doses as per diary, study 
drug accountability, and study treatment compliance and exposure will be provided on the safety 
analysis set. Additionally, a listing of study treatment overdose will be provided by subject on the 
safety analysis set. 
8 EFFICACY ANALYSIS 
8.1 Imputation of Values Due to Prohibited Medications  
For all efficacy endpoints, any subject’s assessment collected on the day of the start of a prohibited 
medication or after which was adjudicated as major protocol deviation (Appendix 3) will be set as 
missing (for continuous endpoints) and non-responder (for binary endpoints, including in logistic 
regression models) for the purpose of the efficacy analyses. 
 
8.2 Analysis of Primary Efficacy Endpoint 
8.2.1 Psoriasis Area and Severity Index (PASI) 
The PASI quantifies the severity of a subject’s psoriasis based on both lesion severity and the 
percentage of BSA affected. The PASI is a composite score ranging from 0 to 72 that that takes 
into account the degree of erythema, induration/infiltration, and desquamation (each scored from 
0 to 4 separately) for each of four body regions, with adjustments for the percentage of BSA 
involved for each body region and for the proportion of the body region to the whole body. Scoring 
of the PASI is presented in protocol Appendix 2. The PASI score will be set as missing if at least 
one question value is missing. 
 
8.2.2 PASI-75 
The percentage change from baseline in PASI at Week 12 will be calculated using the following 
formula:  
௉஺ௌூ௦௖௢௥௘௔௧ௐ௘௘௞ଵଶି௉஺ௌூ௦௖௢௥௘௔௧஻௔௦௘௟௜௡௘
௉஺ௌூ௦௖௢௥௘௔௧஻௔௦௘௟௜௡௘
כ ͳͲͲ  
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For a subject, achievement of PASI-75 is Yes if the percentage change from baseline is less than 
or equal to -75%, i.e., the subject has greater than or equal to 75% improvement in PASI score 
comparing to baseline. Otherwise, PASI-75 is No. 
The primary endpoint is defined as follow: 
x Proportion of subjects achieving at least a 75% improvement from baseline in Psoriasis 
Area and Severity Index (PASI-75) at Week 12. 
8.2.3 Primary Analysis 
The primary endpoint will be translated as a responder analysis, where a subject will be classified 
as responder if he or she achieves PASI-75 at Week 12. The primary efficacy analysis will be 
performed on the mITT analysis set. 
Subjects with a missing postbaseline PASI results at Week 12 will be considered as not having 
achieved the PASI-75 at that Week 12 (i.e., as non-responder).  
The following analyses will be provided for PASI-75: 
x Descriptive statistics (frequencies and percentages) for PASI-75 will be presented by visit 
and treatment group.  
x A longitudinal line plot of the response rate in PASI-75 by treatment group will be 
provided. 
x The comparison between treatment groups (each active group vs placebo) will be done 
using a Cochran-Mantel-Haenszel (CMH) as the primary analysis, with prior treatment 
with biologics (Yes/No) included as a stratification factor. The odds ratio (odds in 
treatment group/odds in placebo) and the difference in the response rates calculated using 
the Mantel-Haenszel stratum-weighted method and their corresponding two-sided 95% 
confidence intervals (CIs) will be provided. If a subject is stratified incorrectly at 
randomization, the subject will be included into the analysis as stratified per the ITT 
principle.  
To account for the multiplicity testing in the primary endpoint analysis, each active 
treatment group will be compared to the placebo group using a hierarchical testing 
procedure, starting with the highest dose group and ending with the lowest dose group (30-
mg NDI-034858, 15-mg NDI-034858, 5-mg NDI-034858, and 2-mg NDI-034858, in 
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order). If a comparison is not significant at level 0.05, all p-values in subsequent 
comparisons will be considered to be nominal and may be provided if applicable.  
 
8.2.4 Supplementary Analysis 
A logistic regression model analysis will be performed to evaluate the impact of treatments on 
PASI-75 at Week 12, with treatment group, age, gender, baseline weight, baseline BMI, baseline 
PASI score, and use of previous biologic treatment as covariates. Subjects with missing value 
will not be imputed to non-responders and will be left as missing for the purpose of this analysis. 
To test the robustness of the analysis method, the primary analysis of the proportion of subjects 
achieving PASI-75 will be repeated using the ITT analysis set as a supplementary analysis.  It will 
also be repeated using PP analysis set if it differs by more than 10% from the mITT analysis set.  
Additionally, a repeat of the primary endpoint analysis will be performed based on Observed Cases 
(OC) only, i.e. excluding the imputed values as non-responders. 
8.2.5 Subgroup analysis 
To investigate the impact of the use of previous biologic treatment on the primary efficacy  
endpoint, subgroup analyses will be performed. The Chi-square test on the response rates in PASI-
75 at Week 12 will be conducted and the odds ratio (odd in a treatment group/odd in placebo) in 
the response rates and its corresponding two-sided 95% CI will be provided. 
8.3 Analyses of Secondary Efficacy Endpoints 
All secondary endpoint analyses will be conducted using the mITT analysis set. 
8.3.1 PASI-90 and PASI-100 
The secondary efficacy endpoints involving proportion of subjects on PASI include PASI-90 and 
PASI-100. PASI-90, and PASI-100 are defined as at least 90%, and 100% improvement from 
baseline in PASI, respectively. PASI-90 and PASI-100 are defined similarly as PASI-75 in Section 
8.1.2.  
The PASI-90 and PASI-100 will be analyzed as follow using the mITT analysis set: 
x Proportion of subjects achieving PASI-90 at Week 12, 
x Proportion of subjects achieving PASI-100 at Week 12. 
 
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8.3.2 Physician’s Global Assessment 
The PGA of disease severity is a global assessment of the current state of the disease. It is a 5 -point 
morphological assessment of overall disease severity (0-Clear, 1-Almost clear, 2-Mild, 3-
Moderate, 4‑Severe). 
The secondary endpoints on PGA will be analyzed as follow using the mITT analysis set: 
x Proportion of subjects achieving a PGA of clear (0) or almost clear (1) at Weeks 12. 
8.3.3 Dermatology Life Quality Index Questionnaire  
The DLQI is a simple 10‑question validated questionnaire that has been used in more than 40 
different skin conditions. The DLQI is the most frequently used instrument in studies of 
randomized controlled trials in dermatology. Each question is scored on a four-point Likert scale: 
very much (3); a lot (2); a little (1); not at all (0); and not relevant (0). DLQI total score is defined 
as the sum of the 10 item scales, ranging from 0 to 30. If missing answers, the following rules will 
be followed:
x If one question is left unanswered, then the question is scored as 0 and the scores are 
summed and expressed as usual out of a maximum of 30. 
x If two or more questions are left unanswered, then the questionnaire is not scored. 
x If question 7 is answered ‘yes’, then this is scored as 3 (even if in the same question one of 
the other boxes is ticked). 
x If question 7 is answered ‘no’ or ‘not relevant’ but then either ‘a lot’ or ‘a little’ is ticked, 
then this is scored as 2 or 1. If it is answered ‘no’, but the second half is left incomplete, 
the score will remain 0. 
The secondary endpoint on the DLQI total score will be analyzed as follow on the mITT analysis 
set: 
x Change from baseline in DLQI at Week 12. 
Additionally, the number of subjects achieving a score of 0 or 1 will be descriptively summarized 
at each visit, with no imputation for missing values. 
8.3.4 Analysis of Secondary Endpoints  
For endpoints involving proportions of subjects, subjects with a missing postbaseline assessment 
at a specific visit will be considered as not having achieved the endpoint at that visit (and as not 
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having achieved the endpoint for subsequent visits for discontinued subjects), i.e., as non-
responders. 
The following analyses will be provided for the secondary endpoints of PASI-90, PASI-100, and 
proportion of subjects achieving a PGA of clear (0) or almost clear (1):  
x PASI-90 and PASI-100, and the achievement of PGA score of 0/1 (0-Clear, 1-Almost 
Clear) will be presented using descriptive statistics (frequency and percentage) by visit 
for each group. 
x A longitudinal line plot of the response rate in PASI-90, PASI-100 and achievement of 
PGA of 0/1 by treatment group will be provided. 
x The comparison between treatment groups (each active group vs placebo) will be 
analyzed using the same approach (CMH test) as described for the primary efficacy 
analysis, at each visit.  
x As a supplementary analysis, a logistic regression model analysis will be performed to 
evaluate the impact of treatments on achievement of PGA score of 0/1 at Week 12, with 
treatment group, age, gender, baseline weight, baseline BMI, baseline PASI score, and 
use of previous biologic treatment as covariates. Subjects with missing value will not be 
imputed to non-responders and will be left as missing for the purpose of this analysis. 
No adjustments for multiple comparisons for secondary outcomes will be made.  
The following analyses will be provided for the secondary endpoints of DLQI:  
x Descriptive statistics on DLQI will be presented by visit and treatment group.  
x Change from baseline will also be summarized descriptively by visit and treatment group.  
x The change from baseline in DLQI will be analyzed using an MMRM. The model will 
include treatment group, visit (Weeks 4, 8, and 12), treatment-by-visit interaction, and prior 
treatment with biologics as fixed effects, and baseline score as a covariate. Unstructured 
covariance will be used to model the within-subject error. If convergence issues arise, the 
autoregressive (AR(1)) structure will be used. If the AR(1) structure also does not 
converge, other covariance structures (CS, Toeplitz) deemed appropriate to fit the data will 
be used. The Kenward Roger method will be used for computing the denominator degrees 
of freedom for the tests of fixed effects. The treatment effect will be the contrast between 
treatment groups at each scheduled post-baseline visit estimated through least squares (LS) 
means. The LS mean estimates, LS mean differences, associated two-sided 95% 
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confidence intervals, and p-values will be reported. The contrasts of interest will be of each 
active treatment group (2, 5, 15 and 30 mg NDI-034858) vs placebo group. 
 
8.4 Analyses of Exploratory 
 Endpoints 
8.4.1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.4.2 
 
 
 
 
 
 
 
 
8.4.3 
 
 
 
 
 
 
 
 
 
 
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9 SAFETY ANALYSIS 
All safety analyses will be conducted using the safety analysis set. No inferential statistics will be 
performed on safety variables. 
9.1 Adverse Events 
The primary focus of adverse event reporting will be on treatment-emergent adverse events 
(TEAEs).  Pretreatment adverse events will be provided separately, in applicable listings.  
Adverse events (AEs) will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA), Version 24.0. 
Listings of all AEs, all AEs leading to death, all serious AEs, all TEAEs leading to study treatment 
discontinuation, all TEAEs leading to study discontinuation, AE of CPK elevation and AE of 
special interest will be provided. All information pertaining to AEs noted during the study will be 
listed by treatment group, subject, detailing verbatim, system organ class, preferred term, start 
date, stop date, intensity, outcome, action taken with respect to study product, and relationship to 
study product. The AE onset will also be shown relative (in number of days) to the day of study 
product administration.  
Treatment emergent adverse events (TEAEs) will be derived as any AEs with onset date on or 
after the first study treatment dosing. AEs starting on the first study treatment dosing date and 
related to a pre-dose study assessment will not be considered as TEAE. See  
 
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Appendix 2 for handling of completely or partially missing dates for AEs. In the case where it is 
not possible to define an AE as treatment emergent or not, the AE will be classified as treatment 
emergent. 
An overall summary table of adverse events will be provided. The number of events and the 
number and percentage of subjects who experienced TEAE, AE of special interest (AESI), TEAE 
by worst reported relationship, TEAE by worst reported severity, related TEAE by worst reported 
severity, serious AE (SAE), serious TEAE by worst reported severity, TEAE leading to study 
treatment discontinuation, TEAE leading to study discontinuation, and AE leading to death will 
be presented. 
Unless otherwise specified, a subject experiencing the same TEAE multiple times will be counted 
only once for the corresponding preferred term (PT). Similarly, if a subject experiences multiple 
TEAEs within the same system organ class (SOC), the subject will be counted only once for that 
SOC. TEAEs will be sorted alphabetically by SOC and within each SOC the PT will be presented 
by decreasing order. 
A treatment-related TEAE is defined as any TEAE that is assessed by the investigator as related 
to study treatment. TEAE that is assessed as not related will be defined as not treatment-related. If 
a subject experiences more than one TEAE within different relationship categories within the same 
SOC/PT, the subject will be counted only once for that SOC in the worst reported relationship 
category. A TEAE with an unknown relationship will be considered as treatment-related. 
The severity of an AE or SAE is based on the National Cancer Institute (NCI) CTCAE, Version 
5.0. A life-threatening or fatal adverse event is defined as any adverse events with a severity grade 
of 4 or higher (grade 4 (life-threatening) or grade 5 (fatal)). If a subject experiences more than one 
TEAE within different severity categories within the same SOC/PT, the subject will be counted 
only once for that SOC and the highest severity category. TEAE with an unknown severity will be 
considered as severe. 
Adverse event incidence tables will present by primary SOC and PT for each treatment group, the 
number (n) and percentage (%) of participants experiencing the following:    
x All TEAEs 
x Treatment-related TEAEs  
x TEAEs leading to discontinuation of study treatment 
x TEAEs leading to study discontinuation 
x TEAEs by severity (CTCAE grades 1, 2, 3, 4 or higher) 
x TEAEs leading to death 
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x
Treatment-emergent SAEs
x
Treatment-related SAEs
x
Treatment-emergent AESIs (as defined in Protocol section 8.4.7) 
x
Treatment-related AESIs 
TEAEs will also be summarized by the following periods:
-
The “On-treatment period” is defined as a TEAE with onset date from the date from 
first administration of study treatment to the last dose of treatment date (included).
-
The “Post-treatment period” is defined as a TEAE with onset date from the last dose 
of treatment date + 1 to the end of study.
9.2 Clinical Laboratory
Descriptive statistics will be presented for data related to biochemistry ,hematology, coagulation,
quantitative urinalysis, fasted lipids and lipids (including both fasted and non-fasted). Change from 
baseline values will be presented for each postbaseline assessment. Frequencies and percentages 
for each result will be provided for qualitative urinalysis data.
For fasted lipids, if the fasting status is unknown, it will be assumed that the subject did not fast. 
Clinical laboratory results were graded with CTCAE grading report flag in laboratory service 
agreement LSA Medpace. CTCAE grading will not be derived for local laboratory results. Shift 
tables from baseline to each postbaseline assessments describing shifts in CTCAE grade will be 
provided as well for biochemistry, hematology, coagulation, fasted lipids and lipids (including 
both fasted and non-fasted). Only subjects with a baseline result and a result at the specified visit 
for the parameter will be considered. Additionally, shift tables from baseline to each postbaseline 
assessments describing shifts to out-of-normal range will be provided for qualitative urinalysis.
The shift from baseline to maximum post-baseline CTCAE grade will also be reported.
In addition to the laboratory results reported by the laboratory service, other parameters will be 
derived. 
The corrected calcium will be calculated and reported using the following formula:
Corrected Calcium (mmol/L)= Serum Calcium (mmol/L) + 0.02 * (40 – Patient Albumin in g/L)
Corrected calcium will be graded using CTCAE Grade v5.0 and reported as part of the 
biochemistry assessments.
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For protein urine, a shift table from baseline to each post-baseline assessment describing the shift 
in value will be produced, based on the following categories: 0/Trace (Negative or ≤20 mg/dL), 
1+ (>20 and ≤70 mg/dL) , 2+ (> 70 and ≤200 mg/dL) , 3+ (>200 and ≤600 mg/dL), 4+ (>600 
mg/dL). The shift from baseline to maximum post-baseline value will also be reported. Protein 
urine will be graded using CTCAE Grade v5.0 and reported as part of the urinalysis assessments. 
A shift table will also be produced for eGFR. eGFR will be derived at each visit using creatinine 
value: 
 
eGFR (ml/min)= [(140 − Age) × Weight in kg/(72 × sCr)] × (0.85 if female). 
Where weight is in kg, and Creatinine (sCr) is in mg/dL. If any value of this equation is missing 
for subject or visit, eGFR will be left as missing. The shift from baseline to worst post-baseline 
value will also be reported. 
Separate listings of all data for biochemistry, hematology, coagulation, urinalysis, lipids and 
pregnancy test will be provided. 
Frequency and percentage of subjects who experience treatment-emergent CTCAE Grade 1 or 
higher will be summarized for the following CTCAE terms: Anemia, Lymphocyte count 
decreased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased, 
Hypoalbuminemia, Hypoglycemia, Activated partial thromboplastin time prolonged, INR 
increased, Alanine aminotransferase increased, Aspartate aminotransferase increased, GGT 
increased, Alkaline phosphatase increased, Blood bilirubin increased, CPK increased, Cholesterol 
high, Hypertriglyceridemia, Creatinine increased, Hypocalcemia, Hypercalcemia, Hyponatremia, 
Hypernatremia, Hypokalemia, Hyperkalemia.. A similar table will be produced for treatment-
emergent CTCAE Grade 2 or higher. Subjects experiencing multiple events within the same 
CTCAE term will be counted only once for that CTCAE term. 
For the CTCAE terms mentioned above, a separate listing will be provided for each parameter 
where a subject had at least one clinically significant treatment-emergent (Grade 2 or higher) 
abnormal result. 
Local laboratory results will be analyzed as other laboratory results. 
9.3 Vital Signs  
Descriptive statistics will be presented for data related to vital signs (systolic blood pressure 
diastolic blood pressure, pulse rate, and body temperature). Change from baseline values will be 
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presented for each post baseline assessment. Descriptive statistics will be presented for height, 
weight and BMI, including change from baseline for weight and BMI. 
Tables describing abnormal results will be provided as well, based on the abnormality criteria in 
Table 2. Only subjects with a baseline result and a result at the specified visit for the parameter 
will be considered. 
A listing of all vital sign assessments will be provided. 
The following criteria will be used to determine vital sign results that are outside of a prespecified 
range of normality:  
Table 2: Vital Sign Parameter Cut-Off Values 
Parameter 
Criteria 
Pulse Rate (bpm) 
Value > 100 and change from baseline > 30, or 
Value < 55 and change from baseline < -15 
Systolic blood pressure (mmHg) 
Value > 140 and change from baseline > 20, or 
Value < 90 and change from baseline < -20 
 
Diastolic blood pressure (mmHg) 
Value > 90 and change from baseline > 10, or 
Value < 55 and change from baseline < -10 
 
 
In addition, participants with vital signs outside of this pre-specified range of normality (i.e., Table 
2) will also be listed. 
9.4 Physical Examination 
A listing of all physical examinations will be provided.  
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9.5 Electrocardiogram 
Descriptive statistics will be presented for data related to ECGs (heart rate, RR, PR, QRS, QT, 
QTcB and QTcF). Change from baseline values will be presented for each postbaseline 
assessment.  
A listing of all ECG assessments will be provided. 
The incidence of QTc prolongation (defined as QTcF or QTcB >= 480 or >=30 msec increase from 
baseline) at any time during the treatment-emergent adverse event period will be summarized by 
treatment group. A separate listing for the subjects with QTc prolongation will be provided.  
 
9.6 Potential Drug Induced Liver Injury 
Potential Drug Induced Liver Injury (DILI) are defined as alanine aminotransferase (ALT) or 
aspartate aminotransferase (AST) values ≥ 3 times the upper limit of normal (ULN) and total 
bilirubin > 2 times the ULN. A listing will be provided for potential drug induced liver injury by 
subject. 
 
9.7 Consultation Notes 
Consultation notes will be listed based on the safety analysis set. 
10 PHARMACOKINETIC ANALYSES 
Blood samples will be collected to measure plasma levels of NDI-034858 as follows:  
x On Day 1 prior to dosing and 1 hour (r 5 min) postdosing;  
x At Week 4 prior to dosing, 1 hour (r 5 min) postdosing, and 4 hours (r 10 min) postdosing;  
x At Week 8 prior to dosing;  
x At Week 12 anytime (no study treatment administration at this visit).  
x At ET visit anytime (if ET visit is planned before Week 12 visit). 
NDI-034858 plasma concentration reported as below the limit of quantification (BLQ) will be set 
to LLOQ/2 except in the listing. Samples with no reportable value will be set to “Missing”.   
Descriptive statistics (including the coefficient of variation, geometric mean and geometric mean’s 
coefficient of variation) of the NDI-034858 plasma concentration data will be summarized based 
on nominal timepoints per dose level and will be presented in a table using the PK analysis set. 
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NDI-034858 plasma concentration data, including actual sampling time, will be listed per subject 
by visit and time points using the PK analysis set. 
11 
 
. 
 
12 CHANGES FROM ANALYSIS SPECIFIED IN THE PROTOCOL 
Changes made from the analysis specified in the protocol are the following: 
Description of the Change 
Rationale for the Change 
Continuous variables summaries will also 
present Q1 and Q3 as part of the descriptive 
statistics. 
To provide more information on descriptive 
statistics of continuous variables. 
Addition of supplementary analysis on the 
primary endpoint: Based on observed cases, 
using a logistic regression model, and based 
on the ITT analysis set. 
To study the robustness of the conclusion 
from the primary endpoint analysis.  
Any subject’s assessment collected on the day 
of the start of a prohibited medication or after 
which was adjudicated as major protocol 
deviation (Appendix 3) will be set as missing 
(for continuous endpoints) and non-responder 
(for binary endpoints, including in logistic 
regression models) for the purpose of the 
efficacy analyses. 
Subjects with prohibited medication that 
could affect psoriasis condition should be 
treated as missing or non-responder (as 
applicable). 
For the primary analysis, the odds ratio and 
proportion differences will be reported and 
calculated using the MH method. 
To report and estimate the pooled odds ratios 
and proportions differences across strata. 
Normal to abnormal shift tables for vital signs 
are replaced by abnormal vital signs tables 
based on cut-off values. 
To use pre-defined criteria instead of PI 
assessment. 
 
 
 
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13 APPENDICES 
Appendix 1 
Output Conventions 
TLF will be generated using SAS® and will be displayed on letter size paper with landscape 
orientation, 1 inch margins and 9 pt Courier New font. 
The header section will comprise the sponsor’s name, the protocol number, the delivery 
description, the data cut-off date (if applicable), the TLF number, the TLF title, the analysis set, 
and the page number (Page X of Y). The footer section will include the TLF footnotes, the CRO’s 
name, the date and time of the execution of the program, related listings number (if applicable), 
and the name of the program. 
P-values equal to or above 0.001 will be reported to 3 decimal places; p-values less than 0.001 will 
be reported as “<0.001”; p-values greater than 0.999 will be reported as “>0.999”.  
The mean, median, Q1 and Q3 will be displayed to one more decimal place than the original value; 
minimum and maximum will keep the same number of decimal places as the original value; 
standard deviation, standard error and CI will be displayed to two more decimal places than the 
original value. If derived parameters are to be summarized, the number of decimals of the derived 
values is to be chosen on a case-by-case basis, but the rule above applies. 
For categorical summary tables, percentages will be reported to one decimal place. Percentages 
between 0 and 0.1 (both exclusive) will be displayed as “<0.1”. The denominator for each 
percentage will be the number of subjects within the analysis set per treatment group unless 
otherwise specified. 
Listings will be ordered by treatment group, subject number, date and visit (where applicable). 
Nominal visit will be presented in the listings. Imputed dates will not be presented in the listings.  
Dates & Times Format 
Date and time (if available) will be presented in the format yyyy-mm-dd/hh:mm. 
 
 
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Appendix 2
Algorithm for Imputation of Start/End Date of Adverse Events
and 
Prior/Concomitant Medications
Event Start Date Imputation
x
Imputation of event end date should be done before imputation of event start date. 
x
Completely missing: Impute to the first study treatment date. 
x
Missing day and month: Impute to January 1st, unless year is the same as year of first study 
treatment dose date then impute to the first study treatment date. 
x
Missing day: Impute to the 1st of the month, unless month and year are the same as month 
and year of first study treatment dose date then impute to the first study treatment date. 
x
If imputed event start date is after event end date (imputed or not), set the event start date 
to the imputed event end date.
Event End Date Imputation
x
Completely missing (and not flagged as “ongoing”): Impute to the last contact date.
x
Missing day and month: Impute to December 31st, unless year is the same as last contact 
date then impute to the last contact date.
x
Missing day: Impute to the last day of the month, unless year and month are the same as 
year and month of last contact date then impute to the last contact date.
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Appendix 3
Major Protocol Deviation
Eligibility Deviations:
x
Participants with a diagnosis of plaque psoriasis for < 6 months
x
Body mass index (BMI) not within 18-42 kg/m2 or total body weight ≤ 50 kg (110 lb.)
x
Participant with psoriatic plaques cover < 10% of body surface area (BSA) at screening
or Day 1
x
Participant with PASI score < 12 or sPGA < 3 at screening or Day 1
x
Diagnosis of non-plaque psoriasis
Incorrect dosing:
x
Participants who receive treatment different than randomized group
x
Participants taking less than 80% or more than 120% of the planned medication during
the entire treatment period, based on calculated compliance
x
Randomized participants who do not take any blinded study medication for ≥ two
consecutive weeks
x
Restricted and Prohibited medications (refer to Protocol Section 6.4.2):
x
Participants receiving the following prohibited concomitant treatments while on study
therapy:
o
Therapeutic agent targeting IL-12, IL-17, and/or IL-23 (eg, ustekinumab,
secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab,
risankizumab)
o
Rituximab or other immune-cell depleting agents
o
Any marketed or investigational biological agent (except those listed above)
o
Systemic treatment that could affect psoriasis (including oral, intravenous,
intramuscular, intraarticular, intrathecal, or intralesional corticosteroids; oral
retinoids; immunosuppressive/immunomodulating medication; methotrexate;
cyclosporine; oral JAK inhibitors; or apremilast)
o
PUVA treatment, UV-B phototherapy (including tanning beds), or excimer laser,
or tanning booths
o
Topical medication used for psoriasis (including corticosteroids, retinoids,
vitamin D analogues [such as calcipotriol], JAK inhibitors, or tar)
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